Adriamycin, Bleomycin, Vinblastine And Dacarbazine Research Articles

History of ABVD alters the number of oocytes vitrified after in vitro maturation in fertility preservation candidates.

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. 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. 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). In light of these results, FP should be discussed before ABVD.

A Case of Disseminated Extranodal Interdigitating Dendritic Cell Sarcoma Arising from Parotid Gland

Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare tumor derived from professional antigen presenting cell and primarily found in lymph nodes, with rarer case report about extranodal presentation of IDCS. A 71-yr-old man was admitted with progressively enlarging and painless mass in the right parotid area for 2 months. Computed tomography of the neck and chest revealed enhancing mass in right parotid gland, multiple lymphadenopathies around neck and mediastinum, and an osteolytic metastasis at thoracic spine. Morphological and immunohistochemical analysis of an excisional biopsy specimen from parotid mass were consistent with a diagnosis of IDCS. Palliative chemotherapy with 6 cycles of CHOP (cyclophosphamide, adriamycin, vincristine, and prednisolone) regimen and 2 cycles of ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine) regimen plus radiotherapy on parotid mass failed in tumor reduction. We describe a rare case of disseminated extranodal IDCS arising from parotid gland.

Radiation Pneumonitis Risk after Bleomycin Toxicity in Hodgkin Lymphoma Patients

Introduction:Combined modality treatment with Adriamycin, Bleomycin, Vinblastine and Dacarbazine (ABVD) chemotherapy followed by consolidative radiation to start within 3-4 weeks is the current accepted approach in the treatment of patients with early stage Hodgkin lymphoma (HL). Bleomycin pulmonary toxicity (BPT) is a well-known complication of treatment in HL patients. We undertook this study to investigate the risk of radiation pneumonitis (RP) in the setting of BPT and to determine the need for delay or omission of radiation in these patients.Methods:We reviewed the records of all HL patients treated with ABVD followed by radiation therapy (RT) to the chest between January 2009 and December 2014. We defined bleomycin toxicity as: the occurrence of clinical respiratory symptoms leading to discontinuation of bleomycin and/or bilateral opacities noted on computed tomography (CT) imaging and/or drop in diffusing capacity of the lung for carbon monoxide (DLCO) by 25%, in the absence of infection. We identified 129 patients, 100 of which received consolidation RT as part of combined modality and are the subject of this report, 29 patients were excluded because they developed relapse before getting RT. We compared patients with and without bleomycin toxicity for the following outcomes:•Frequency of RP using the Pearson chi-square test.•Interval between BPT and Radiation using Mann-Whitney U test (MWT)•Interval between end of chemotherapy and radiation using MWT.We used univariate Cox regression analysis to assess the risk of RP by looking at the time-interval in weeks from end of bleomycin to start of RT.Results:Median follow up was 23 months (6 - 69), Median age was 31 years (18-77), and 60% were females. Per our criteria, 28 patients developed BPT (25.5%). All patients received intensity modulated radiation therapy, radiation dose median was 30.60 Gy (20-42Gy). Mean lung dose (MLD) was a median of 9.4 Gy (2.6- 13.9 Gy). The median interval between chemotherapy and RT was 3 weeks (1- 8 weeks). Median interval from stopping bleomycin, either as a precaution or because of toxicity, to the start of RT was 5 weeks (1-20 weeks). Interval between documented bleomycin toxicity to start of radiation was a median of 8.5 weeks (2-20 weeks).We had 10 cases of RP (10%), 5 of which were ≥ Grade 2. There was no significant difference in RP risk in patients with or without BPT; 10.7% (3/28) versus 9.6% (7/72) respectively, P= 0.82.Patients with BPT versus those without BPT had no significant difference in baseline characteristics. The interval time from chemotherapy to radiation was a median of 3 weeks in both groups with or without BPT showing no difference; P= 0.83. However, Patients with BPT had a significantly longer interval from last bleomycin cycle to start of radiation compared to those without BPT (median 8.5 vs. 5 weeks, p =0.014).The intervals from chemotherapy to radiation treatment and from bleomycin to radiation treatment showed no significant correlation with RP on univariate Cox regression analysis (P= 0.41 and P= 0.12, respectively). This was maintained when adjusted for the number of bleomycin cycles.Treatment of BPTOf the 28 patients, 17 were managed by stopping bleomycin and observation only; 10 patients required a 2 week course of steroids. One patient went into severe respiratory compromise, was started on continuous oxygen and eventually recovered 48 hours later and went on to receive RT beginning 2 weeks after completing his steroid treatment. This patient did not have pulmonary complications after RT.All 28 BPT patients eventually completed their planned course of radiation. At last follow up, all 28 patients were alive and free of respiratory symptoms.Conclusion:In our cohort of Hodgkin lymphoma patients, those patients with bleomycin toxicity who received standard RT had no excess risk of subsequent RP. Moreover, patients were able to receive complete courses of RT to intended conventional radiation doses. Our findings suggest that RT does not need to be delayed following chemotherapy, except to allow for the completion of steroids or clinical recovery from BPT.Table 1BPT_clinicalBPT _imagingBPT_DLCO≥25%Clinical+(CTorDLCO≥25%)BPT per criteriaAll patients n=1002517101328RPNo n=90221591225Yes n=1032113 DisclosuresNo relevant conflicts of interest to declare.

