Cycles Of Adriamycin, Bleomycin, Vinblastine, Dacarbazine Research Articles

Role of Interim PET Scan after 2 Cycles of ABVD in Pediatric Hodgkin Lymphoma: Retrospective Multicenter Study from South India

Abstract Introduction Most Indian centers use Adriamycin/Bleomycin/Vinblastine/Dacarba-zine (ABVD) chemotherapy for pediatric Hodgkin lymphoma (pHL). To reduce the late toxicity, robust predictive markers are needed to risk stratify pHL patients, thereby limiting the number of chemotherapy cycles and omitting radiation for low-risk and intensifying treatment for high-risk children. Objective This study was conducted to analyze the outcome of pHL patients treated with ABVD and various factors predicting the outcome. Materials and Methods This retrospective study analyzed the outcome of 113 consecutive pHL children treated with ABVD chemotherapy from 11 tertiary care centers in South India from 2009 to 2019. Results The median duration of follow-up was 2.73 years. The median age was 13 years. B symptoms are seen in 50.5% patients, bulky disease in 23%, and stage IV in 28.3%. Of 113 pHL, 69% had a positron emission tomography (PET) and 31% had computed tomography (CT)-based staging. Stage IV (37.1%) and extranodal involvement (31.2%) were seen more often with PET than with CT staging (8.5 and 2.8%, respectively). Among 64 patients with interim PET scan after two cycles (iPET2), 20.3% did not achieve complete remission (CR) and no factors were significantly associated. The 4-year event-free survival (EFS) rate of the entire cohort was 86%. The 4-year EFS rate was 93% for patients with CR in iPET2 and 52% for patients not achieving CR. The only independent predictor of low EFS was iPET2 response (p < 0.05). Conclusion Our study confirms the prognostic role of PET scan staging and response assessment. Not achieving CR on the iPET2 scan indicates poor prognosis and warrants clinical trial enrollment for a better outcome.

Adolescent and Young Adult Hodgkin Lymphoma: Is More Better?

Background: There is a lack of a uniform approach in the treatment of Classical Hodgkin lymphoma (CHL) in adolescents and young adults (AYA). Age cutoffs are arbitrary and based on institutional experience. Chemotherapy using ABVD (Adriamycin Bleomycin Vinblastine Dacarbazine) is the standard of care in most centers for the management of adult CHL. Children and adolescents have been managed with more chemo intense approaches like the EURONET protocol, with better Event-free survival (EFS) outcomes while reducing the need for radiation therapy (RT). There is a knowledge gap regarding the optimum treatment in the AYA group and this pertains to strategies to improve EFS while addressing increasing concerns of acute toxicities and long-term complications of therapy, RT especially. We share the retrospective experience of our center where young adults and adolescents received two different strategies based on an age cutoff alone, resulting in different outcomes. Methodology: A retrospective chart review of patients aged 10-30 years with newly diagnosed CHL between January 2014 to Dec, 2019 was undertaken. The demographic and clinical profile, treatment details, treatment related complications, RT requirement, and follow-up status for the entire cohort and for each of ABVD and EURONET treatment subsets were analysed. EURONET treatment strategy used 2 cycles of OEPA (Vincristine + Etoposide + Prednisone + Adriamycin) followed by 1-4 cycles of COPDAC (Cyclophosphamide + Vincristine + Dacarbazine + Prednisone), based on the risk level. ABVD protocol used 2 cycles of ABVD followed by 2 - 4 cycles of AVD/ABVD, or intensified chemotherapy based on the interim PET-CT scan response. RT was reserved for inadequate responders during interim assessment in both protocols. Events calculated were death, progression, refractory disease and relapse. Results: 470 patients with CHL were registered at our centre in the study period. 156 patients were in the 10-30yrs age group. 30 adolescents between ≥10 and <18 years of age (with median age 15.9 years) received the EURONET treatment strategy and 126 patients between ≥18 and ≤30 years (median age 22.7 years) received ABVD protocol. Median follow-up for the entire cohort was 28 months. The patient characteristics are shown in the Table 1. Advanced disease (Stage IIB-IV, and Bulky disease) was seen in 67.4% and 63.3% of patients treated with ABVD and EURONET treatment protocols, respectively. RT was administered in 37.7% of the patients on ABVD and 3.3 % patients on EURONET treatment protocol (Figure 1). 23% of the patients receiving the ABVD therapy had an event compared to 3.3% of the patients in the EURONET treatment group. The EURONET treatment group experienced more grade 3 or 4 acute toxicities (46.6%) when compared to ABVD (8%), the majority being neutropenic fever episodes. There was no treatment related mortality. The 3 year estimated EFS was 93.1% (Std.error=0.04) for the EURONET treated group whereas it was 71.9% (Std.error=0.044) for the ABVD group (Figure 2). Conclusions: This large single centre retrospective study of CHL in AYA patients shows better EFS and lesser requirement of RT in the EURONET treated group, at the cost of increased acute hematological toxicity. Though an age-matched direct comparison between the treatment groups was not feasible, this study suggests that chemotherapy intensification in the AYA group is possible and may potentially improve EFS while reducing the need for Radiotherapy. Disclosures Radhakrishnan: Pfizer, India: Honoraria, Speakers Bureau; Roche, India: Research Funding; Bristol Myers Squibb, India: Research Funding; Astra Zeneca, India: Honoraria, Speakers Bureau; Novartis, India: Honoraria, Speakers Bureau; NATCO pharmaceuticals: Research Funding; Emcure pharmaceuticals: Research Funding, Speakers Bureau; Dr. Reddys Laboratories: Speakers Bureau; Aurigene: Honoraria; Cipla: Honoraria, Research Funding, Speakers Bureau; Intas: Research Funding, Speakers Bureau. Chandy:NATCO Pharmaceuticals: Research Funding; Intas Pharmaceuticals: Research Funding. Nair:Intas Pharmaceuticals: Research Funding, Speakers Bureau; Cipla: Speakers Bureau; Dr Reddys Laboratories: Honoraria, Research Funding, Speakers Bureau.

