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Ferrari C, Niccoli Asabella A, Merenda N, et al.
Pediatric Hodgkin Lymphoma: Predictive value of interim 18F-FDG PET/CT in therapy response assessment.
Medicine (Baltimore). 2017; 96(5):e5973 [PubMed] Free Access to Full Article Related Publications

We investigated the prognostic value of interim F-FDG PET/CT (PET-2) in pediatric Hodgkin lymphoma (pHL), evaluating both visual and semiquantitative analysis.Thirty pHL patients (age ≤16) underwent serial F-FDG PET/CT: at baseline (PET-0), after 2 cycles of chemotherapy (PET-2) and at the end of first-line chemotherapy (PET-T). PET response assessment was carried out visually according to the Deauville Score (DS), as well as semiquantitatively by using the semiquantitative parameters reduction from PET-0 to PET-2 (ΔΣSUVmax0-2, ΔΣSUVmean0-2). Final clinical response assessment (outcome) at the end of first-line chemotherapy was the criterion standard, considering patients as responders (R) or nonresponders (NR). Disease status was followed identifying patients with absence or relapsed/progression disease (mean follow-up: 24 months, range 3-78).Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of visual and semiquantitative assessment were calculated; furthermore, Fisher exact test was performed to evaluate the association between both visual and semiquantitative assessment and outcome at the end of the first-line chemotherapy. The prognostic capability of PET-2 semiquantitative parameters was calculated by ROC analysis and expressed as area under curve (AUC). Finally, progression-free survival (PFS) was analyzed according to PET-2 results based on the 5-point scale and semiquantitative criteria, using the Kaplan-Meier method.Based on the outcome at the end of first-line chemotherapy, 5 of 30 patients were NR, the remnant 25 of 30 were R. Sensitivity, specificity, PPV, NPV, and accuracy of visual analysis were 60%,72%,30%,90%,70%; conversely, sensitivity, specificity, PPV, NPV, and accuracy of semiquantitative assessment were 80%, 92%, 66.7%, 95.8%, 90%. The highest AUC resulted for ΔΣSUVmax0-2 (0.836; cut-off <12.5; sensitivity 80%; specificity 91%). The association between ΔΣSUVmax0-2 and outcome at the end of first-line chemotherapy resulted to have a strong statistical significance (P = 0.0026). Both methods demonstrated to influence PFS, even if the semiquantitative assessment allowed a more accurate identification of patients with a high risk of treatment failure (P = 0.005).Our preliminary results showed that PET-2 visual assessment, by using Deauville criteria, can be improved by using the semiquantitative analysis. The SUV max reduction (ΔΣSUVmax0-2) evaluation might provide a support for the interpretation of intermediate scores, predicting with good confidence those patients who will have a poor outcome and require alternative therapies.

Cho BB, Kelting SM, Gru AA, et al.
Cyclin D1 expression and polysomy in lymphocyte-predominant cells of nodular lymphocyte-predominant Hodgkin lymphoma.
Ann Diagn Pathol. 2017; 26:10-15 [PubMed] Related Publications

Cyclin D1 protein expression in lymphocytes is classically associated with mantle cell lymphoma. Although increasingly recognized in other lymphoproliferative disorders, cyclin D1 expression and CCND1 gene abnormalities have not been well studied in nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). Using a double stain for CD20/cyclin D1, we quantified cyclin D1 expression in 10 cases of NLPHL and correlated those findings with SOX11 expression, CCND1 gene abnormalities, and clinical data. For comparison, we examined 5 cases of T cell-/histiocyte-rich large B-cell lymphoma (THRLBCL). All cases of NLPHL stained for cyclin D1 showed at least rare positivity in lymphocyte-predominant (LP) cells. In 4 cases, at least 20% of LP cells were positive for CD20/cyclin D1. Neither SOX11 expression nor CCND1 gene rearrangement was found in any of the cases, but fluorescence in situ hybridization showed a proportion of the large cells with 3 to 4 copies of nonfused IGH and CCND1 signals or 3 intact CCND1 break-apart signals. Further study with CCND1/CEP11 showed polysomy in 6 of 9 cases with cyclin D1 expression and 5 of 16 NLPHL not examined for cyclin D1. Two of 5 cases of THRLBCL showed rare positive staining for CD20/cyclin D1; 1 case showed polysomy with CCND1/CEP11. Results show that cyclin D1 may be expressed in LP cells without SOX11 expression or CCND1 translocation. Polysomy with increased copies of CCND1 may account for cyclin D1 expression in some cases. Cyclin D1 expression is not useful for distinguishing NLPHL from THRLBCL and has no apparent clinical significance in NLPHL.

Related: FISH Mantle Cell Lymphoma BCL1 Gene (CCND1)

Hussain A, Tandon A, Prayaga AK, et al.
Cytomorphology and Histology Correlation of Rosai-Dorfman Disease: A 15-Year Study from a Tertiary Referral Centre in South India.
Acta Cytol. 2017; 61(1):55-61 [PubMed] Related Publications

OBJECTIVES: Rosai-Dorfman disease (RDD) is an uncommon, benign histiocytic disorder of unknown etiology, typically presenting in young adulthood. We highlight the cytomorphology of RDD and correlate it with the histopathology.
STUDY DESIGN: All cases diagnosed as RDD on fine-needle aspiration cytology between January 2001 and June 2015 were included. Clinical details were obtained from medical records. The cytology smears were reviewed along with the histopathology and immunohistochemistry, wherever available.
RESULTS: The study included 10 cases ranging in age from 11 to 68 years (median 29). There was a male predominance with a male:female ratio of 1.5:1. The patients commonly presented with bilateral cervical lymphadenopathy. Extranodal involvement was seen in 2 cases in the nose and mandible, respectively. Of these 10 cases, 8 were later biopsied. The cytological features included numerous crescentic histiocytes, emperipolesis, reactive lymphocytes and plasma cells. A histological diagnosis of RDD was made in 7 out of 8 cases, and 1 was diagnosed as Hodgkin lymphoma.
CONCLUSION: FNA represents an efficient, minimally invasive, cost-effective and reliable technique for the diagnosis of RDD and may obviate the need for further biopsy. However, the disease has close differential diagnoses, including Langerhans cell histiocytosis, granulomatous lesions, and Hodgkin lymphoma. Hence, it must be remembered that there can be pitfalls when the diagnosis is made by cytology alone.