Review and follow-up of patients using a regional sperm cryopreservation service: ensuring that resources are targeted to those patients most in need.

Are all patients undergoing chemotherapy for long-term sperm banking at risk of permanent sterility? Male fertility is generally lower in men with cancer and all patient groups are at risk of azoospermia. Careful management is required to ensure that samples are not stored for excessively long periods should they not be required. A retrospective analysis of 1688 patient records and prospective recall of patients for semen testing were performed. Pre-therapy fertility was compared with a group of pre-vasectomy patients as a comparator. Those who fail to bank spermatozoa, rates of disposal of samples and the utilization in assisted reproduction were also examined. Sperm quality was poorest in testicular cancer (TC) patients followed by those with Hodgkin's lymphoma (HL) prior to treatment. Post-therapy data were available in 376 patients (42%). Sperm number was lowest (and azoospermia highest at 77%) in patients with HL treated with regimens other than adriamycin, bleomycin, vinblastine and dacarbazine (ABVD). Non-HL NHL and leukaemic patients had similarly high rates of azoospermia at 46 and 55%. HL patients treated with ABVD (11%) and TC patients (9.7%) had the lowest rates of azoospermia. Azoospermia was seen in every treatment group except for TC patients receiving carboplatin. Only 45 patients used their samples in ART (4.5%) in 10 years. Little is known about the fertility status of the patients not coming forward for follow-up testing, those conceiving naturally, those with no intention of conceiving and some which may have psychological reasons for not attending. In conclusion, virtually all patients undergoing chemotherapy are potentially at risk of temporary or permanent infertility. However, as uptake and utilization of stored material remain low, sperm banks should be carefully managed to ensure that resources are targeted to the patients most in need.

Unusual primary osseous Hodgkin's lymphoma: A case report.

Hodgkin’s lymphoma (HL) is one of the few adult malignancies that most frequently presents with a progressive, painless enlargement of the peripheral lymph nodes. A primary osseous presentation of HL, without lymph node involvement, is extremely rare. The present study describes a case of primary multifocal osseous HL in a 22-year-old female. The patient presented with pain in the lumbar-sacral-pelvic area and a prolonged fever. Pathological examination led to a diagnosis of primary multifocal osseous lymphoma, and the patient was subsequently prescribed a course of Adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy. Following this, the patient recovered with no pain or fever, and computed tomography identified no further progression. The clinical, radiological and histological features of HL are similar to those of other medical conditions, such as tuberculosis and eosinophilic granuloma. Furthermore, in rare cases, HL may even occur in combination with multiple myeloma. This makes it difficult to diagnose the condition, which often leads to a delay in treatment. Clinicians should not ignore HL when it manifests in the unusual primary osseous form.