HL-287: An Unusual Presentation of Discordant Classical Hodgkin and Non-Hodgkin Lymphoma in a Young Adult

Introduction Discordant lymphoma is the condition in which two subtypes of lymphoma occur synchronously in different anatomical sites. The objective is to highlight this exceptionally rare combination in order to prevent inaccurate diagnosis. Case Presentation A 20-year-old female presented with typical signs of diffuse supraclavicular and mediastinal lymph node enlargement. Based on the characteristic histological appearance of lymph nodes, she was diagnosed with classical mixed cellularity Hodgkin Lymphoma. Treatment was initiated with ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) chemotherapy. Following four cycles of therapy, the patient underwent a PET scan that revealed partial remission with persistence of mediastinal lymph nodes. Two additional cycles of ABVD were initiated, followed by a repeat PET scan that revealed new anterior and mediastinal lymph nodes with a necrotic center. Radiotherapy was done with a dose of 36 Gy in 20 fractions. Three months later following therapy, the patient underwent a PET scan that showed new onset sub-diaphragmatic lymph nodes with necrotic centers, although it showed a major decrease in the mediastinal lymph nodes previously described. A biopsy was performed on the new appearing nodes and was in favour of diffuse large B cell lymphoma, most likely of non-germinal center cell of origin, and was expressing CD30. Following this discovery, additional cycles of R-DHAP (rituximab, dexamethasone, high-dose cytarabine, and cisplatin) were administered, resulting in a significant decrease in sub-diaphragmatic lymph nodes. Conclusion Even if strict guidelines are followed, we must remain aware that several types of lymphoma can coexist simultaneously, and discordant lymphoma should be considered, especially when new lymph nodes appear despite adequate therapy, and a biopsy is always recommended. Identifying this rare entity can offer a survival benefit.

Clinical profile and outcome of classical Hodgkin lymphoma treated with a risk-adapted approach in a tertiary cancer center in India.