Related: Langerhan's Cell Histiocytosis

Bur H, Haapasaari KM, Turpeenniemi-Hujanen T, et al.
Strong KDM4B and KDM4D Expression Associates with Radioresistance and Aggressive Phenotype in Classical Hodgkin Lymphoma.
Anticancer Res. 2016; 36(9):4677-83 [PubMed] Related Publications

BACKGROUND: Epigenetic regulators, including Jumonji domain 2 (JMJD2/KDM4) proteins are involved in post-translational modification of histone demethylation and have a major role in carcinogenesis of many solid tumors.
MATERIALS AND METHODS: We assessed immunohistochemically the expression of lysine (K)-specific demethylase 4 (KDM4)A, KDM4B and KDM4D in tumors from 91 patients of adriamycin, bleomycin, vinblastine, darcabazine (ABVD)-treated classical Hodgkin lymphoma.
RESULTS: Strong cytoplasmic KDM4B expression in the reactive cellular infiltrate and also in Reed-Sternberg (RS) cells predicted poor relapse-free survival (RFS) (p=0.020 and p=0.022, respectively) in patients with limited-stage disease. Strong KDM4B expression in RS cells was also related to B-symptoms (p=0.007) and advanced stage (p=0.024). Strong KDM4D expression in the cytoplasm of RS cells was also associated with poor RFS in limited-stage patients RFS (p=0.043) and, most significantly, in patients receiving involved-field radiotherapy (p=0.007).
CONCLUSION: KDM4B and KDM4D expression may associate with an aggressive subtype of classical Hodgkin lymphoma and be linked with radioresistance.

Related: Bleomycin Dacarbazine Doxorubicin Vinblastine

Afaq A, Fraioli F, Sidhu H, et al.
Comparison of PET/MRI With PET/CT in the Evaluation of Disease Status in Lymphoma.
Clin Nucl Med. 2017; 42(1):e1-e7 [PubMed] Related Publications

PURPOSE: The primary aim was to compare the diagnostic performance of PET/MRI (performed with basic anatomical MRI sequences) in detecting sites of disease in adult patients with lymphoma compared with the current standard of care, PET/CT. Secondary aims were to assess the additional value of diffusion-weighted imaging to PET/MRI in disease detection and to evaluate the relationship between the standardized uptake value on PET/MR and the apparent diffusion coefficient on diffusion-weighted imaging.
METHODS: Sixty-eight studies in 66 consecutive patients with histologically proven Hodgkin or non-Hodgkin lymphoma were prospectively evaluated. Each patient had whole body PET/CT, followed by whole body PET/MR. Two experienced readers independently evaluated the PET/MRI studies, and two other experienced readers independently evaluated PET/CT. Site of lymphoma involvement and SUVmax at all nodal sites more avid than background liver were recorded. Readers provided stage (in baseline cases) and disease status (remission vs active disease). The apparent diffusion coefficient mean value corresponding to the most avid PET site of disease was recorded.
RESULTS: Ninety-five nodal and 8 extranodal sites were identified on both PET/CT and PET/MRI. In addition, 3 nodal and 1 extranodal sites were identified on PET/MRI. For positive lesion detection, reader agreement in PET/MR was perfect between the 2 readers and almost perfect between PET/CT and PET/MR (k > 0.978). Intermodality agreement between PET/CT and PET/MRI was also near perfect to perfect for staging/disease status k = (0.979-1.000). SUVmax from PET/CT and PET/MRI correlated significantly (Spearman rho correlation coefficient, 0.842; P < 0.001). Diffusion-weighted imaging did not alter lesion detection or staging in any case. A negative correlation was demonstrated between ADC mean and SUVmax (Spearman rho correlation coefficient r, -0.642; P < 0.001).
CONCLUSIONS: PET/MRI is a reliable alternative to PET/CT in the evaluation of patients with lymphoma. Diffusion-weighted imaging did not alter diagnostic accuracy. With comparable accuracy in detection of disease sites and added benefit of radiation dose reduction, PET/MRI has a potential to become part of routine lymphoma imaging.

Related: Non Hodgkin's Lymphoma

Stacchini A, Demurtas A, Aliberti S, et al.
Single-Tube Flow Cytometry Assay for the Detection of Mature Lymphoid Neoplasms in Paucicellular Samples.
Acta Cytol. 2016; 60(4):385-394 [PubMed] Related Publications

OBJECTIVES: Flow cytometry (FC) has become a useful support for cytomorphologic evaluation (CM) of fine-needle aspirates (FNA) and serous cavity effusions (SCE) in cases of suspected non-Hodgkin lymphoma (NHL). FC results may be hampered by the scarce viability and low cellularity of the specimens.
STUDY DESIGN: We developed a single-tube FC assay (STA) that included 10 antibodies cocktailed in 8-color labeling, a cell viability dye, and a logical gating strategy to detect NHL in hypocellular samples. The results were correlated with CM and confirmed by histologic or molecular data when available.
RESULTS: Using the STA, we detected B-type NHL in 31 out of 103 hypocellular samples (81 FNA and 22 SCE). Of these, 8 were not confirmed by CM and 2 were considered to be only suspicious. The FC-negative samples had a final diagnosis of benign/reactive process (42/72), carcinoma (27/72), or Hodgkin lymphoma (3/72).
CONCLUSIONS: The STA approach allowed obtainment of maximum immunophenotyping data in specimens containing a low number of cells and a large amount of debris. The information obtained by STA can help cytomorphologists not only to recognize but also to exclude malignant lymphomas.

Related: Non Hodgkin's Lymphoma

Shao F, Wu J, Huang Z, et al.
Serendipitous Detection of Hodgkin Lymphoma by 18F-NaF PET/CT.
Clin Nucl Med. 2016; 41(10):815-8 [PubMed] Related Publications

A 17-year-old girl underwent F-NaF PET/CT to evaluate bone pain after an accident. The images did not identify any osseous lesion. However, there was a focally increased activity in the left upper chest, which corresponded to a partially calcified soft tissue mass in the mediastinum, suggestive of malignancy. The result led to subsequent F-FDG PET/CT imaging, which demonstrated intense activity in the mediastinal mass and in multiple cervical, supraclavicular, and mediastinal lymph nodes. Hodgkin lymphoma was diagnosed histopathologically following the biopsy.