Granulocyte colony-stimulating factor as secondary prophylaxis of febrile neutropenia in the management of advanced-stage Hodgkin lymphoma treated with adriamycin, bleomycin, vinblastine and dacarbazine chemotherapy: a decision analysis

Current practice guidelines are unclear regarding the role of secondary prophylaxis of febrile neutropenia in advanced-stage Hodgkin lymphoma despite several small retrospective studies that demonstrate the omission of growth factors to be a safe and economic practice. We used a decision-analytic model to compare secondary prophylaxis with granulocyte colony-stimulating factor (G-CSF) to no G-CSF with the onset of severe neutropenia for a hypothetical cohort of patients with advanced-stage Hodgkin lymphoma treated with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD). There was a net benefit of 0.017 years and 0.037 quality-adjusted life years for no G-CSF use in severe neutropenia. On microsimulation (10 000 trials), 96% of the simulations showed that the no G-CSF strategy is preferred to the use of G-CSF. This finding was robust across a wide range of sensitivity analyses. Our analysis suggests that G-CSF not be used as secondary prophylaxis of febrile neutropenia in advanced-stage Hodgkin lymphoma.

Interim positron emission tomography and clinical outcome in patients with early stage Hodgkin lymphoma treated with combined modality therapy

The aim of the study was to investigate whether interim positron emission tomography (iPET) is prognostic in a cohort of patients with early stage Hodgkin lymphoma (HL) homogeneously treated with 3–4 cycles of ABVD (adriamycin, bleomycin, vinblastine and dacarbazine) followed by 30 Gy involved field radiotherapy. Eighty patients were selected (stage I–IIA HL, availability of iPET, minimum follow-up of 12 months), and after central review, 70 were judged negative (iPET−: 87.5%) and 10 positive (iPET+: 12.5%). The two groups were then analyzed for response, progression-free survival (PFS) and overall survival (OS). Only one out of 70 iPET− patients relapsed, with 69 in continuous complete remission (CCR). All 10 iPET + patients achieved a complete response and maintained persistent CCR at follow-up. The 3-year PFS and OS were, respectively, 97% and 98.4% for iPET− and 100% and 100% for iPET+ (p = 0.63). iPET positivity does not seem to be a significant prognostic factor, and change in therapeutic strategy on the basis of iPET does not appear currently advisable outside clinical trials.

Interim fluoro-2-deoxy-D-glucose–PET predicts response and progression-free survival in patients with Hodgkin lymphoma and HIV infection

Interim PET scans in HIV-negative patients with Hodgkin lymphoma has emerged as one of the most important prognostic tools. However, equivalent studies in HIV-positive patients are yet to be performed. We evaluated the prognostic value of interim [18F]-fluoro-2-deoxy-D-glucose-PET (18F-FDG PET) after two or three cycles of chemotherapy using adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) with concomitant HAART in HIV-positive patients with Hodgkin lymphoma. Patients with advanced HIV-Hodgkin lymphoma (HIV-HL) from six UK centres were included. Interim PET scans after two or three cycles of ABVD (PET-2 or PET-3) were carried out. Prognostic analysis correlated the 2-year progression-free survival (PFS) rate with the interim PET result. Twenty-three evaluable patients were assessed, 21 achieved a negative interim PET and 22 achieved complete remission by computerized tomography scan criteria after ABVD therapy. After a median follow-up of 27 months (range 12-50), disease progression was seen in one patient. Treatment failure was seen in one of the two interim PET-positive patients and none of the interim PET-negative patients. The 2-year PFS for interim PET-positive patients was 50%, and 100% for interim PET-negative patients (P = 0.0012). A negative interim 18F-FDG PET result is highly predictive of treatment success in HIV-HL patients.