Classical Hodgkin lymphoma (cHL) has excellent survival rates, but late effects are an issue and dictate modern approaches. We analyzed the clinical profile and outcome of cHL treated on a risk-adapted approach aimed at reducing late effects while improving historical outcomes at our center. Children (≤15 years) consecutively treated for cHL from January 2013 through December 2016 were retrospectively analyzed. 18 FDG-PET-CT-based staging and response assessment was done after two cycles for early response (ERA) and end of chemotherapy (late-response assessment [LRA]) if not in complete response (CR; Deauville<4) at ERA. Stages IA/IB/IIA were low risk (LR) and received two cycles of ABVD (adriamycin/bleomycin/vinblastine/dacarbazine). Stages IAX/IBX/IIAX/IIB/IIIA were intermediate risk (IR), and stages IIBE/IIBX/IIIAE/IIIAX/IIIB/IVA/IVB were high risk (HR). Both received two cycles of OEPA (oncocristine/etoposide/prednisolone/adriamycin). Those in ERA-CR received two cycles of ABVD if LR, and two and four cycles of COPDac (cyclophosphamide/oncocristine/prednisolone/dacarbazine), respectively, for IR and HR. Involved-field radiotherapy (IFRT) was given to bulky sites and ERA<CR. Those at LRA<CR (Deauville<3) or progression at any stage received salvage regimens. In the study period, 126 patients were identified who received the above protocol. There were 12 LR, and 114 advanced staged Hodgkin lymphoma (AHL) (18, IR; 96, HR) of which 91 (79.8%) had bulky sites. Eight (66.6%) LR and 93 (83%) AHL patients achieved ERA-CRs. IFRT was given to 4 (33.3%) LR patients with ERA<CR, and 92 (80.7%) of AHL (91 bulky sites; 1 ERA<CR). At a median follow-up of 31 months (range, 17-62), three-year event-free survival (EFS) and overall survival (OS) were both 100% for LR, and 94.4% (95% CI, 66.0%-99.2%) for IR, whereas for HR it was 90.3% (95% CI, 82.2%-94.8%) and 92.6% (95% CI, 85.2%-96.4%), respectively. Children with HL have favorable outcomes with manageable toxicities when treated on a risk-stratified and adapted approach. A high proportion of AHL have bulky disease necessitating IFRT, a concern that will have to be factored in future strategies.

Therapeutic recommendations for early stage Hodgkin lymphomas.

Combined modality treatment has been the standard option for the treatment of early stage Hodgkin lymphoma for several decades. Because of the high success rate and the risk of late toxicities, recent clinical trials have focused on reducing the treatment burden. Field and dose of radiotherapy, and number of cycles of chemotherapy have been successfully reduced, particularly for favourable early stage patients. However, the impact of these treatment reductions on the rate of secondary malignancies remains still unclear. Positron emission tomography-computed tomography (PET-CT) scanning has emerged as a very important tool for disease staging and end of treatment assessment. Interestingly, a PET performed after 2 cycles of ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) has been correlated with final outcome and was recently evaluated in a randomized clinical trial to evaluate individualized therapy based on PET response after 2 or 3 cycles of ABVD. These trials aimed to identify good prognosis (early PET-negative) patients who could be spared radiotherapy, but also patients with a bad prognosis (early PET-positive) who need more intensive treatment. More recently, new drugs, such as brentuximab vedotin and checkpoint inhibitors, have shown efficacy in relapsed/refractory patients and are currently under evaluation in early stage patients.

Involved-site radiation therapy by volumetric modulated arc therapy versus 3D- conformal radiotherapy for treatment of stages I and II supra-diaphragmatic Hodgkin’s lymphoma

Purpose: Based on the observation that recurrences of Hodgkin's lymphoma (HL) typically occur in sites of initial nodal involvement the need to concise radiotherapy to only involved nodes that was termed as involved nodal radiotherapy (INRT) or of involved site lymph nodes, involved-site radiation therapy (ISRT) is starting to be widely accepted to use in early stage HL. We aimed in our study to compare between volumetric modulated arc therapy (VMAT) and 3D-conformal radiotherapy (3D-CRT) in radiation of early stage supra-diaphragmatic HL. Methods: The clinical and dosimetric data of 34 patients affected with stages I and II supra-diaphragmatic HL, treated between January 2011 and September 2015 with combined modalities therapy in a single institution were analyzed. Patients received 2-8 cycles of combination chemotherapy ABVD (Adriamycin, Bleomycin, Vinblastine & Dacarbazine) on days 1 and 15 repeated every 28 days. The clinical target volume (CTV) was contoured based on the pre-chemotherapy CT and PET-CT scans. Modification of the CTV was done according to post-chemotherapy anatomical changes. The radiation dose given was 30 Gy/15 fractions. Results: After a median follow up period of 30 months, the progression free survival (PFS) and overall survival (OS) in both groups were 100%. Oropharengeal mucositis was the commonest toxicity in both groups. There was no statistically significant deference between the acute radiation toxicities in both groups. The D mean valuefor lung was higher in 3D-CRT than VMAT (12.0 ± 6.1 Gy vs. 9.9 Gy ± 8.6 Gy). For the breasts volume, the V 5Gy was slightly higher for 3D-CRT compared with VMAT at, 7.6% and 6.5% respectively. For the heart, V 5Gy and V 10Gy valueswere higher for the RA than for 3D-CRT accounting for (51.9 ± 28.9%) and (41.0 ± 24.6%) versus (40.0 ± 25.9% and 30.7 ± 22.5%) respectively. Thyroid gland mean dose was lower for VMAT (21.8 ± 7.7 Gy) than for 3D-CRT (26.8 Gy ± 4.1 Gy) but did not reach statistically significant value ( P = 0.06). Conclusion: Involved-site VMAT technique is safe and effective in term of providing excellent local control and survival following ABVD-based chemotherapy.