Owattanapanich W, Auewarakul CU
Intracranial Hemorrhage in Patients with Hematologic Disorders: Prevalence and Predictive Factors.
J Med Assoc Thai. 2016; 99(1):15-24 [PubMed] Related Publications

BACKGROUND: Intracranial hemorrhage (ICH) is an uncommon complication in patients with hematologic disorders although high fatality rates have been shown in these patients. At present, no epidemiological data regarding ICH in patients with hematologic disorders has been collected and/or reported in Thailand.
OBJECTIVE: The purpose of this study was to determine the incidence of ICH in hospitalized patients with hematologic disorders and to identify predictive factors associated with ICH in these patients.
MATERIAL AND METHOD: The medical records of all patients with hematologic disorders admitted to Siriraj Hospital (Bangkok, Thailand) between January 2002 and September 2011 were reviewed. Patients with ICH were identified and factors associated with ICH were investigated using a retrospective case-control design.
RESULTS: Of 9,62 patients identified with hematologic disorders, ICH was diagnosed in 106 (1.1%). The ICH rate was higher in acute myeloid leukemia (AML) patients than in patients with other hematologic malignancies (4.29% vs. 0.78%; p<0. 001) and higher in aplastic anemia (AA) patients than in patients with other benign hematologic disorders (4.00% vs. 0.97%; p<0.001). Cortical hemorrhage was the main presentation in all hematologic disorders, with a single lesion in the parietal area as the most common site. The overall mortality rate was 85% with most patients succumbing within two days of onset. The independent predictors of ICH were hyperleukocytosis and a low platelet count in AML patients, and ecchymosis, upper gastrointestinal hemorrhage, hematuria, and a low platelet count in AA patients.
CONCLUSION: AML and AA patients had the highest risk of ICH compared with other hematologic disorders and several predictive factors for ICH were identified.

Related: Aplastic Anaemia Haematological Malignancies & Realted Disorders Leukemia Acute Myeloid Leukemia (AML) Non Hodgkin's Lymphoma Thailand

Dhiab MB, Ziadi S, Saad H, et al.
Changing patterns in the Epstein-Barr virus (EBV)and Hodgkin lymphoma association in Tunisia.
Ann Hematol. 2016; 95(9):1537-43 [PubMed] Related Publications

We compared the features of the Epstein-Barr virus (EBV) and Hodgkin lymphoma (HL) association in Tunisia in two periods of time, 1991-2001 (111 cases) and 2002-2012 (122 cases). The investigation of the EBV status by EBER in situ hybridization showed a significant decrease in the prevalence of EBV-positive HL from 69.3 % for the period 1991-2001 to 40.1 % for the 2002-2012 period (p = 0.00001). EBV positivity has decreased in all age groups but was more pronounced among young patients, in the 15-24-year age group (46.1 vs 10.3 %, p = 0.003), in the 25-34-year age group (56.2 vs 25 %, p = 0.04), and among children (88.4 vs 59.2 %, p = 0.01). This decrease in EBV-positive HL over time contrasted with a remarkable increase in EBV-negative HL in young adults aged 15-34 years (51.2 vs 83 %; p = 0.001), especially among women (59.1 vs 91.2 %; p = 0.01). The decrease in EBV-positive HL over time concerns particularly the nodular sclerosis histological subtype (69.2 vs 31.6 %, p = 0.000001). These results indicate that the epidemiology of HL and its association with EBV are changing over time, with a trend toward a Western profile, and point toward the emergence of other environmental causative factors, especially among young women, which remain to be identified.

Akhtar S, Rauf SM, Elhassan TA, Maghfoor I
Outcome analysis of high-dose chemotherapy and autologous stem cell transplantation in adolescent and young adults with relapsed or refractory Hodgkin lymphoma.
Ann Hematol. 2016; 95(9):1521-35 [PubMed] Related Publications

High-dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT) can salvage many patients with relapsed or refractory Hodgkin's lymphoma (HL). We are reporting the outcome of HDC auto-SCT and the impact of 21 prognostic factors in relapsed and refractory adolescent (14-21 years) and young adult (>21-30 years) (AYA) HL patients. We used Fine and Gray's competing risk analysis method and regression model for outcome analysis. From 1996 to 2013, 290 consecutive patients with biopsy-proven HL underwent HDC auto-SCT for relapsed/refractory HL; 216 patients (74.5 %) were AYA at the time of auto-SCT. Male/female were equal, median age at auto-SCT was 22.4 years, and there were 94 adolescent (43.5 %) and 122 young adults (56.5 %). There was refractory disease in 121 (56 %) patients, relapsed in 95 (44 %). Median follow-up was 72.6 months. The Kaplan-Meier method estimated that 5-year overall survival is 62.7 % (adolescents (63.5 %), young adults (62 %)) and event-free survival was 51.3 %. Five-year cumulative incidence of disease-specific death (DS-death) is 33 % and that of DS-event is 45 %. For DS-death, the multivariate analysis identified complete remission (CR) duration of <12 months (hazard ratio (HR) 3.61, P = 0.0009), no CR after salvage (HR: 3.93, P = 0.0002), and nodular sclerosis pathology (HR 3.3, P = 0.016) and positive B symptoms (HR 2, P = 0.028) as negative factors. For DS-event, CR duration of <12 months (HR 1.88, P = 0.02), no CR after salvage (HR 3.47, P = 0.000005) and nodular sclerosis pathology (HR 1.88, P = 0.02) were found significant. The Kaplan-Meier method estimated overall survival (OS) at 36 months with 0-2:3:4 factors being 93.6:54:21 %, respectively (P value <0.001). Kaplan-Meier estimated event-free survival (EFS) at 36 months with 0-1:2:3 factors being 84.6:65:31 %, respectively (P value <0.001). Clinically, adolescents have similar outcomes as young adults.

Tatci E, Biner IU, Tanyildiz HG, et al.
18F-FDG PET/CT Imaging of Hodgkin Lymphoma in a Child with Common Variable Immunodeficiency.
J Nucl Med Technol. 2016; 44(4):259-260 [PubMed] Related Publications

Common variable immunodeficiency is characterized by low levels of serum immunoglobulins and antibodies, recurrent infections, and a predisposition to malignancy. Here, we present the (18)F-FDG PET/CT findings of a 7-y-old boy with common variable immunodeficiency and Hodgkin lymphoma.