Poor prognosis of Hodgkin variant of Richter transformation in chronic lymphocytic leukaemia treated with cladribine ‐ Response to Jamroziak et al

We appreciate the thoughtful comments of Jamroziak and colleagues regarding our study of Hodgkin lymphoma as Richter transformation (Hodgkin-RT) in patients with chronic lymphocytic leukaemia (CLL) (Bockorny et al, 2012). Mirroring our pooled analysis that showed a decreased survival in Hodgkin-RT patients previously treated with fludarabine (0.7 ± 0.2 years), their retrospective analysis demonstrated similarly unsatisfactory outcomes in Hodgkin-RT patients treated with cladribine-based regimens for CLL. Of note, they showed a survival of only 0.34 years (95% confidence interval 0–1.08) in a small cohort of Hodgkin-RT patients whose CLL had previously been treated with cladribine (n = 6). A plausible explanation for this dismal outcome is the marked and prolonged T-lymphocyte depletion caused by the purine nucleoside analogues (PNAs), which amplifies the intrinsic immunosuppression of CLL and possibly leads to reactivation of a latent Epstein-Barr virus infection (Cheson et al, 1999; Dasanu, 2008). In addition, Jamroziak et al hypothesized that the first-line chemotherapy commonly used to treat Hodgkin transformation in CLL might be suboptimal against the PNA-exposed clones. In our cohort, the most commonly employed regimens for Hodgkin-RT therapy were ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine) and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), with no statistical difference in overall survival between the two groups. As of today, the best therapeutic approach for Hodgkin-RT remains to be clarified (Tsimberidou et al, 2006). Rituximab with or without chemotherapy remains an attractive option for Hodgkin-RT cases with CD20+ Reed-Sternberg cells or marrow/ nodal histologies composed of a mix of Hodgkin lymphoma and CLL. In conclusion, the outcome of the Hodgkin variant of Richter syndrome in CLL, especially when previously exposed to PNAs, should not be viewed as favourable when compared to the classic RT (as diffuse large B-cell lymphoma). Selection of a more intense first-line chemotherapy regimen, with or without targeted antibody therapy may improve the general outcome. Studies aiming to clarify the molecular basis of Hodgkin-RT along with the discovery of innovative therapeutic approaches for this rare variant of RT are awaited. The authors have no competing interests.

Dose-Intensification in Early Unfavorable Hodgkin's Lymphoma: Final Analysis of the German Hodgkin Study Group HD14 Trial

In patients with early unfavorable Hodgkin's lymphoma (HL), combined modality treatment with four cycles of ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine) and 30 Gy involved-field radiotherapy (IFRT) results in long-term tumor control of approximately 80%. We aimed to improve these results using more intensive chemotherapy. Patients with newly diagnosed early unfavorable HL were randomly assigned to either four cycles of ABVD or an intensified treatment consisting of two cycles of escalated BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone) followed by two cycles of ABVD (2 + 2). Chemotherapy was followed by 30 Gy IFRT in both arms. The primary end point was freedom from treatment failure (FFTF); secondary end points included progression-free survival (PFS) and treatment-related toxicity. With a total of 1,528 qualified patients included, the 2 + 2 regimen demonstrated superior FFTF compared with four cycles of ABVD (P < .001; hazard ratio, 0.44; 95% CI, 0.30 to 0.66), with a difference of 7.2% at 5 years (95% CI, 3.8 to 10.5). The difference in 5-year PFS was 6.2% (95% CI, 3.0% to 9.5%). There was more acute toxicity associated with 2 + 2 than with ABVD, but there were no overall differences in treatment-related mortality or secondary malignancies. Intensified chemotherapy with two cycles of BEACOPP escalated followed by two cycles of ABVD followed by IFRT significantly improves tumor control in patients with early unfavorable HL.