Feasibility of Interim PET-Adapted Therapy in HIV-Positive Patients with Advanced Hodgkin Lymphoma (HL): Sub-Analysis of SWOG S0816 Phase 2 Trial

Background: The risk of HL is 10-fold higher in HIV-infected individuals than in the background population. Patients with HIV-HL typically present with advanced stage disease and frequent extranodal sites of involvement, accounting for higher risk scores than HIV-negative counterparts. Despite that, the prognosis of HIV-HL in the HAART era has been favorable. Standard ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) results in complete response rates (74%) and five-year overall survival (80%) similar to those in non-HIV-HL. Thus, as in HIV-negative HL, exploration of response-adapted therapy in HIV-HL is well-justified. PET imaging after 2 cycles of chemotherapy was found to be a strong predictor of treatment outcome in patients with non-HIV-HL. Here, for the first time, we report on the outcomes of HIV-positive patients enrolled on S0816, a multicenter Phase 2 trial of response-adapted therapy of stage III-IV HL using interim FDG-PET imaging.Methods: HIV-positive patients aged 18-60 with previously untreated stage III-IV classical HL were eligible. Patients with multi-drug resistant HIV or concurrent AIDS-defining conditions were excluded. All patients received 2 cycles of ABVD followed by an interim PET, reviewed centrally. Patients with negative PET (Deauville≤3) subsequently received 4 additional cycles of ABVD, while PET-positive patients received 6 cycles of BEACOPP standard regimen (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine and prednisone).Results: 12 patients with HIV-HL received study treatment. Median age was 44.6 years (range, 25 to 50 years), 83.3% were male. 11/12 (91.6%) patients presented with bulky lymphadenopathy (≥10 cm) and 50% had poor risk international prognostic score (IPS≥4). 6/12 (50%) patients manifested B-symptoms and 33.3% had bone marrow involvement by HL. Where information was available, most patients (7/9, 77.8%) received concurrent HAART during chemotherapy. Median CD4 count prior to registration was 165/µL (range, 22-400/µL), and <100/µL in 5/12 pts (41.7%).All HIV-HL patients successfully completed 2 initial cycles of ABVD. Gr 4 neutropenia and gr 3 febrile neutropenia were common during this treatment (66% and 25%, respectively). 10/12 (83.3%) patients achieved PET-negative status and 2 remained PET-positive with Deauville scores of 4 and 5. All PET-negative patients continued therapy with ABVD. Of those, nine completed the 4 cycles of treatment and one discontinued early for progressive disease 4 months after registration on study. Of the PET-positive patients, one elected to receive ABVD therapy off the study protocol, while the other completed 6 cycles of BEACOPP; both achieved a partial response. Thus, following ABVD therapy, 82% of patients achieved complete response and 18% - partial response. With median follow-up of 31 months (range, 5.4-38.1 months) all study patients are alive. Two patients developed progressive disease, with the estimated progression-free survival of 83% at 2 years (95% CI, 46.1 to 95.3%). Most grade 3-4 adverse events with continued therapy were neutropenia (72.7%) and febrile neutropenia (27.2%), while other toxicities were uncommon (see Table). All 12 patients experienced at least one grade 3-4 toxicity during study treatment. 3 patients (25%) required dose reductions due to febrile neutropenia (N=2) and neuropathy (N=1).Conclusions. ABVD is highly effective in patients with advanced stage poor-risk HIV-HL and induces PET-negative responses at a similar rate without undue added toxicity as compared to non-HIV patients in a prospective trial setting. As response-adapted therapy evolves to be a standard approach for HIV-negative patients with advanced stage HL, the results of S0816 study presented here support a similar investigative approach in patients with HIV-HL, with the goal of reducing long-term toxicity. The role of intensified chemotherapy regimens in patients with HIV-HL who do not achieve PET-negative status needs further study. Table 1ToxicityGrade 3, N (%)Grade 4, N (%)Anemia2 (18.2)2 (18.2)Febrile neutropenia3 (27.2)-Lymphopenia1 (9.1)2 (18.2)Neutropenia2 (18.2)6 (54.5)Thrombocytopenia1 (9.1)-Infection2 (18.2)-Anorexia1 (9.1)-Dizziness1 (9.1)-Fatigue1 (9.1)-Hypophosphatemia1 (9.1)-Musculoskeletal pain1 (9.1)-Thrombosis1 (9.1)- DisclosuresSmith:Pharmacyclics: Consultancy; Celgene: Consultancy.