Caocci G, Greco M, Fanni D, et al.
HLA-G expression and role in advanced-stage classical Hodgkin lymphoma.
Eur J Histochem. 2016; 60(2):2606 [PubMed] Free Access to Full Article Related Publications

Non-classical human leucocyte antigen (HLA)-G class I molecules have an important role in tumor immune escape mechanisms. We investigated HLA-G expression in lymphonode biopsies taken from 8 controls and 20 patients with advanced-stage classical Hodgkin lymphoma (cHL), in relationship to clinical outcomes and the HLA-G 14-basepair (14-bp) deletion-insertion (del-ins) polymorphism. Lymphnode tissue sections were stained using a specific murine monoclonal HLA-G antibody. HLA-G protein expression was higher in cHL patients than controls. In the group of PET-2 positive (positron emission tomography carried out after 2 cycles of standard chemotherapy) patients with a 2-year progression-free survival rate (PFS) of 40%, we observed high HLA-G protein expression within the tumor microenvironment with low expression on Hodgkin and Reed-Sternberg (HRS) cells. Conversely, PET-2 negative patients with a PFS of 86% had higher HLA-G protein expression levels on HRS cells compared to the microenvironment. Lower expression on HRS cells was significantly associated with the HLA-G 14-bp ins/ins genotype. These preliminary data suggest that the immunohistochemical pattern of HLA-G protein expression may represent a useful tool for a tailored therapy in patients with cHL, based on the modulation of HLA-G expression in relation to achievement of negative PET-2.These preliminary data suggest that the immunohistochemical pattern of HLA-G protein expression may represent a useful tool for a tailored therapy in patients with cHL, based on the modulation of HLA-G expression in relation to achievement of negative PET-2.

Johnson P, Federico M, Kirkwood A, et al.
Adapted Treatment Guided by Interim PET-CT Scan in Advanced Hodgkin's Lymphoma.
N Engl J Med. 2016; 374(25):2419-29 [PubMed] Free Access to Full Article Related Publications

BACKGROUND: We tested interim positron-emission tomography-computed tomography (PET-CT) as a measure of early response to chemotherapy in order to guide treatment for patients with advanced Hodgkin's lymphoma.
METHODS: Patients with newly diagnosed advanced classic Hodgkin's lymphoma underwent a baseline PET-CT scan, received two cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy, and then underwent an interim PET-CT scan. Images were centrally reviewed with the use of a 5-point scale for PET findings. Patients with negative PET findings after two cycles were randomly assigned to continue ABVD (ABVD group) or omit bleomycin (AVD group) in cycles 3 through 6. Those with positive PET findings after two cycles received BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone). Radiotherapy was not recommended for patients with negative findings on interim scans. The primary outcome was the difference in the 3-year progression-free survival rate between randomized groups, a noninferiority comparison to exclude a difference of 5 or more percentage points.
RESULTS: A total of 1214 patients were registered; 937 of the 1119 patients (83.7%) who underwent an interim PET-CT scan according to protocol had negative findings. With a median follow-up of 41 months, the 3-year progression-free survival rate and overall survival rate in the ABVD group were 85.7% (95% confidence interval [CI], 82.1 to 88.6) and 97.2% (95% CI, 95.1 to 98.4), respectively; the corresponding rates in the AVD group were 84.4% (95% CI, 80.7 to 87.5) and 97.6% (95% CI, 95.6 to 98.7). The absolute difference in the 3-year progression-free survival rate (ABVD minus AVD) was 1.6 percentage points (95% CI, -3.2 to 5.3). Respiratory adverse events were more severe in the ABVD group than in the AVD group. BEACOPP was given to the 172 patients with positive findings on the interim scan, and 74.4% had negative findings on a third PET-CT scan; the 3-year progression-free survival rate was 67.5% and the overall survival rate 87.8%. A total of 62 patients died during the trial (24 from Hodgkin's lymphoma), for a 3-year progression-free survival rate of 82.6% and an overall survival rate of 95.8%.
CONCLUSIONS: Although the results fall just short of the specified noninferiority margin, the omission of bleomycin from the ABVD regimen after negative findings on interim PET resulted in a lower incidence of pulmonary toxic effects than with continued ABVD but not significantly lower efficacy. (Funded by Cancer Research UK and Others; ClinicalTrials.gov number, NCT00678327.).

Related: Bleomycin Dacarbazine Doxorubicin Vinblastine

Toto RL, Zuckerbraun NS, Manole MD
Neck Pain in a 12-Year-Old Female: An Unusual Diagnosis.
J Emerg Med. 2016; 51(2):e15-8 [PubMed] Related Publications

BACKGROUND: Neck pain in the pediatric population has a broad differential diagnosis, ranging from benign to imminently life-threatening causes. Trauma and infection represent the most common etiologies of pediatric neck pain in the pediatric emergency department (PED) setting. Malignancy, though a rare cause of pediatric neck pain, is important to consider in patients with acquired torticollis or focal neurologic signs.
CASE REPORT: We describe the case of a previously healthy 12-year-old female who presented to the PED with neck pain radiating down her upper extremities. The physical examination revealed diminished strength in her upper extremities compared to her lower extremities. Further evaluation revealed lymphadenopathy in the cervical and mediastinal areas and an epidural tumor in the cervical spinal column. The ultimate diagnosis was Hodgkin lymphoma presenting in an unusual manner with cervical spinal cord compression. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Neck pain is a common chief complaint among pediatric patients in the emergency setting. This case of spinal cord compression caused by malignancy illustrates the necessity of detailed spinal imaging in patients with neck pain and "red flag" signs, including but not limited to an abnormal neurologic examination.

