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Buparlisib is an orally available pan-Class I PI3K inhibitor, that is more potent than idelalisib in vitro. Its distinct toxicities include hyperglycemia, hypertension, and mood disturbance. IND216...

This study compares the clinical outcomes of 60 consecutive patients who received an allogeneic blood or marrow stem cell transplant (BMT) from one Human Leukocyte Antigen (HLA) mismatched related donors with those of 120 matched patients who had HLA identical sibling donors. The control patients were matched for diagnosis, disease status, conditioning regimen, and age at BMT. All patients received standard CYA and MTX for GVHD prophylaxis. The probability of overall survival (OS) at 5 years was 35% in the study group compared to 56% in the control group. The relapse rates and acute GVHD rates did not differ between the two groups. Graft failure was a significant problem in the study group compared to the control group (13 vs. 0%, p < 0.0001). All cases of graft failure occurred in patients with a mismatch in the host-versus-graft direction. BMT-related deaths were also increased in the study group. Forty percent of deaths were caused by infection in the study group vs. 19% in the control group (p < 0.01). In conclusion, the OS of patients receiving marrow/stem cells from one antigen mismatched related donors was inferior to that of controls with HLA-identical related donors. There was an increase in mortality related to infections occurring in the setting of an increased frequency of graft failure in these patients.

Optimal high dose conditioning and relative roles of autologous stem cell transplantation (autoSCT) or allogeneic (alloSCT) for indolent lymphoma are uncertain.A prospective phase II study evaluated autoSCT and alloSCT depending on availability of sibling donor after uniform rituximab, ifosfamide, carboplatin, etoposide (RICE) re-induction and novel myeloablative fludarabine, busulfan (FluBu) conditioning for patients with mantle cell lymphoma in first remission or first relapse, or indolent lymphoma in first or second relapse.The 68 patients (autoSCT, 36; syngeneic [syn], 1; alloSCT, 31) who were accrued had a 10-month median progression-free survival (PFS) after their last chemotherapy treatment. After RICE, the overall response rate was 69%, and 24 of 39 patients (62%) cleared marrow of lymphoma. Treatment-related mortality at 100 days and 1 year after FluBu were both 0% post-auto/synSCT, but were 6% and 26% post-alloSCT, respectively. At a median follow-up of 60 months, the respective 5-year overall survival and PFS rates were 71% and 46% for auto/synSCT, and were 58% and 47% for alloSCT. Quality of life assessment 1-year post-SCT favoured auto/synSCT.The protocol was feasible, FluBu was well-tolerated, and both auto/synSCT and alloSCT conferred similar 5-year PFS following the RICE-FluBu protocol.

We analyzed the outcomes of 24 consecutive patients aged ≥60 years with poor-prognosis myelodysplastic syndrome or acute myeloid leukemia undergoing transplantation with nonmyeloablative conditioning using fludarabine (125 mg/m2) and low-dose total body irradiation (2 Gy) followed by allogeneic peripheral blood stem cell grafts from HLA-identical sibling donors. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and mycophenolate mofetil. The median age of the patients was 64 years (range, 60-71 years). In addition to age, 88% of patients had 1 or more adverse biological features of the disease. With a median follow-up of 21 months, 12 patients are alive, 11 of whom are disease free. The probabilities of 2-year overall and progression-free survival were 52% and 44%, respectively. The cumulative probabilities of relapse and of acute and chronic GVHD were 27%, 45%, and 74%, respectively. Nonrelapse mortality at 100 days and 2 years was 8% and 25%, respectively. Of the 15 patients with extensive chronic GVHD, 1 patient relapsed. These data suggest that nonmyeloablative stem cell transplantation is a feasible treatment option in patients aged ≥60 years with poor-prognosis myelodysplastic syndrome or acute myeloid leukemia. The reasonable disease control with nonmyeloablative transplantation in this high-risk group of patients merits further investigation.