Sustained remission after ABVD treatment for interdigitating dendritic cell sarcoma.

Sustained remission after ABVD treatment for interdigitating dendritic cell sarcoma.

FDG-PET/CT in Early Assessment of Response to Therapy in Pediatric Hodgkin Lymphoma

Purpose of the study: was to estimate the value of early assessment of response in pediatric Hodgkin lymphoma (PHL) patients using FDG-PET/CT. Methods: prospective analysis of 195 patients presented in Children’s Cancer Hospital, Egypt (CCHE) with pathologically proven untreated PHL, they underwent18 F-fluorodeoxyglucose positron emission tomography (F-18 FDG PET/CT) early after 2 cycles of chemotherapy (PET 2).This chemotherapy regimen consists of concurrent treatment with Adriamycin, Bleomycin ,Vinblastine & Dacarbazine (ABVD). Analysis of PET 2 was done according to the Deauville score (5-point score) with cut-off 3-4 between Minimal Residual Uptake (MRU) and positive result. Results: Follow-up was done for mean period of 2.9 years (range, 0.6 to 5.2 years).Visual assessment of PET 2 was found to be significantly correlated with Overall Survival (OS) and Progression Free Survival (PFS) in advanced stages PHL (intermediate and high risk patients); the estimate for OS and PFS was 83.3% and 68.8 respectively in the PET-positive (PET +ve) group compared with 97.3% and 92.6|% respectively in the PET-negative (PET – ve) group (p-value <0.0001 and 0.0001).Conclusion: Early assessment of FDGPET/CT after 2 cycles of ABVD in PHL shows potential value in prediction of OS and PFS in advanced stages (intermediate and high risk patients).

Treatment of early-stage Hodgkin's lymphoma outcome ( Kuwait experience)

Introduction Treatment of early-stage classical Hodgkin’s lymphoma (HL) is changing targeting remission with reduced intensity. Aim of the work This study presents a review of treatment of earlystage I and II HL patients treated with adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) with or without radiotherapy. Materials and methods Data were analyzed retrospectively from files of patients treated at the Kuwait cancer center from 2002 to 2010. The study included 105 patients divided as follows: group A, which included 34 patients treated by four cycles of ABVD, and group B, which included 71 patients treated by six cycles of ABVD. Results Unfavorable risk cases were 47 versus 77.4% in group A versus B. Radiotherapy was added to ABVD in 57.1% of patients; 35.3% of these patients were from group B. No significant difference in remission or relapse was noted between groups A and B ( P =0.04). The 5-year overall survival (OS) for patients was 86%, with no difference between the two groups. Patients with B symptoms had significantly lower 5-year OS (73 vs. 92%; P =0.02). Although the presence of bulky disease and erythrocyte sedimentation rate 50 mm/h or more are associated with lower OS, the difference was not significant ( P >0.05). Combined therapy yielded better 5-year OS (90.3%) than chemotherapy alone (80.4%), without significance ( P =0.29). No cardiopulmonary toxicities or second malignancies were noted but hypothyroidism was evident after neck radiation. This indicates the good outcome of early-stage HL in general. Some prognostic factors could address treatment policy in terms of the presence of B symptoms, bulky disease, and high erythrocyte sedimentation rate. Conclusion Modification of therapy on the basis of novel prognostic factors may be of prospective interest.

