[Show abstract][Hide abstract] ABSTRACT: Recent studies support the use of bortezomib-based therapies in light chain amyloidosis (AL). We performed a retrospective analysis of the safety, efficacy and long-term survival (median follow-up 3 years) after bortezomib-based treatment in 28 consecutive patients with de novo AL deemed ineligible at initial presentation. The first 14 patients received bortezomib and dexamethasone (VD), and the second 14 patients received cyclophosphamide, bortezomib and dexamethasone (CVD; CyBorD). Both regimens were well tolerated with no treatment-related mortality. The overall hematological response (HR) rate was 93% in both the groups. Median time to response was shorter in the CVD group (39 days vs 96 days in the VD group; P=0.002). Hematological and organ responses induced with bortezomib-based therapy enabled 8 (33%) of initially transplant ineligible patients to undergo autologous hematopoietic stem cell transplantation (AHCT), including 4 patients with cardiac stage III or IV. Seven of the eight patients (88%) who underwent subsequent AHCT achieved sustained HR at a median of 33 months posttransplant. These data suggest that bortezomib-based induction followed by AHCT is a viable therapeutic strategy for transplant-ineligible AL. Larger, multicenter prospective trials are necessary to confirm our findings.Bone Marrow Transplantation advance online publication, 27 April 2015; doi:10.1038/bmt.2015.73.
Bone marrow transplantation 04/2015; 50(7). DOI:10.1038/bmt.2015.73 · 3.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Clinical outcomes after primary graft failure (PGF) remain poor. Here we present a large retrospective analysis (n=23 272) which investigates means to prevent PGF and early detection of patients at high risk. In patients with hematologic malignancies, who underwent their first myeloablative allogeneic hematopoietic cell transplantation, PGF was reported in 1,278 (5.5%), and there was a marked difference in PGFs using peripheral blood stem cell compared to bone marrow grafts (2.5 vs 7.3%; P<0.001). A 4-fold increase of PGF was observed in myeloproliferative disorders compared to acute leukemia (P<0.001). Other risk factors for PGF included recipient age below 30, HLA-mismatch, male recipients of female donor grafts, ABO-incompatibility, busulfan/cyclophosphamide conditioning, and cryopreservation. In bone marrow transplants, total nucleated cell doses ⩽2.4 × 10(8)/kg were associated with PGF (OR 1.39; P<0.001). The use of tacrolimus-based immunosuppression and granulocyte colony-stimulating factor were associated with decreased PGF risk. These data, allow clinicians to do more informed choices with respect to graft source, donor selection, conditioning and immunosuppressive regimens to reduce the risk of PGF. Moreover, a novel risk score determined on day 21 post-transplant may provide the rationale for an early request for additional hematopoietic stem cells.Leukemia accepted article preview online, 16 March 2015. doi:10.1038/leu.2015.75.
[Show abstract][Hide abstract] ABSTRACT: Overall survival following hematopoietic cell transplantation (HCT) has improved over the past two decades through better patient selection and advances in HLA typing, supportive care, and infection prophylaxis. Nonetheless, mortality rates are still unsatisfactory and transplant-related mortality remains a major cause of death after unrelated allogeneic HCT. Since there are no known pre-HCT, non-HLA biologic predictors of survival following transplant, for over a decade, scientists have been investigating the role of non-HLA germline genetic variation in survival and treatment-related mortality after HCT. Variation in single nucleotide polymorphisms (SNPs) has the potential to impact chemotherapy, radiation, and immune responses, leading to different post-HCT survival outcomes. In this paper, we address the current knowledge of the contribution of genetic variation to survival following HCT and discuss study design and methodology for investigating HCT survival on a genomic scale.