Optimisation de l’« involved-node radiotherapy » par l’utilisation de la modulation d’intensité dans le lymphome hodgkinien localisé : expérience de l’institut Gustave-Roussy

Purpose To assess the clinical outcome of the involved-node radiotherapy concept with the use of intensity modulated radiotherapy (IMRT) in patients with localized supradiaphragmatic Hodgkin lymphoma. Patients and methods Patients with early-stage supradiaphragmatic Hodgkin lymphoma were treated with chemotherapy prior to irradiation. Radiation treatments were delivered using the involved-node radiotherapy (INRT) concept according to the EORTC guidelines. Intensity modulated radiotherapy was performed free-breathing. Results Forty-seven patients with Hodgkin lymphoma (44 patients with primary Hodgkin lymphoma and three patients with recurrent disease) entered the study from January 2003 to December 2010. The median age was 31 years (range 17 to 62). Thirty patients had stage I-IIA, 14 had stage I-IIB disease and three had relapse. Forty-two patients received three to six cycles of adriamycin, bleomycin, vinblastine and dacarbazine (ABVD). The median radiation dose to patients was 36 Gy (range: 20–40). Protection of various organs at risk was satisfactory. The median follow-up was 57.4 months (range: 5.4–94.3). For patients with primary Hodgkin lymphoma, the 5-year survival and 5-year progression-free survival rates were 96% (95% confidence interval: 80–99) and 92% (95% confidence interval: 78–97), respectively. None of the three patients with recurrent disease has relapsed. Recurrences occurred in three patients: one was in-field relapse and two were visceral recurrences. Grade 3 acute lung toxicity (transient pneumonitis) occurred in one case. Conclusion Our results suggest that patients with localized Hodgkin lymphoma can be safely and efficiently treated using the involved node irradiation concept and intensity modulated irradiation.

Incidence and Predictors of Bleomycin Pulmonary Toxicity in Hodgkin Lymphoma (HL) Patients Treated with Adriamycin, Bleomycin, Vinblastine and Dacarbazine (ABVD),

Abstract 3643 Background:Bleomycin pulmonary toxicity (BPT) is a well described complication of bleomycin-containing chemotherapy regimens, with a reported incidence of 0–46%. Prior data in Hodgkin Lymphoma (HL) have been heterogeneous with some series reporting inferior survival in patients (pts) with BPT. We reviewed the outcome of ABVD treated pts at our institution with the goals of determining the incidence and risk factors for BPT, as well as the effect of BPT on overall and progression-free survival (OS and PFS). Methods:We retrospectively reviewed 253 newly diagnosed pts with HL treated with ABVD at Princess Margaret Hospital from 1999–2009. Pts typically received 3 cycles of ABVD + IFRT for localized disease and 6–8 cycles for advanced stage or bulky disease. BPT was defined by the presence of symptoms (fever, cough, dyspnea), bilateral interstitial infiltrates on CT, and no evidence of infection. Predictors of BPT were identified in bivariate followed by multivariable logistic regression analysis. Kaplan-Meier estimates as well as Cox proportional hazards model were used to compare OS and PFS between groups. Results:Median age at HL diagnosis was 34 years (range 17–77); 129 (51%) were male, 49% had advanced stage disease, while localized presentations were favourable: 25% and unfavourable: 26% by NCIC criteria. 77 (30%) patients had a smoking history, 121 (48%) received thoracic radiation for HL and 27(11%) had underlying lung disease. BPT was observed in 29 (11%) patients, with a median onset time of 4 months from initiation of ABVD. Bleomycin was discontinued in 20/29 patients (69%) and 19/29 (66%) patients were treated for BPT with corticosteroids (median duration: 11 weeks (range 3–23)).On bivariate analysis, risk factors associated with increased risk of BPT include age ≥45 years (55% BPT vs 28% non-BPT, p=0.003), G-CSF use (90% vs.71%, p=0.043), and ECOG PS ≥2 (24% vs.10%, p=0.02). On multivariable analysis, age ≥45 years (HR=3.1, p=0.005) and G-CSF use (HR=3.5, p=0.045) remained as independent predictors of BPT development. There was no sufficient evidence of a statistically significant difference in pulmonary risk factors in patients with or without BPT. There was a trend towards lower baseline serum albumin in BPT group, although this did not reach statistical significance (p=0.052).At a median follow-up of 5 years, OS and PFS for all 253 pts were 88% and 82%. 30 pts died due to disease progression (15), treatment-related complications (5; 3 secondary malignancies), and other causes (4). Only 3 deaths occurred among the 29 pts with BPT (2 unrelated, 1 from concomitant BPT and sepsis with multiorgan failure). On multivariable analysis, age≥60 (HR 3.7 for OS, p=0.003; HR 2.5 for PFS, p=0.019) and ECOG PS≥2 (HR 3.1 for OS, p=0.009; HR 3.0 for PFS, p=0.003) were identified as predictors of inferior survival in advanced stage HL. Increased age was associated with inferior OS (HR 1.05, p=0.031) and PFS (HR 1.06, p=0.004) in limited stage HL. Development of BPT had no significant impact on CR (97% BPT vs. 89% in non-BPT, p=0.77), 5-year OS (93% vs. 87%, p=0.80) or PFS (83% vs. 82%, p=0.98) in multivariate analysis. Bleomycin discontinuation (66 pts, 27%; 20 due to BPT, 5 skin toxicity, 36 non-BPT respiratory symptoms, 5 other) had no impact on CR rate (88% vs. 91%, p=0.19), 5-year PFS (81% vs. 83%, p=0.98), or 5-year OS (85% vs. 89%, p=0.89). Conclusions:The incidence of BPT in this series is low at 11%. Our study confirms advanced age and G-CSF usage as risk factors for BPT and identified poor PS as an independent predictor of BPT. In contrast to some prior studies, we demonstrate similar OS and PFS for pts who developed BPT or had bleomycin discontinued. This may be attributed to earlier recognition and management for suspected BPT in the past decade. Disclosures:Kukreti:Celgene: Honoraria; Ortho Biotech: Honoraria; Roche: Honoraria. Crump:Millennium Pharmaceuticals: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Ortho Johnson & Johnson: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity’s Board of Directors or advisory committees.