Annunziata S, Cuccaro A, Calcagni ML, et al.
Interim FDG-PET/CT in Hodgkin lymphoma: the prognostic role of the ratio between target lesion and liver SUVmax (rPET).
Ann Nucl Med. 2016; 30(8):588-92 [PubMed] Related Publications

OBJECTIVE: To evaluate the prognostic role of the ratio between target lesion and liver SUVmax (rPET) in patients with Hodgkin lymphoma (HL) undergoing interim FDG-PET/CT and to compare rPET with the 5-point Deauville Score (5p-DS).
METHODS: Sixty-eight patients with HL undergoing interim FDG-PET/CT after first courses of chemotherapy were evaluated. The receiver operating characteristic (ROC) approach was applied to identify the optimal cutpoint of rPET with respect to progression free survival (PFS). The prognostic significance of rPET was compared with 5p-DS (scores 4 and 5 considered as positive). Positive predictive value (PPV) and negative predictive value (NPV) were calculated using the presence of an adverse event as the gold standard.
RESULTS: The ROC analysis for rPET as a predictor of progression showed an optimal rPET cutpoint of 1.14. Both 5p-DS and rPET were strong outcome predictors (p < 0.001). Patients with negative 5p-DS and patients with rPET <1.14 had a similar two-year PFS (86 and 87 %, respectively). Patients with a positive 5p-DS had a 2-year PFS of 27 %, while patients with rPET >1.14 had a 2-year PFS of 15 %. 5p-DS and rPET cutoff of 1.14 showed a PPV of 58 versus 70 %, and a NPV of 85 versus 86 %, respectively.
CONCLUSIONS: rPET could be considered an accurate prognostic factor in patients with HL undergoing interim FDG-PET/CT. Larger prospective studies are needed to confirm these data.

Sultan S, Irfan SM, Parveen S, et al.
Frequency and Pattern of Bone Marrow Infiltration in Classical Hodgkin's Lymphoma: Experience from Southern Pakistan.
Asian Pac J Cancer Prev. 2016; 17(4):1857-9 [PubMed] Related Publications

BACKGROUND: Hodgkin's lymphoma (formerly, Hodgkins disease) is a potentially curable malignancy with distinctive biological behavior and specific clinical characteristics. Limited information is available from developing countries for patients with classical Hodgkin's lymphoma (cHL). Therefore we reviewed the demographical and clinico-hematological profiles along with bone marrow infiltration patterns in adult patients presenting at Liaquat National Hospital and Medical College.
MATERIALS AND METHODS: In this cross sectional study, 62 adult (≥15 years) patients with cHL were enrolled from January 2010 to December 2014.
RESULTS: The mean age was 29.7±13.8 years with a median of 30 years. The male to female ratio was 2:1. B symptoms were present in 72.5% of patients and lymph node enlargement in 85.4%. The frequency of bone marrow infiltration in our cHL patients was found to be 27.4%, the pattern being predominantly focal followed by diffuse. The mean hemoglobin was 9.4±1.9g/dl with a mean MCV of 78.1±7.9 fl, a mean total leukocyte count of 10.9±20.6x109/l and a mean platelet count of 241.6±150.1x109/l.
CONCLUSIONS: Our analysis shows that clinico-pathological features of cHL in Pakistan are comparable to published data. Peripheral lymphodenopathy associated with B symptoms is the commonest presentation. Bone marrow involvement is more common in our setup as patients usually presented at an advanced stage of disease.

Büyükkapu-Bay S, Çorapçıoğlu F, Aksu G, et al.
Prognostic factors and treatment results of pediatric Hodgkin's lymphoma: A single center experience.
Turk J Pediatr. 2015 Jul-Aug; 57(4):359-66 [PubMed] Related Publications

The aim of this study was to assess the demographic, clinic data, prognostic factors and treatment/follow-up results of children who were diagnosed with Hodgkin lymphoma and followed in our center of Pediatric Oncology, Kocaeli University Medical Faculty, Kocaeli, Turkey, for 10 years. This retrospective study evaluated 41 patients with Hodgkin lymphoma who were younger than 18 years-old. All patients were treated with risked adapted ABVD (Adriamycin, Bleomycin, Vincristine, Dacarbazine) chemotherapy and also received involved field radiotherapy. Thirty-two patients (78%) were males and 9 (22%) were females, with a mean age of 10.7±4.0 years. The histopathological diagnosis was mixed cellular type in 51.2% of the patients. B symptoms (unexplained fever, unexplained weight loss, drenching night sweats) were present in 53.7% of the patients and 36.6% of the patients were at advanced stage at the time of the diagnosis. The 3-year overall and event-free survival rates were 88% and 5-year overall and event-free survival rates were 88%, 78%. Age, stage, treatment risk groups, presence of B symptoms and hematological parameters had no significant effect on overall and event-free survival in univariate analysis while bulky disease was the only significant factor on overall survival. Our treatment policy was succesful regarding the similar survival rates in the treatment risk groups, however novel treatment strategies adopting the early response with the reduction of adverse effects are planned in the near future.

Related: Bleomycin Dacarbazine Doxorubicin Vinblastine

Ibrahim T, Chehab G, Saliba Z, et al.
PULMONARY ARTERY ACCELERATED FLOW REVEALING HODGKIN'S LYMPHOMA.
J Med Liban. 2016 Jan-Mar; 64(1):58-9 [PubMed] Related Publications

We present a case in which transthoracic echocardiography was the first diagnostic tool to suspect mediastinal Hodgkin's lymphoma by revealing a change in the hemodynamic of left pulmonary artery flow, and it was used as a follow-up method for monitoring treatment efficacy by demonstrating a normalization of pulmonary artery hemodynamics.

Alex-Okoro J, Orji FT, Umedum NG, Akpeh JO
The comparison of the pathological data of oropharyngeal masses between HIV and non-HIV patients.
Acta Otolaryngol. 2016; 136(9):969-72 [PubMed] Related Publications

CONCLUSION: Although this study did not show higher risk of oropharyngeal malignancy in HIV patients overall, they still had much higher prevalence of NHL as well as HL than HIV negative patients. Presence of cervical lymphadenopathy is unreliable in differentiating malignant oropharyngeal tumours from benign lymphoid hyperplasia in HIV patients.
OBJECTIVES: The aim of this study was to compare the histology of oropharyngeal masses between HIV positive and negative patients.
METHODS: A retrospective review of 119 patients who underwent oropharyngeal biopsies in a tertiary institution between 2007-2014 and whose HIV status was known (HIV positives =47; negatives =72).
RESULTS: Malignancies occurred in 63.8% of HIV patients and 65% of the negative group (p = 0.87). While non-Hodgkin's lymphoma (NHL), squamous cell carcinoma (SCC), and Hodgkin's lymphoma (HL) constituted 40%, 27%, and 17% of malignancies in HIV patients, respectively; in the HIV-negative group, it was 53%, 13%, and 2% for SCC, NHL, and HL, respectively (p = 0.039, 0.017, and 0.035, respectively). Reactive lymphoid proliferation accounted for 82.4% of the benign masses in the HIV positive group. Malignant tumours were recorded more in younger patient in the HIV positive than the negative group (p = 0.001).