Hodgkin's lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

D. A. Eichenauer1, A. Engert1, M. Andre2, M. Federico3, T. Illidge4, M. Hutchings5, & M. Ladetto6 on behalf of the ESMO Guidelines Working Group* First Department of Internal Medicine, University Hospital Cologne and German Hodgkin Study Group (GHSG), Cologne, Germany; CHU Dinant-Godinne, UCL Namur, Yvoir, Belgium; Department of Oncology, Hematology and Respiratory Diseases, University of Modena and Reggio Emilia, Modena, Italy; Institute of Cancer Sciences, University of Manchester, Manchester, UK; Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; Divisione di Ematologia, Azienda Ospedaliera Santi Antonio e Biagio e Cesare Arrigo, Alessandria, Italy

Interim PET in lymphoma: a step towards standardization

In this issue, Barrington et al. propose well-defined criteriafor interim PET/CT reporting in lymphoma [1]. Thesecriteria, based on a five-point scale, introduce two mainconcepts which are highly relevant for interim PETanalysis: (1) the intensity of the residual uptake frequentlyobserved at interim is graded relative to various levels ofreference background (RB)—mediastinal blood pool(MBP) and liver—and (2) this grading process is indepen-dent of the size of the residual tumour. Furthermore, theauthors reported that this five-point scale assessed on asample of 50 patients with advanced stage Hodgkin’slymphoma (HL) by 4 pairs of experts from 4 Europeancentres: (1) seems a reproducible tool for guiding thera-peutic strategy after 2 cycles of ABVD (Adriamycin,bleomycin, vinblastine, dacarbazine) when liver is chosenas an RB and (2) is robust enough to be used in multicentretrials for interim PET reporting.The authors have decided to use this scale in theResponse Adapted Treatment in Hodgkin Lymphoma(RATHL) trial, an interim PET-driven therapeutic strategyin patients with advanced stage HL. Although manytrials are ongoing worldwide in HL and non-Hodgkin’slymphoma (NHL) to test whether the results of an interimPET performed after one to four cycles of chemotherapycan tailor a response-adapted therapy, standardized interimPET criteria are still missing. Interim PET requires indeedspecific criteria which should be different from thosedefined for end treatment by the International Harmoniza-tion Project (IHP) in Lymphoma [2]. In the context of drugdevelopment and survival improvement observed inlymphoma, the rationale of interim PET is to define ana posteriori prognostic index reflecting tumour chemo-sensitivity during first-line therapy, allowing earlychanges of therapy (escalation or de-escalation) adaptedto specific situations. In many trials the strategy can bemodified according to the results of two interim PETexams performed at different times during inductiontreatment. As a matter of fact, depending on thecharacteristics of tumour growth and histological typethe evolution of PET under treatment is different. Indiffuse large B-cell lymphoma (DLBCL) neoplastic cellsconstitute more than 90% of the total cell population.The metabolic activity during therapy decreases in acontinuous mode, with cell killing. Interim PET after oneor two cycles of chemotherapy evaluates the response ofthe cells with the highest mitotic index, thereby providingan early evaluation of chemosensitivity and identifyingresponders and non-responders [3, 4]. On the other hand,after three or four cycles of therapy, FDG uptake is moredependent on the tumour regrowth [5]. In HL, the Reed-Sternberg (RS) cells account for less than 1% of the tumour.Bystander, lymphomononuclear cells work, throughcytokines, as an amplifier of the PET detection power. Thesecells are switched off very early (one to two cycles) bychemotherapy [6]. Therefore, the amount of residual activityat interim varies with the kinetics of tumoral destruction, thehistology of lymphoma, the tumoral microenvironment, thetreatment and the time point (two cycles or more) at whichPET is performed. These variations are better described by aquantitative analysis by reference to the baseline PET thanby using a visual dichotomous analysis (positive or negative)which results in a loss of information [3, 5]. In this regard thefive-point scale proposed by Barrington et al. is goingtowards the right direction by giving the possibility to grade

Posttransplant Lymphoproliferative Disorder Followed by Hodgkins Disease in a Renal Transplant Recipient