[Show abstract][Hide abstract] ABSTRACT: Hematopoietic cell transplantation (HCT) with non-myeloablative (NMA) conditioning for lymphoproliferative diseases (LD) includes fludarabine with and without low-dose TBI. Transplant outcomes were compared among patients aged ⩾40 years with LD who received a HCT with TBI (N=382) or no-TBI (N=515) NMA from 2001 to 2011. The groups were comparable except for donor, graft, prophylaxis for GVHD, disease status and year of HCT. Cumulative incidences of grades II-IV GVHD at 100 days were 29% and 20% (P=0.001) and of chronic GVHD at 1 year were 54% and 44% (P=0.004) for TBI and no-TBI, respectively. Multivariate analysis of progression/relapse, treatment failure and mortality showed no outcome differences by conditioning. Full donor chimerism at day 100 was observed in 82% vs 64% in the TBI and no-TBI groups, respectively (P=0.006). Subsets of the four most common conditioning/GVHD prophylaxis combinations demonstrated higher rates of grades II-IV acute (P<0.001) and chronic GVHD (P<0.001) among recipients of TBI-mycophenolate mofetil (MMF) compared with other combinations. TBI-based NMA conditioning induces faster full donor chimerism, but overall survival outcomes are comparable to no-TBI regimens. Combinations of TBI and MMF are associated with higher rates of GVHD without impact on survival outcomes in patients with LD.Bone Marrow Transplantation advance online publication, 1 December 2014; doi:10.1038/bmt.2014.269.
Bone Marrow Transplantation 12/2014; 50(3). DOI:10.1038/bmt.2014.269 · 3.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cytokine-based mobilization in light chain (AL ) amyloidosis is frequently complicated by fluid overload, weight gain, cardiac arrhythmias, and peri-mobilization mortality. We analyzed hematopoietic progenitor cells (HPC) mobilization outcomes in 49 consecutive AL amyloidosis patients at our institution between 2004-2013 with G-CSF (G) (10μg/kg/d) (n=25) vs. an institutional protocol to limit G exposure using plerixafor (P) (P at 0.24mg/kg SC starting day 3 of G 10μg/kg) (n=24). G+P strategy yielded higher total CD34+ cells/kg (12.8 ×106 vs. 6.3 ×106; p<0.001), and CD34+ cells/kg collected on day 1(10.8 ×106 vs. 4.9 ×106, p=0.004) compared with the G cohort. More G+P patients collected ≥5 ×106 CD34+HPCs/kg (22 vs.16, p=0.02) and ≥10 ×106 CD34+ HPCs/kg (13 vs. 5,p=0.01). Four patients (16%) had mobilization failure with G; none with G+P. Peri-mobilization weight gain was lower with G+P strategy (median weight gain 1 vs. 7 lbs., p=0.009). Numbers of apheresis sessions (median 1 vs. 1, p=0.52), number of hospitalization days (median 1.1 vs. 1.6, p=0.52), transfusions, use of intravenous antibiotics and cardiac arrhythmias were similar. In conclusion our study demonstrates that upfront use of G+P as a mobilization strategy results in superior HPC collection, no mobilization failures, and less weight gain than G alone.
Biology of Blood and Marrow Transplantation 12/2014; 20(12). DOI:10.1016/j.bbmt.2014.08.002 · 3.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Blood and Marrow Transplant Clinical Trials Network conducts large, multi-institutional clinical trials with the goal of improving the outcomes of hematopoietic cell transplantation (HCT) for patients with life-threatening disorders. Well designed HCT trials benefit from standardized criteria for defining diagnoses, treatment plans and graft source selection. In this perspective, we summarize evidence supporting criteria for the selection of related and unrelated adult volunteer progenitor cell donors or umbilical cord blood units. These standardized criteria for graft source selection have been adopted by the BMT CTN to enhance the interpretation of clinical findings within and among future clinical protocols.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 09/2014; 21(1). DOI:10.1016/j.bbmt.2014.09.017 · 3.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hematopoietic cell transplantation (HCT) is a complex and highly specialized medical treatment that is associated with significant risks, including death. Furthermore, transplantation is offered to patients who often have no other curative treatment alternatives. The routine-consent process for HCT typically occurs before HCT and is influenced by many factors related to patients, physicians and the transplant per se. These factors can impede the consent process and subsequently result in a failure of proper engagement in and an understanding of the procedure with resultant adverse consequences influencing patients and even the patient-physician relationship. We contend that informed consent is a dynamic and ongoing process and that better patient education can assist in the decision making, fulfill the ethical principle of respect for autonomy and engage the patient to maximize compliance and adherence to therapy. This manuscript reviews the key literature pertaining to the decision-making and consent process in HCT and proposes guidelines for improving the consent process. Strategies for improving patient comprehension, engagement and enhancing consent forms are discussed.Bone Marrow Transplantation advance online publication, 22 September 2014; doi:10.1038/bmt.2014.207.
Bone Marrow Transplantation 09/2014; 50(1). DOI:10.1038/bmt.2014.207 · 3.47 Impact Factor