Related: Non Hodgkin's Lymphoma Childhood Non-Hodgkin's Lymphoma NHL - Molecular Biology Oropharyngeal Cancer

Aurer I, Nemet D, Mitrović Z, et al.
High-dose ifosfamide and mitoxantrone (HDIM) in patients with relapsed or refractory Hodgkin's lymphoma.
Ann Hematol. 2016; 95(7):1129-36 [PubMed] Related Publications

Relapsed/refractory Hodgkin's lymphoma (HL) is treated with salvage chemotherapy and autologous stem cell transplantation (ASCT). Optimal chemotherapy is unknown. We retrospectively analyzed outcomes of 58 patients treated with 2 cycles of high-dose ifosfamide and mitoxantrone (HDIM). HDIM consisted of ifosfamide 5 g/m(2)/day and MESNA 5 g/m(2)/day in continuous 24-h infusion (days 1 and 2), MESNA 2.5 g/m(2) over 12 h (day 3), and mitoxantrone 20 mg/m(2) (day 1) administered every 2 weeks. Stem cells were collected after the first cycle. Responding patients proceeded to ASCT. Toxicity was acceptable. Stem cell mobilization was successful in 96 % of patients. Overall response rate was 74 % (89 % in relapsing and 45 % in refractory patients) with 31 % complete remissions. After a median follow-up of 54 months, 5-year event-free survival was 56 % (69 % for relapsing and 35 % for refractory patients), and 5-year overall survival was 67 % (73 % for relapsing and 55 % for refractory patients). Significant adverse prognostic factors were refractoriness to previous therapy and HDIM failure. No differences in outcomes were noted between patients with early and late relapses or between complete and partial responders. HDIM is a well-tolerated and effective regimen for relapsed and refractory HL with excellent stem cell mobilizing properties. Patients failing HDIM may still benefit from other salvage options.

Related: Ifosfamide Mitoxantrone

Bhatt VR, Giri S, Verma V, et al.
Secondary acute myeloid leukemia in survivors of Hodgkin lymphoma.
Future Oncol. 2016; 12(13):1565-75 [PubMed] Related Publications

BACKGROUND: This large population-based study determined the epidemiology and outcomes of secondary acute myeloid leukemia (sAML) developing in Hodgkin lymphoma survivors.
METHODS: We utilized the Surveillance Epidemiology and End Results (SEER) 9 database to identify 104 cases of sAML.
RESULTS: Patients with sAML (median age: 47 years; 82% <60 years) were significantly younger than de novo AML cases (66 years; p < 0.01). sAML had worse overall survival (OS) than de novo AML (p < 0.01). OS was better in younger patients and in more recent years.
CONCLUSION: Older patients with sAML have a dismal OS and should be enrolled in trials of novel therapies. Younger patients have improved OS and hence may benefit from curative intent intensive therapy and allogeneic transplant.

Related: Acute Myeloid Leukemia (AML)

La Nasa G, Greco M, Littera R, et al.
The favorable role of homozygosity for killer immunoglobulin-like receptor (KIR) A haplotype in patients with advanced-stage classic Hodgkin lymphoma.
J Hematol Oncol. 2016; 9:26 [PubMed] Free Access to Full Article Related Publications

BACKGROUND: Interim positron emission tomography after 2 cycles of ABVD (iPET-2) is a good predictor of outcome in advanced-stage classic Hodgkin lymphoma. So far, there are no other prognostic biomarkers capable of identifying chemotherapy refractory patients with comparable accuracy. Despite the considerable amount of evidence suggesting that antitumor immune surveillance is downregulated in classic Hodgkin lymphoma (cHL), few data exist on the impairment of natural killer cell function and the role of their killer immunoglobulin-like receptors (KIRs).
METHODS: We investigated KIR gene frequencies, KIR haplotypes, and KIR-ligand combinations in a cohort of 135 patients with advanced-stage classic Hodgkin lymphoma and 221 healthy controls. We furthermore evaluated the correlation of KIR genes and KIR haplotypes with the achievement of negative iPET-2.
RESULTS: In the cohort of patients, the 5-year overall survival and progression-free survival were 93.6 and 79%, respectively. Homozygosity for KIR A haplotype and the HLA-C1 KIR ligand (KIR-AA/C1C1) was significantly higher in healthy controls (15.7 vs. 4.8%, p = 0.001). The KIR-AA genotype resulted to have a significant predictive power for achieving iPET-2 negativity (p = 0.039).
CONCLUSIONS: Homozygosity for KIR A haplotype offers protection against classic Hodgkin lymphoma. The association found for the KIR-AA genotype and achievement of negative iPET-2 suggests that KIR-AA could be used in clinical practice to enhance the chemosensitivity predictive power of iPET-2. Our results point to the possibility of adapting treatment strategies based on the combination of KIR biomarkers and PET scan.

Related: Bleomycin Dacarbazine Doxorubicin Vinblastine

Candela JL
CE: Cardiotoxicity and Breast Cancer as Late Effects of Pediatric and Adolescent Hodgkin Lymphoma Treatment.
Am J Nurs. 2016; 116(4):32-42; quiz 43 [PubMed] Related Publications

The American Cancer Society estimates that in 2014 nearly 16,000 U.S. children and adolescents developed cancer, and in roughly 1,200 of these cases the cancer was Hodgkin lymphoma (HL). The great majority of these patients will survive, joining the thousands who have been diagnosed and treated successfully in decades past. Nurses' familiarity with and attention to the late effects of the chemotherapy and radiation therapy used to treat HL, which include breast cancer as well as cardiotoxicity and its sequelae, are essential in helping these patients maintain their overall health.