Posttransplant lymphoproliferative disorder (PTLD) is an uncommon but potentially fatal complication affecting 1% to 3% of renal transplant recipients. The term “PTLD” encompasses a spectrum of disorders ranging from polyclonal lymphoproliferation to monoclonal lymphomas, which are often Epstein-Barr virus (EBV) positive, aggressive B-cell non-Hodgkins lymphomas but Hodgkins lymphomas can also arise in this setting. We report a patient who developed mixed cellularity Hodgkins lymphoma 1 year after treatment for diffuse large B cell lymphoma arising post renal transplantation. A 34-year-old gentleman received a cadaveric renal transplant in August 1996 for end stage renal failure of unknown cause. Posttransplant immune suppression was with ciclosporin and prednisolone. He presented in September 2002 with a lump in the left axilla, which on further investigations was shown to be EBV positive high grade diffuse large B-cell lymphoma (stage IB). He went into remission with withdrawal of immune suppression and six courses of R-CHOP chemotherapy (rituximab, cyclophosphamide, daunorubicin, vincristine, prednisolone) with subsequent radiotherapy to a residual lymph node mass in the left axilla. Immune suppression with ciclosporin and prednisolone was reinstituted in view of deteriorating renal function. In July 2004, he presented with sweats and progressively enlarging lymph nodes in the right axilla. A biopsy confirmed mixed cellularity Hodgkins disease. Some of the RS cells showed positivity for EBV. He was staged as having IB disease. He was treated with two cycles of ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) in December 2004 and this was followed by radiotherapy to the right axilla in January 2005. He remains well and in complete remission 39 months posttreatment and has never suffered any episodes of graft rejection, though we have been unable to reduce the dose of prednisolone to less than 5 mg because of deterioration renal function. Hodgkin's lymphoma arising as a second PTLD, after treatment for an initial PTLD, is a very rare occurrence. There are only four such cases reported in literature, all occurring in the pediatric solid organ transplant setting. Initial PTLD was of the polymorphic subtype in three and “Hodgkins-like” in the fourth reported case (Table 1).TABLE 1: Clinical information of posttransplant Hodgkins lymphoma subsequent to other subtypes of PTLDThe treatment of Hodgkins disease after PTLD raises problems in terms of use of anthracylines and cardiotoxicity. In the four cases previously reported (Table 1), the PTLD had responded to withdrawal of immunosuppression or antiviral therapy and α interferon. Hodgkins disease was subsequently treated with cyclophosphamide, vincristine, prednisone and procarbazine/adriamycin, bleomycin and vinblastine in two cases, mechlorethamine, vincristine, prednisone, procarbazine in one case and unspecified chemotherapy in one case. One patient with recurrent Hodgkins disease had six cycles of ABVD. During relapse he had an unspecified number of cycles of ABVD after which adriamycin was substituted and bleomycin was stopped in view of cardiac and lung toxicity (5). De novo limited stage Hodgkins disease is normally treated with 4 to 6 cycles of combination therapy. Cardiac toxicity resulting from cumulative anthracycline therapy is generally seen at doses above 450 to 500 mg/m2. The cumulative anthracycline dosage our patient received with CHOP and ABVD chemotherapy was 400 mg/m2. In view of limited stage disease and concern about anthracycline induced cardiomyopathy, he discontinued chemotherapy after two cycles of ABVD, after which he received radiotherapy. Recommendations for managing similar patients cannot be made based on a single case. There is no evidence to suggest that chemotherapy for diffuse large B cell lymphoma increases the risk of subsequent Hodgkins disease. All the cases reported so far have responded to conventional chemotherapy though the long-term outcome in these patients is not known. Common clonality is suggested by the temporal relation between the non-Hodgkins lymphoma and Hodgkins disease and also because both tumors were EBV positive, though conclusive evidence for this is not available. Anand Lokare Sridhar Chaganti Department of Haematology University Hospital Birmingham NHS Foundation Trust Birmingham, United Kingdom Graham Lipkin Department of Nephrology University Hospital Birmingham NHS Foundation Trust Birmingham, United Kingdom Claudia Roberts Department of Cellular Pathology University Hospital Birmingham NHS Foundation Trust Birmingham, United Kingdom Prem Mahendra Department of Haematology University Hospital Birmingham NHS Foundation Trust Birmingham, United Kingdom

Early Interim Negative FDG-PET/CT Is a High Predictive Factor for Progression-Free Survival in Hodgkin Lymphoma.

