Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
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Biol. Blood Marrow Transplant. · Feb 2009
Clinical TrialTreatment of acute leukemia with unmanipulated HLA-mismatched/haploidentical blood and bone marrow transplantation.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains one of the best therapeutic options to cure acute leukemia (AL). However, many patients have no human leukocyte antigen (HLA)-matched donor. Recently, we developed a new method for HLA-mismatched/haploidentical transplantation without in vitro T cell depletion (TCD). ⋯ The 3-year probability of LFS for acute myelogenous leukemia (AML) was 70.7% and 55.9%, and for acute lymphoblastic leukemia (ALL) it was 59.7% and 24.8% in standard-risk and high-risk groups, respectively. Lower LFS were associated with diagnosis of acute leukemia in the high-risk group (P= .001, relative risk [RR], 95% confidence interval [CI]: 2.94[1.535-5.631]) and the occurrence of aGVHD of grades 3 and 4 (P= .004). HLA-mismatched/haploidentical HSCT was feasible with unmanipulated blood and bone marrow harvest.
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Biol. Blood Marrow Transplant. · Jan 2009
Allogeneic stem cell transplantation for adults with myelodysplastic syndromes: importance of pretransplant disease burden.
Allogeneic stem cell transplantation is the only known curative therapy for myelodysplastic syndromes (MDS). We present the transplant outcomes for 84 adult MDS patients, median age 50 (18-69 years), undergoing allogeneic hematopoietic stem cell transplantation (HSCT) at the University of Minnesota between 1995 and 2007. By WHO criteria 35 (42%) had refractory anemia with excess blasts (RAEB-1 or 2), 23 (27%) had refractory cytopenia with multilineage dysplasia (RCMD) or RCMD and ringed sideroblasts (RCMD-RS), and the remaining 26 (31%) had refractory anemia (RA), myelodysplastic syndrome-unclassifiable (MDS-U), chronic myelomonocytic leukemia (CMML), myelodysplastic/myeloproliferative disease (MDS/MPD), or myelodysplastic syndrome-not otherwise specified (MDS-NOS). ⋯ For patients entering transplant in CR or with <5% blasts, prior treatment to reach this level did not impact rates of relapse or transplant-related mortality when all patients were analyzed; however, when broken down by conditioning intensity, there was a trend toward improved DFS in those NMA patients who were pretreated. Finally, 1-year DFS was similar using related donor peripheral blood stem cell (PBSC)/marrow, URD marrow, or UCB grafts. These data suggest that (1) blast percentage <5% at HSCT is the major predictor of improved DFS and relapse and prior treatment to reach this disease status may have value in leading to improved DFS; (2) MA conditioning is associated with lower relapse risk, particularly in patients with CR or <5% blasts, but is not able to overcome increased disease burden; (3) NMA conditioning yields equivalent TRM, DFS, and OS, and is reasonable in patients unsuited for MA conditioning; (4) the donor sources tested (PBSC, bone marrow [BM], or UCB) yielded similar outcomes.
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Biol. Blood Marrow Transplant. · Jan 2009
Clinical TrialHematopoietic cell transplantation from an HLA-mismatched familial donor is feasible without ex vivo-T cell depletion after reduced-intensity conditioning with busulfan, fludarabine, and antithymocyte globulin.
To extend the use of allogeneic hematopoietic cell transplantation (HCT) to patients without an HLA-matched donor, we investigated HCT from a related donor with 1 fully mismatched HLA-haplotype after conditioning with busulfan in reduced-dose, fludarabine, and antithymocyte globulin. Hematopoietic cells were collected from the donors via leukapheresis after mobilization and infused without further manipulation. Cyclosporin and methotrexate were administered for graft-versus-host disease (GVHD) prophylaxis. ⋯ After a median follow-up of 18.2 months (range: 6.3-52.1), 18 patients remained alive (53%). Four patients died without recurrence/progression of underlying diseases giving a TRM of 13% (95% CI, 5%-33%). HCT from an HLA-mismatched family member is feasible without ex vivo T cell depletion when reduced-intensity conditioning containing anti-hymocyte globulin is performed.
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Biol. Blood Marrow Transplant. · Jan 2009
Study of kidney function impairment after reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation. A single-center experience.
Acute renal failure (ARF) is a life-threatening complication after allogeneic stem cell transplantation (Allo-HSCT). Identification of ARF risk factors could be useful to develop preventive strategies for patients at high risk. The goal of this study was to evaluate the incidence and risk factors of ARF after reduced intensity conditioning Allo-HSCT (Allo-RIC). ⋯ Patients who experienced ARF had lower 1-year overall survival (OS; 53% versus 74%, P < .05). ARF is a frequent complication in patients after Allo-RIC, and it has a negative impact on outcome. Identification of ARF risk factors could help to avoid exposure to nephrotoxic drugs during the follow-up in patients at high risk.
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Biol. Blood Marrow Transplant. · Jan 2009
Graft-versus-host disease prophylaxis with everolimus and tacrolimus is associated with a high incidence of sinusoidal obstruction syndrome and microangiopathy: results of the EVTAC trial.
A calcineurin inhibitor combined with methotrexate is the standard prophylaxis for graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Everolimus, a derivative of sirolimus, seems to mediate antileukemia effects. We report on a combination of everolimus and tacrolimus in 24 patients (median age, 62 years) with either myelodysplastic syndrome (MDS; n = 17) or acute myeloid leukemia (AML; n = 7) undergoing intensive conditioning followed by HSCT from related (n = 4) or unrelated (n = 20) donors. ⋯ The study was terminated prematurely because an additional 6 patients (25%) developed sinusoidal obstruction syndrome (SOS), which was fatal in 2 cases. With a median follow-up of 26 months, the 2-year overall survival rate was 47%. Although this new combination appears to be effective as a prophylactic regimen for acute GVHD, the incidence of TMA and SOS is considerably higher than seen with other regimens.