Treatment of Hodgkin lymphoma with adriamycin, bleomycin, vinblastine and dacarbazine without routine granulocyte-colony stimulating factor support does not increase the risk of febrile neutropenia: a prospective cohort study

Although patients with Hodgkin lymphoma treated with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy frequently develop neutropenia, febrile neutropenia is uncommon. Three retrospective trials reported that ABVD could be safely administered without dose delays or granulocyte-colony stimulating factor (G-CSF) support. We retrospectively reviewed the charts of 89 patients treated with ABVD and found that the incidence of febrile neutropenia was 0.5% (five of 927 treatments). This prompted a change to our institutional policy so that patients receiving ABVD no longer receive routine G-CSF for uncomplicated neutropenia. We then prospectively assessed the safety of this policy change. Thirty-three patients received a total of 327 ABVD treatments, 185 (57%) of which were administered with a neutrophil count <1.5 × 109/L. Febrile neutropenia occurred in 2/33 patients (6%), complicating 0.6% of chemotherapy treatments (2/327). Eliminating routine G-CSF saved $10 241 per patient. Omission of G-CSF for uncomplicated neutropenic patients receiving ABVD for Hodgkin lymphoma is cost-saving and safe.

Late Relapses following High-Dose Autologous Stem Cell Transplantation (HD-ASCT) for Hodgkin’s Lymphoma (HL) in the ABVD Therapeutic Era

Salvage chemotherapy followed by high-dose autologous stem cell transplantation (HD-ASCT) is the standard of care for patients who have relapsed or refractory Hodgkin's lymphoma (HL). Few trials have had long-term follow-up post-HD-ASCT in the ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine) era of treatment. We reviewed 95 consecutive patients who received HD-ASCT for relapsed or refractory HL following ABVD failure between 1990 and 2006 at the University of Rochester. Median follow-up for survivors was 8.2 years. All patients received HD-ASCT following upfront ABVD (or equivalent) failure. At 5 years, overall survival (OS) and event-free survival (EFS) were 54% and 37%, respectively. In total, 54 patients have died; 37 of these patients died directly of HL. Notably, there were 19 deaths >3 years post-HD-ASCT and 13 of these late deaths are directly attributable to HL. Furthermore, there were 51 documented relapses, 9 of which occurred >3 years post-HD-ASCT. In contrast to other studies, we did not observe a plateau in EFS following transplantation. Patients appear to be at continuous risk of recurrence beyond 3 years after HD-ASCT. Our results emphasize the importance of long-term follow-up for both toxicity and recurrence, and have important implications in defining success of posttransplantation maintenance strategies.

