Summary Diffuse large B‐cell lymphoma (DLBCL) occasionally presents with circulating malignant cells. The clinical characteristics and long‐term outcomes of these patients have not been described. Twenty‐nine newly diagnosed DLBCL presenting in leukaemic phase were identified between 1996 and 2010, at two institutions. Median age was 48 years, and patients presented with leucocytosis, high lactate dehydrogenase levels, B symptoms, and high International Prognostic Index score. Extra nodal site involvement was observed in all patients and affected the bone marrow (100%), spleen (62%), pleura/lung (41%), liver (21%), bone (17%), bowels (7%) and cerebrospinal fluid (14%). Blood lymphomatous cells co‐expressed CD19, CD20, CD22, CD38, CD45, HLA‐DR and FMC7 in >90%, and kappa or lambda light chain restriction in >50%. Ninety per cent received rituximab and anthracycline‐based chemotherapy. Overall, remission was complete in 54% and partial in 31%; 15% had resistant disease. Median follow‐up was 47 months; 13 (45%) patients remain alive in complete remission. Median progression‐free and overall survivals were 11·5 and 46·7 months, respectively. In summary, patients with DLBCL in leukaemic phase present with high tumour burden and frequent involvement of extra nodal sites. In this uncommon DLBCL subgroup, anthracycline‐based regimens with rituximab are associated with early morbidity and mortality, but yield approximately 50% 4‐year survival.
2947 Poster Board II-923 Introduction: DLBCL occasionally presents in leukemic phase, and the prognostic significance of circulating lymphoma cells is unknown. We herein report characteristics and outcomes of newly diagnosed DLBCL presenting in leukemic phase at 2 Institutions. Methods: Flow cytometry database analysis and retrospective chart reviews were carried out with IRB-approval for cases accrued between 2001 and 2008. Leukemic phase DLBCL patients were matched on a 3:1 basis with control DLBCL with no circulating lymphoma cells based on IPI, year of diagnosis, and age ± 10 years. Results: 18 patients, median age 48 years (range 34-80), ECOG PS-1 (22%), 2(38%) and 3(40%), and IPI - 3(56%), 4(40%) and 5(4%) presented in leukemic phase. Extranodal sites included bone marrow (100%), spleen (83%), pleura (61%) and CSF (22%). 61% had B symptoms, and LDH was 6xULN (range, 1-56). WBC was 13,000/microL (range, 7,100-127,400), with 50% lymphoma cells (range, 2-92); these cells were immunophenotypically similar to those in the histologically confirmed DLBCL node, and co-expressed CD19, CD20, CD22, CD38, CD45, HLA-DR and FMC7 in >90% of cases, and kappa or lambda light chain restriction in > 50%. Karyotype was abnormal and complex in 61%. One patient expired before treatment began. Treatment consisted of R-CHOP (10), R-HCVAD (6), and single agent rituximab (1). 8 (44%) achieved CR (5 R-HCVAD and 3 R-CHOP), 5 (28%) PR, and 4 (22%) had resistant disease. 1 patient was autografted in CR1 and remains in remission. With a median follow-up of 32 months, 2 relapsed in leukemic phase, 1 of whom achieved CR2, but relapsed at the time of conditioning for a consolidative allograft. 10 (56%) patients died from progressive disease, 2 (11%) were lost to follow-up and 6 (33%) remain alive in remission. Overall (Panel A) and progression-free (Panel B) survival curves the 18 leukemic (solid line) and 54 non-leukemic phase (dashed line) DLBCL are depicted in the Figure. Conclusion: DLBCL presenting with circulating lymphoma cells is associated with chemo-resistance (44% CR) and poor outcomes with the exception of those who achieve complete remission. These patients are candidates for alternative therapies. Disclosures: Kaufman: Millenium: Consultancy; Genzyme: Consultancy; Celgene: Consultancy, Research Funding; Merck: Research Funding. Lonial:Millennium: Consultancy, Research Funding; Celgene: Consultancy; BMS: Consultancy; Novartis: Consultancy; Gloucester: Research Funding. Armitage:Eisa: Consultancy; Allo: Consultancy; Ziopharm: Consultancy.
4103 Introduction The addition of IM to hyper-CVAD led to higher rates and longer duration of complete remissions in Ph+ ALL. The purpose of this study is to report single institution experience with IM-HCVAD followed by maintenance IM or allogeneic transplantation in newly diagnosed adult Ph+ ALL treated between 10/02 and 08/08. Methods IRB-approved retrospective analysis of the institutional hematological database. Results Thirty-three patients, median age 51 (22-72), with 8 (24%) older than 60, presented with a median WBC of 24,000/mm3 (range, 2-200) and LDH of 2.6 ULN (1.3-11). Four (12%) had extra-medullary/CSF leukemia. Patients received a median of 7 (range, 1-8) cycles of IM-HCVAD followed by maintenance IM +/- POMP as tolerated (Blood 2004;103:4396-4407). After 2 cycles, 1 patient had primary refractory disease and expired, and 32 (97%) achieved complete hematological and cytogenetic remission. Twenty-four of 32 (75%) subsequently achieved complete molecular remission (CMR). Among those who achieved CMR, 6/24 relapsed with preceding loss of CMR in 4. Four of 8 who did not achieve CMR relapsed. One patient in CR was lost to follow-up after induction. Thirteen (39%) were allografted in CR1 using TBI-based myeloablative (9) or non-myeloablative (4) conditioning and 18 received maintenance IM-based therapy. With a median follow-up of 18.3 months (range, 4.4-76), 10 patients (32%) relapsed (1 post-transplant and 9 during IM maintenance) and received salvage therapy leading to CR2 in 4, of which 1 was successfully allografted, and 3 remain in CR2 with a follow-up of 20, 36, and 60 months. Eleven patients died (6 from GVHD/infection, and 5 from relapsed refractory leukemia). For the 13 allograft recipients in CR1 disease-free (DFS) and overall survival (OS) were 15, and 18 months; and 15 months and 20 months for the 18 IM maintenance patients, respectively (Figure). WBC > 30,000/mm3 and residual disease detected by flow cytometry after 2 cycles were associated with decreased OS (p < 0.03). A trend for lower survival was noted among African American patients (p= 0.07). Conclusion The addition of IM to hyper-CVAD is associated with high rates of CR (97%) in newly diagnosed Ph+ ALL. In this relatively small cohort with a short follow-up, peripheral blood PCR did not predict outcomes. Ph+ALL patients are candidates for novel maintenance regimens. Disclosures: Off Label Use: Imatinib combined with the hyper-CVAD chemotherapy. Khoury:Novartis Oncology: Honoraria.
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