Related: Breast Cancer USA

Kluge R, Chavdarova L, Hoffmann M, et al.
Inter-Reader Reliability of Early FDG-PET/CT Response Assessment Using the Deauville Scale after 2 Cycles of Intensive Chemotherapy (OEPA) in Hodgkin's Lymphoma.
PLoS One. 2016; 11(3):e0149072 [PubMed] Free Access to Full Article Related Publications

PURPOSE: The five point Deauville (D) scale is widely used to assess interim PET metabolic response to chemotherapy in Hodgkin lymphoma (HL) patients. An International Validation Study reported good concordance among reviewers in ABVD treated advanced stage HL patients for the binary discrimination between score D1,2,3 and score D4,5. Inter-reader reliability of the whole scale is not well characterised.
METHODS: Five international expert readers scored 100 interim PET/CT scans from paediatric HL patients. Scans were acquired in 51 European hospitals after two courses of OEPA chemotherapy (according to the EuroNet-PHL-C1 study). Images were interpreted in direct comparison with staging PET/CTs.
RESULTS: The probability that two random readers concord on the five point D score of a random case is only 42% (global kappa = 0.24). Aggregating to a three point scale D1,2 vs. D3 vs. D4,5 improves concordance to 60% (kappa = 0.34). Concordance if one of two readers assigns a given score is 70% for score D1,2 only 36% for score D3 and 64% for D4,5. Concordance for the binary decisions D1,2 vs. D3,4,5 is 67% and 86% for D1,2,3 vs D4,5 (kappa = 0.36 resp. 0.56). If one reader assigns D1,2,3 concordance probability is 92%, but only 64% if D4,5 is called. Discrepancies occur mainly in mediastinum, neck and skeleton.
CONCLUSION: Inter-reader reliability of the five point D-scale is poor in this interobserver analysis of paediatric patients who underwent OEPA. Inter-reader variability is maximal in cases assigned to D2 or D3. The binary distinction D1,2,3 versus D4,5 is the most reliable criterion for clinical decision making.

Related: Doxorubicin Etoposide Vincristine

Sonigo C, Seroka A, Cédrin-Durnerin I, et al.
History of ABVD alters the number of oocytes vitrified after in vitro maturation in fertility preservation candidates.
Future Oncol. 2016; 12(14):1713-9 [PubMed] Related Publications

AIM: This retrospective case-control study aimed at analyzing the results of in vitro maturation (IVM) of oocytes, used for fertility preservation (FP), in patients with history of ABVD (adriamycin, bleomycin, vinblastine and dacarbazine) for classical Hodgkin lymphoma.
PATIENTS & METHODS: A total of 22 candidates for FP, having received ABVD at least 2 years before IVM for FP were studied. IVM results were compared with those of 44 breast cancer patients, without history of chemotherapy, matched for ovarian reserve parameters.
RESULTS: The number of cumulo-oocyte complexes recovered and the total number of matured oocytes vitrified was lower in patients having received AVBD (5.5 ± 4.8 vs 8.5 ± 4.4 oocytes; p = 0.03 and 3.5 ± 3.7 vs 6 ± 3.0 oocytes; p < 0.04, respectively).
CONCLUSION: In light of these results, FP should be discussed before ABVD.

Related: Bleomycin Dacarbazine Doxorubicin Vinblastine

Hodgson DC, Cotton C, Crystal P, Nathan PC
Impact of Early Breast Cancer Screening on Mortality Among Young Survivors of Childhood Hodgkin's Lymphoma.
J Natl Cancer Inst. 2016; 108(7) [PubMed] Related Publications

BACKGROUND: Female survivors treated with thoracic radiation therapy (RT) for childhood cancer experience increased risks of breast cancer (BC). There are currently no data quantifying the potential mortality gains of early BC screening among such survivors.
METHODS: A mathematical model of BC development was used to evaluate the marginal benefit of early-initiated screening of female survivors of adolescent Hodgkin's lymphoma (HL) starting at age 25 years on BC mortality compared with screening initiated at age 40 years. Sensitivity analyses were performed to evaluate the robustness of the estimates over a plausible range of conditions.
RESULTS: For survivors treated at age 15 years, the absolute risk of BC mortality by age 75 years was predicted to decrease from 16.65% with no early screening to 16.28% (annual mammography), 15.40% (annual MRI), 15.38% (same-day annual mammography and MRI), and 15.37% (alternating mammography and MRI every six months). Approximately 80 patients would need to be invited to MRI-based screening to prevent one BC death. In sensitivity analyses, the number needed to invite to MRI-based screening to prevent one BC death ranged from 71 to 333. Combinations of MRI plus mammography were predicted to produce 99.52 false positives per 1000 screenings done between age 25 to 39 years.
CONCLUSIONS: These findings are the first to indicate that early MRI-based screening should reduce BC mortality among women treated with RT for adolescent HL. The magnitude of this benefit is superior to that described for other accepted screening indications although MRI can produce a substantial rate of false-positive results.

Related: Breast Cancer Cancer Screening and Early Detection

Abou-Antoun T, Mikhael R, Massoud M, et al.
Effects of Radiotherapy on the Risk of Developing Secondary Malignant Neoplasms in Hodgkin's Lymphoma Survivors.
Asian Pac J Cancer Prev. 2016; 17(2):749-54 [PubMed] Related Publications

Extended follow-up of Hodgkin lymphoma (HL) survivors indicates that these patients are at high risk of secondary malignant neoplasms (SMNs) contributing to increased morbidity and mortality. This study examined the characteristics of HL survivors who developed SMNs with the aim to report any correlation with radiotherapy (RT) dose. In this retrospective multi-center cohort study of HL patients treated between 1990 and 2011 at three major teaching hospitals in Lebanon, classification was into two groups including those treated with combined modality (RT and chemotherapy-CHT) and those treated with CHT alone. Approval from the University Institutional Review Board (IRB) was obtained. Of the 112 patients evaluated, 52.7% (59) received the combined modality while 47.3% (53) received CHT alone. There were 6 cases of SMNs in the combined modality cohort and 5 cases in the CHT cohort. The mean RT dose in the combined modality cohort was 34.5 Gray (Gy) (SD ± 5.3). A statistically significant increase (1.5 fold) in the risk of developing SMNs was observed among patients who received a dose higher than 41 Gy compared to a dose between 20 to 30 Gy (OR= 1.5; 95% confidence interval= 0.674 to 3.339, p=0.012). The risk of SMNs was not significantly higher among patients who received extended field compared to involved field RT (p=0.964). This study showed that the risk of developing SMNs is higher among patients treated with RT dose greater than 31 Gy, independent of the RT type used.

