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GABRIELL was a phase II single-arm study to evaluate the efficacy and safety of obinutuzumab plus bendamustine for relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Seventy-two patients with active disease received treatment for up to six 28-day cycles. Overall response rate was 78.6% with a median progression-free survival (PFS) of 26 months, and overall survival (OS) not reached at the end of follow-up (36 months). Undetectable measurable residual disease (≤0.01%; 36.4% in bone marrow and 53.4% in peripheral blood) correlated with a significantly longer PFS and OS (vs. >0.01). Common grade ≥3 adverse events (76.4%) were neutropenia (58.3%), thrombocytopenia (26.4%) and febrile neutropenia (11.1%). TP53 disruption was the only independent predictive factor for response (Hazard ratio; HR: 0.228). Unmutated immunoglobulin heavy chain variable region (HR: 16.061) was a negative prognostic factor for PFS. In conclusion, the combination of obinutuzumab plus bendamustine is an active and generally adequately-tolerated treatment for R/R CLL. [ABSTRACT FROM AUTHOR]

Objective, Methods, and Results. To reduce the period of posttransplant neutropenia and related early morbidity and mortality of cord blood (CB) transplants, we assessed the feasibility of co-infusion of a low number of highly purified peripheral blood CD34+ cells from a related haploidentical donor with a CB graft. Between March 1999 and May 2002, 11 patients with high-risk hematologic malignancies were transplanted using this strategy. The seven patients who received a haploidentical peripheral blood graft and a CB graft from a sibling (6) or the father (1) had prompt recovery (9–17 days, median 10) of the absolute neutrophil count (ANC) to greater than 0.5×109/L. Analysis of DNA polymorphisms showed initial predominance of the haploidentical genotype both in granulocytes and in mononuclear cells, and subsequent progressive replacement by cells of CB genotype until final complete CB chimerism was achieved by patients who survived for sufficient periods of time. The four patients who received maternal haploidentical cells had no significant contribution of these to blood leukocytes, although complete CB chimerism was achieved by three of them and two reached engraftment of the CB on days +20 and +36. Morbidity due to early bacterial or fungal infections was remarkably low in patients with prompt ANC recovery.Conclusion. Our data show that co-infusion of a CB unit and a low number of haploidentical CD34+ cells may result in a shortened period of posttransplant neutropenia. This is likely the result of prompt and transient engraftment of the haploidentical hematopoietic stem cells that may provide the patient antimicrobial protection until the later engraftment of the CBhematopoietic stem cells. [Copyright &y& Elsevier]

Unlabelled: OBJECTIVE, METHODS, AND RESULTS: To reduce the period of posttransplant neutropenia and related early morbidity and mortality of cord blood (CB) transplants, we assessed the feasibility of co-infusion of a low number of highly purified peripheral blood CD34+ cells from a related haploidentical donor with a CB graft. Between March 1999 and May 2002, 11 patients with high-risk hematologic malignancies were transplanted using this strategy. The seven patients who received a haploidentical peripheral blood graft and a CB graft from a sibling (6) or the father (1) had prompt recovery (9-17 days, median 10) of the absolute neutrophil count (ANC) to greater than 0.5 x 10(9)/L. Analysis of DNA polymorphisms showed initial predominance of the haploidentical genotype both in granulocytes and in mononuclear cells, and subsequent progressive replacement by cells of CB genotype until final complete CB chimerism was achieved by patients who survived for sufficient periods of time. The four patients who received maternal haploidentical cells had no significant contribution of these to blood leukocytes, although complete CB chimerism was achieved by three of them and two reached engraftment of the CB on days +20 and +36. Morbidity due to early bacterial or fungal infections was remarkably low in patients with prompt ANC recovery., Conclusion: Our data show that co-infusion of a CB unit and a low number of haploidentical CD34+ cells may result in a shortened period of posttransplant neutropenia. This is likely the result of prompt and transient engraftment of the haploidentical hematopoietic stem cells that may provide the patient antimicrobial protection until the later engraftment of the CB hematopoietic stem cells.

Background and Objectives: Patients with B-cell lymphoma can be induced to mount a specific immune response against the individual idiotypic determinants expressed in their tumor cells. This form of active immunotherapy is now under evaluation in the clinical setting. We evaluated the feasibility and effectiveness of this kind of immunotherapy in a group of patients with low-grade lymphoma, which included two cases of bi/triclonal lymphoma., Design and Methods: Nine patients with a histopathologic diagnosis of follicular non-Hodgkin's (NHL) low-grade B-cell lymphoma were initially selected for this disease-free survival study. Idiotypic proteins were recovered by somatic fusion of the tumor cells and their identity with the tumor idiotype determined by molecular methods. The patients received the vaccine consisting of their tumor Ig protein coupled to keyhole limpet hemocyanine and were observed for toxicity, anti-idiotypic immune response, clinical outcome and circulating t(14;18)+ tumor cells., Results: The median duration of follow-up was 40 (10-64) months from the initiation of immunotherapy. Tumor regression was detected in two patients. No tumor progression was observed in the other patients. Eight patients generated specific anti-idiotypic antibodies and 3 out of five were cleared of circulating t(14;18)+ cells., Interpretation and Conclusions: Induction of tumor-specific anti-idiotypic immune responses may be of benefit to patients affected by low-grade B-cell NHL. Our results are in line with those previously reported and call attention to the issue of tumor clonality in this kind of treatment.