High dose chemotherapy and autologous stem cell transplantation in relapsed or refractory Hodgkin lymphoma: emerging questions, newer agents, and changing paradigm

Primary treatment for adult and pediatric patients with Hodgkin lymphoma [HL] using current multiagent anthracycline-based chemotherapy with or without radiation therapy will cure approximately >70% of the patients; >95% for early stage with a favorable risk profile and 70-75% with advanced stage and high risk features. Managing refractory and relapsed disease, however, remains a challenge. High dose chemotherapy [HDC] and autologous stem cell transplantation [auto-SCT] can salvage 40-70% of patients with relapsed or refractory HL. Two randomized trials in relapsed and refractory patients showed superior progression free survival. This presentation addresses some of the salient differences and changes in the management that have evolved over the last decade and have either already affected, or are likely to affect the outcome of HDC auto-SCT. The following will discussed. 1. Historic trials and other emerging issues impacting the outcome of HDC auto-SCT. 2. Changes in the primary treatment and response adapted therapy. 3. Evaluation and validation of prognostic factors at the time of first failure. 4. Selection of salvage chemotherapy. 5. Conditioning regimens. 6. Consolidation after HDC auto-SCT. 7. Management of failures of HDC auto-SCT. 8. Availability of financial resources in various healthcare systems. Enrolment in clinical trials should be encouraged

Untreated primary thyroid lymphoma in an elderly woman

A 92- year-old otherwise healthy female was diagnosed in another institution with thyroid lymphoma on fine needle aspirate [FNA] five years back. The patient repeatedly refused further management. Due to the rapid increase in the size of her tumor, shortness of breath and stridor, she was transferred to our institution and required intubation in the intensive care unit. She had 30x15 cm neck mass extending bilaterally and to the upper chest with an engorged neck and chest veins [Figure 1, A and B; Figure 2A]. Her thyroid-stimulating hormone was 1109 mU/ L [normal range, 0.27 to 4.2 mU/L]. Flow immunophe-notyping from the thyroid FNA specimen confirmed a CD19, CD20, and CD22 expressing monoclonal B-cell population, high forward and side scatter showing surface kappa light chain restriction. CD 10 and CD5 were not co-expressed. These features and morphology were consistent with a large B-cell lymphoma. She received cyclophosphamide 500 mg intravenously and one dose of vincristine 2 mg intravenously and dexamethasone 40 mg intravenously for 5 days. Her tumor was reduced by 70% after five days. Her shortness of breath and stridor increased and chest x-ray showed infiltrates and then aspiration pneumonia [Figure 2B. She developed febrile neutropenia, Klebsiella pneumoni-at bacteremia, deteriorated rapidly, developed multiple organ system failure and died fourteen days after receiving chemotherapy

Improved survival with combined chemo-radiotherapy in primary central nervous system lymphoma

Primary CNS lymphoma [PCNSL] is an aggressive primary brain tumor. Cranial irradiation alone rarely results in long term disease control or prolonged survival. We retrospectively analyzed data on the effect of adding high-dose methotrexate [HDMTX] prior to whole brain irradiation [WBI]. All patients with PCNSL diagnosed and managed during 1991-2004 were identified and demographic characteristics, prognostic factors, treatment and outcome were reviewed. Of 62 patients, 10 were excluded [4 had WBI < 40 Gy and 6 had no treatment]. Radiation alone was considered curative with a dose > 40 Gy. Combined modality therapy included 3-4 cycles of HDMTX [3g/m2] followed by WBI. Of 52 patients analyzed for outcome, 36 had WBI [dose > 40 Gy], 16 received 3-4 cycles of HDMTX followed by WBI [combined modality therapy [CMT]]. Median age was 48.2 years; 42 years in the CMT group, 51 years in WBI. Patient characteristics were comparable between two groups except for higher multifocal tumor in the CMT group [92% vs. x22%, P=.029]. Median follow up was 12.83 +/- 6.4 months. The hazard ration for an event was 0.64 [95% CI, 0.52-0.98] and for death 0.58 [95% CI, 0.48-0.92], both in favor of CMT. Univariate regression analysis using one-way analyses of variance [ANOVA] and multivariate Cox regression analysis for prognostic factors including age [< 60 vs. >60], ECOG PS [0-2 vs. 3-4], extent of surgery [biopsy vs. debulking], solitary vs multifocal tumor and dose of radiation therapy [>50Gy vs. >50 Gy] failed to identify any prognostic factor. This retrospecitive comparison supports phase II trial results that indicate that high-dose methotrexate followed by WBI in PCNSL improves outcome