The treatment of patients with Hodgkin lymphoma (HL) is currently based on pretreatment risk stratification aimed at reducing late therapy-related toxicity. Functional Gallium67 scintigraphy was previously used for an interim assessment of response to therapy. Recently, an interim FDG-PET was suggested as a prognostic parameter for a failure-free survival. Reported here is the significance of an interim PET when integrated into a therapeutic protocol and used for an interim risk assessment. A cohort of 89 patients with Hodgkin lymphoma treated in a single medical center since 2001 was evaluated. Three patients had stage I disease, 48 - stage II, 15 - stage III and 23 - had stage IV. Assessment of the patients using the International Prognostic Score (IPS) showed that 20% had early disease with no score evaluable, in 18% the score was 0–2 and 62% of patients had a score of 3–6. Twenty eight patients were treated with 6 cycles of ABVD (Adriamycin, Bleomycin, Vinblastine, Dacarbazine) and 61 patients received BEACOPP combinations (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) for 6 cycles. Baseline PET/CT was performed in 87 patients while following 1st, 2nd or 3rd cycle of chemotherapy this test was repeated in 15, 70 and 4 patients, respectively. The 3-year failure-free survival (FFS) and the overall survival (OS) for patients with an interim negative study compared to those with an interim positive study were 95% versus 79% and 98% versus 89%, respectively. A subgroup of 11 patients who received escalated therapy following a positive interim PET had a 73% FFS. Three of these patients had primary progressive disease despite interim escalation of therapy. The 3-year negative predictive value of PET/CT was independent of patient risk group or chemotherapy used. Assessing the positive predictive value is difficult owing to the relatively small number of patients (19) as well as the dilemma of interpreting outcome therapy that was intensified based on the interim positive scintigraphy. Never-the-less, the data indicate that at least 27% of patients with a positive interim PET/CT will not be disease free at 3 years. The hazard ratio for a positive interim PET study is 6.2 CI (1.5–26), p=0.012. In conclusion, an interim negative PET/CT is highly predictive of prolonged FFS and OS. Prospective studies are needed to determine whether such an interim negative scan can be used to further reduce the dose intensity. An interim positive scan portends a poorer prognosis although the precise degree of predictability cannot be assessed from this study where therapy was escalated as a result of such scintigraphic findings.Interim PET3-yr FFS3-yr OSMedian follow up - monthsn%Negative study: Group A (n=70)67/7095.3%98.1%29 (5–55)Positive study: Group B: Residual uptake (n=19)14/1979.0%89.2%36 (7–66)Escalation of therapy post positive study: Group C: (n=11)8/1172.7%81.8%37Log rank test:Groups A vs B: 0.004Groups A vs B: 0.05Groups A vs C: 0.007Groups A vs C: 0.008

A selective history of the therapy of Hodgkin's disease.

A selective history of the therapy of Hodgkin's disease.

Treatment of Early Clinically Staged Hodgki n's Disease with a Combination of ABVD Chemotherapy plus Limited Field Radiotherapy

The current management of early stage Hodgki n's disease (HD) is usually based on clinical staging, combined modality therapy and the use of less toxic chemotherapy regimens. This approach entails high cure rates, while ensures less long term toxicity with avoidance of laparotomy. The aim of this study was to assess the efficacy of a brief course of Adriamycin, Bleomycin, Vinblastine, Dacarbazine (ABVD) chemotherapy followed by limited field radiotherapy (RT) in favorable clinical stage (CS) I and IIA HD. Forty patients, aged 17–68 (median 34) years, with favorable CS I and IIA HD, without bulky mediastinal disease, have been treated with 4–6 (median 4) cycles of ABVD plus limited field RT. Twenty seven (67%) patients received 4 cycles of chemotherapy, while 13 received 5–6 cycles. Thirty five (87%) patients received limited field RT with dose 24–36 Gy and five (13%) received extended field with 36–46 Gy. All patients responded completely to chemotherapy. One patient experienced a relapse two months after the end of therapy. All patients are alive; 39 in continuous complete remission. With a median follow-up period of 44 months (range 18–101) the actuarial overall and progress free survival was 100 and 97% at 5 years. We did not observe any case of secondary leukemia or solid tumor. Pulmonary toxicity was mild in cases of mediastinal irradiation. Considering the short follow-up time and the small number of patients, the combination of a brief course of ABVD plus regional RT is a very efficacious treatment of favorable CS I and IIA HD with mild toxicity. However, long term survival data are needed, which could give confident answers regarding the risk of late therapy related complications, particularly second malignancies.