ACR Appropriateness Criteria® on Hodgkin's Lymphoma-Unfavorable Clinical Stage I and II

Combined-modality therapy, consisting of chemotherapy followed by radiation therapy (RT), represents the standard of care for most patients with unfavorable-prognosis early-stage Hodgkin's lymphoma. The most widely accepted chemotherapy regimen is ABVD (Adriamycin, bleomycin, vinblastine, and dacarbazine); however, recent trials have evaluated other regimens such as BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) and Stanford V. After chemotherapy, the standard radiation field is involved-field RT, although there is increasing interest now in involved-node RT. The authors review recent trials on chemotherapy and RT for unfavorable-prognosis early-stage Hodgkin's lymphoma. This article presents illustrative clinical cases, with treatment recommendations from an expert panel of radiation oncologists and medical oncologists.

Prognostic value of interim FDG PET/CT in Hodgkin’s lymphoma patients treated with interim response-adapted strategy: comparison of International Harmonization Project (IHP), Gallamini and London criteria

Interim 2-[(18)F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) has shown to be an accurate predictor of prognosis in Hodgkin's lymphoma (HL). However, FDG PET response criteria are a matter of ongoing debate. The aim of this study was to confirm the prognostic value of interim PET/CT in HL patients treated with an interim response-adapted strategy and to compare the respective performances of different published criteria. Newly diagnosed patients with HL underwent interim PET/CT after four courses of Adriamycin, bleomycin, vinblastine and dacarbazine (ABVD). The treatment strategy was adapted according to prognostic factors at diagnosis and interim PET/CT and CT results. PET images were prospectively interpreted visually: a negative result was defined as no residual uptake above local background. All other findings were considered as positive. Retrospectively, interim PET/CT was analysed according to International Harmonization Project (IHP), Gallamini and London criteria The analysis included 90 patients; 6 of 31 patients with positive interim PET/CT and 7 of 59 patients with negative interim result presented treatment failure. The negative predictive value (NPV) and positive predictive value (PPV) for predicting 2-year progression-free survival (PFS) was 95 and 16%, respectively. With the other criteria, NPV remained very high (from 95 to 96%). The PPV increased from 19 to 45% according to the threshold used. Interim PET/CT was significantly correlated with PFS with Gallamini (p = 0.01) and London criteria (p < 0.0001). Our study confirms the high NPV of interim PET/CT for predicting treatment outcome in HL and a probably better prognostic value using a higher threshold for positivity even after four cycles of chemotherapy as used in Gallamini and London criteria.

The Management of Classical Hodgkin's Lymphoma: Past, Present, and Future.

The management of classical Hodgkin's lymphoma (CHL) is a success story of modern multi-agent haemato-oncology. Prior to the middle of the twentieth century CHL was fatal in the majority of cases. Introduction of single agent radiotherapy (RT) demonstrated for the first time that these patients could be cured. Developments in chemotherapy including the mechlorethamine, vincristine, procarbazine and prednisolone (MOPP) and Adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) regimens have resulted in cure rates of over 80%. Even in relapse, CHL patients can be salvaged with high dose chemotherapy and autologous haematopoietic stem cell transplantation (ASCT). Challenges remain, however, in finding new strategies to manage the small number of patients who continue to relapse or progress. In addition, the young age of many Hodgkin's patients forces difficult decisions in balancing the benefit of early disease control against the survival disadvantage of late toxicity. In this article we aim to summarise past trials, define the current standard of care and appraise future developments in the management of CHL.