Vassilakopoulos TP, Dimopoulou MN, Angelopoulou MK, et al.
Prognostic Implication of the Absolute Lymphocyte to Absolute Monocyte Count Ratio in Patients With Classical Hodgkin Lymphoma Treated With Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine or Equivalent Regimens.
Oncologist. 2016; 21(3):343-53 [PubMed] Free Access to Full Article Related Publications

Low absolute lymphocyte count (ALC) to absolute monocyte count (AMC) ratio (ALC/AMC) is an independent prognostic factor in Hodgkin lymphoma (HL), but different cutoffs (1.1, 1.5, and 2.9) have been applied. We aimed to validate the prognostic significance of ALC/AMC in 537 homogenously treated (doxorubicin, bleomycin, vinblastine, and dacarbazine or equivalents ± radiotherapy) classical HL patients at various cutoffs. The median ALC/AMC was 2.24 (0.44-20.50). The median AMC was 0.653 × 10(9)/L (0.050-2.070). Lower ALC/AMC was associated with established markers of adverse prognosis. In total, 477 (89%), 418 (78%), and 189 (35%) patients had an ALC/AMC ratio of ≥1.1, ≥1.5, and ≥2.9; respectively; 20% had monocytosis (≥0.9 × 10(9)/L). Ten-year time to progression (TTP) was 77% versus 55% for patients with ALC/AMC ≥1.1 and <1.1 (p = .0002), 76% versus 68% for ALC/AMC ≥1.5 and <1.5 (p = .049), 77% versus 73% for ALC/AMC ≥2.9 and <2.9 (p = .35), and 79% versus 70% for ALC/AMC ≥2.24 and <2.24 (p = .08), respectively. In stages ΙΑ/ΙΙΑ and in patients ≥60 years old, ALC/AMC had no significant effect on TTP. In advanced stages, ALC/AMC was significant only at the cutoff of 1.1 (10-year TTP 67% vs. 48%; p = .016). In younger, advanced-stage patients, the differences were more pronounced. In multivariate analysis of TTP, ALC/AMC < 1.1 (p = .007) and stage IV (p < .001) were independent prognostic factors; ALC/AMC was independent of International Prognostic Score in another model. ALC/AMC was more predictive of overall survival than TTP. At the cutoff of 1.1, ALC/AMC had independent prognostic value in multivariate analysis. However, the prognostically inferior group comprised only 11% of patients. Further research is needed prior to the widespread use of this promising marker.

Related: Bleomycin Dacarbazine Doxorubicin Vinblastine

Bowen EM, Pfeiffer RM, Linet MS, et al.
Relationship between ambient ultraviolet radiation and Hodgkin lymphoma subtypes in the United States.
Br J Cancer. 2016; 114(7):826-31 [PubMed] Article available free on PMC after 29/03/2017 Related Publications

BACKGROUND: There are few modifiable risk factors for Hodgkin lymphoma (HL), the most common cancer among young adults in Western populations. Some studies have found a reduced risk with exposure to ultraviolet radiation (UVR), but findings have been inconsistent and limited to HL as a group or the most common subtypes.
METHODS: We evaluated UVR and incidence of HL subtypes using data from 15 population-based cancer registries in the United States from 2001 to 2010 (n=20 021). Ground-based ambient UVR estimates were linked to county of diagnosis. Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated for UVR quintiles using Poisson regression models adjusted for age, sex, race/ethnicity, diagnosis year, and registry.
RESULTS: Hodgkin lymphoma incidence was lower in the highest UVR quintile for nodular sclerosis (IRR=0.84, 95% CI=0.75-0.96, P-trend<0.01), mixed cellularity/lymphocyte-depleted (IRR=0.66, 95% CI=0.51-0.86, P-trend=0.11), lymphocyte-rich (IRR=0.71, 95% CI=0.57-0.88, P-trend<0.01), and nodular lymphocyte predominant HL (IRR=0.74, 95% CI=0.56-0.97, P-trend<0.01), but 'not otherwise specified' HL (IRR=1.19, 95% CI=0.96-1.47, P-trend=0.11).
CONCLUSIONS: This is the largest study of UVR and HL subtypes covering a wide range of UVR levels; however, we lack information on personal UVR and other individual risk factors. These findings support an inverse association between UVR and HL.

Related: USA

Zinzani PL, Broccoli A, Gioia DM, et al.
Interim Positron Emission Tomography Response-Adapted Therapy in Advanced-Stage Hodgkin Lymphoma: Final Results of the Phase II Part of the HD0801 Study.
J Clin Oncol. 2016; 34(12):1376-85 [PubMed] Related Publications

PURPOSE: The clinical impact of positron emission tomography (PET) evaluation performed early during first-line therapy in patients with advanced-stage Hodgkin lymphoma, in terms of providing a rationale to shift patients who respond poorly onto a more intensive regimen (PET response-adapted therapy), remains to be confirmed.
PATIENTS AND METHODS: The phase II part of the multicenter HD0801 study involved 519 patients with advanced-stage de novo Hodgkin lymphoma who received an initial treatment with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and who underwent an early ifosfamide-containing salvage treatment followed by stem-cell transplantation if they showed a positive PET evaluation after two cycles of chemotherapy (PET2). The primary end point was 2-year progression-free survival calculated for both PET2-negative patients (who completed a full six cycles of ABVD treatment) and PET2-positive patients. Overall survival was a secondary end point.
RESULTS: In all, 103 of the 512 evaluable patients were PET2 positive. Among them, 81 received the scheduled salvage regimen with transplantation, 15 remained on ABVD (physician's decision, mostly because of minimally positive PET2), five received an alternative treatment, and two were excluded because of diagnostic error. On intention-to-treat analysis, the 2-year progression-free survival was 76% for PET2-positive patients (regardless of the salvage treatment they received) and 81% for PET2-negative patients.
CONCLUSION: Patients with advanced-stage Hodgkin lymphoma for whom treatment was at high risk of failing appear to benefit from early treatment intensification with autologous transplantation, as indicated by the possibility of successful salvage treatment in more than 70% of PET2-positive patients through obtaining the same 2-year progression-free survival as the PET2-negative subgroup.

Related: Stem Cell and Bone Marrow Transplants

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