The optimal pretransplant regimen for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) in patients ≥55 years of age remains to be determined. The myeloablative reduced-toxicity 4-day regimen IV busulfan (Bu) (130 mg/m2)-IV fludarabine (Flu) (40 mg/m2) is associated with low morbidity and mortality. We analyzed 79 patients ≥55 years of age (median, 58 years) with AML (n=63) or MDS (n=16) treated with IV Bu-Flu conditioning regimens between 2001 and 2009 (median follow-up, 24 months). The patients who received this regimen had a good performance status. The 2-year overall survival rates for patients in first complete remission (CR1), second CR (CR2), refractory disease and for all patients at time of transplantation were 71%, 44%, 32%, and 46%, respectively; 2-year event-free survival rates for patients in CR1, CR2, or refractory disease at time of transplantation and for all patients were 68%, 42%, 30%, and 44%, respectively. One-year transplant-related mortality (TRM) rates for patients who were in CR or who had active disease at the time of transplantation were 19% and 20%, respectively. Grade II-IV acute graft-versus-host disease was diagnosed in 40% of the patients. Our results suggest that age alone should not be the primary reason for exclusion from receiving myeloablative reduced-toxicity conditioning with IV Bu-Flu preceding transplantation in patients with AML/MDS.
Progressive multifocal leukoencephalopathy (PML) is a central nervous system (CNS) disease usually observed in immunodeficient patients, especially human immunodeficiency virus (HIV)-positive, caused by John Cunningham virus. This infectious complication has been described in many HIV-negative hematological patients, especially affected by lymphoproliferative diseases. PML has been observed after both chemotherapy and bone marrow transplantation and, recently, in association with rituximab. Diagnosis can be complicated, and often a CNS biopsy is required. Current treatment approaches are not effective in both HIV-positive and HIV-negative patients, and the outcome remain very poor in the majority of cases, even after combination therapies. We report three cases of PML in hematological patients, treated respectively with conventional chemotherapy and autologous and haploidentical transplantation, and review the literature on PML. All of them received rituximab, which has recently been in the focus of a Food and Drug Administration warning.
Purpose
Despite recent advances, multiple myeloma remains incurable and most patients eventually develop progressive disease. Allogeneic hematopoietic stem cell transplantation (allo HCT) offers a potentially curative option in 10–20% of patients with relapsed or refractory disease. We evaluated the outcome of patients undergoing allo HCT with reduced-intensity conditioning (RIC) for relapsed and/or refractory myeloma at our institution.
Methods
Fifty-one patients with heavily pretreated, relapsed myeloma, who received RIC allo HCT between 1996 and 2006, were included in this analysis.
Results
Median time from diagnosis to allo HCT was 34 months. Median follow-up in surviving patients was 27 months (3–98). Cumulative transplant-related mortality (TRM) at 1 year was 25%. Progression-free survival (PFS) and overall survival (OS) at 2 years were 19% and 32%, respectively. The incidence of grade II-IV acute or chronic graft-vs-host disease (GVHD) was 27% and 47%, respectively. At the time of this analysis, 12 patients (24%) were alive 7 of whom (14%) were in remission for up to 6 years after allo SCT. A lower β2 microglobulin (<3.3) and a prior autotransplant predicted a lower NRM, longer PFS and OS.
Conclusion
Allo HCT with RIC regimens is associated with acceptable toxicity and durable remission and survival in relapsed or refractory myeloma. Use of RIC allo HCT earlier in the course of the disease may offer greater benefit.
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