The Past: What We Have Learned in the Last Decade

Hodgkin lymphoma (HL) has become a curable malignancy for most patients during the last decades. However, many controversies still exist on the optimal strategy of how to cure our patients. The key question is how to balance the risks and toxicities of chemotherapy and radiotherapy against the need for a definite treatment for early or advanced-stage HL patients. However, although many studies have been conducted and reported during the past decade, interpretation of their results and treatment recommendations might vary significantly in different countries. For example, early-stage HL might be divided into two different subgroups: early favorable and early unfavorable or not. Treatment of early-stage HL might include radiotherapy ("combined modality") or not. Depending on the extent of radiotherapy, the schedule and number of chemotherapy cycles are also questioned. For advanced-stage HL, the situation is not much different. Compared with ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine), the more aggressive escalated BEACOPP regimen (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone) is highly effective, but also raises concern due to excessive toxicity. Thus, there is a controversy about the standard of care for advanced HL patients. Because no mature results comparing these approaches with each other are currently available, it remains our duty to share the preliminary information with our patients and to figure out the most appropriate individual treatment strategy. Of course, the discussion of these issues is influenced by experiences and preferences. In contrast, in this article, we will try to focus on the available scientific evidence regarding the first-line treatment of HL. Of course, focusing on the last decade necessarily exclude the most recent results from ongoing studies. Thus, even though this article comprises treatment recommendations for HL patients, the best treatment certainly still is within properly designed prospective clinical trials.

Prognostic significance of mid- and post-ABVD PET imaging in Hodgkin's lymphoma: the importance of involved-field radiotherapy

BackgroundAlthough positron emission tomography (PET) response to chemotherapy (CT) has prognostic significance in Hodgkin's lymphoma (HL), it is unclear whether patients with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG)–PET positivity during and/or after CT can be rendered disease free with consolidative involved-field radiotherapy (IFRT). MethodsPatients with HL treated with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD)-based CT and radiotherapy (RT) at our institution from January 2000 to March 2007 were eligible. All patients had either a post-treatment PET or PET–CT before initiation of RT or a negative midtreatment PET or PET–CT. The primary end point was failure-free survival (FFS) for patients with and without residual FDG avidity after ABVD. The treatment outcome of patients with interim PET positivity during CT was also reported. ResultsSeventy-three patients were included in this study. Twenty patients (out of 46) were PET positive on interim PET, and 13 patients (out of 73) were PET positive at the conclusion of CT. At a median follow-up of 3.4 years for surviving patients, the 2-year FFSs for patients PET-negative versus PET-positive disease after ABVD were 95% and 69%, respectively (P<0.01). On bivariable Cox regression, post-ABVD positivity (hazard ratio 4.8, P=0.05) was predictive of disease recurrence after controlling for bulky disease. Of the 20 patients with interim PET positivity, three recurred, with a 2-year FFS of 85%. Among the 13 patients with interim PET positivity, but became PET negative at the completion of CT, the 2-year FFS was 92%. ConclusionSixty-nine per cent of patients with residual FDG avidity after ABVD were free of disease after consolidative RT, indicating a majority of patients with persistent lymphoma can be cured by sterilizing this PET-positive disease.

Retrieval of immature oocytes after chemotherapy for Hodgkin's disease and prolonged ovarian down-regulation with gonadotropin-releasing hormone agonist

To describe isolation and in vitro maturation of primary oocytes from the ovarian cortex in the presence of hypothalamic pituitary down-regulation. Case report. Tertiary care university-affiliated hospital. An 18-year-old patient was given treatment with the ABVD (Adriamycin, bleomycin, vinblastine, and dacarbazine) protocol for Hodgkin's disease. She underwent ovarian tissue cryopreservation while being cotreated with GnRH agonist because of disease relapse. Laparoscopic oophorectomy, ovarian tissue cryopreservation, and in vitro maturation of primary oocytes. Maturation of primary oocytes isolated from the medium used for preparation of ovarian tissue. Twenty-one immature germinal vesicle-stage oocytes were isolated from the medium of dissection. All were incubated in in vitro maturation medium, and five were maturated and frozen. The fact that germinal vesicle-stage oocytes were present in our patient's medium despite hormonal down-regulation demonstrates that GnRH agonist does not completely inhibit antral follicle development.