Edmund K. Waller

Acute toxicities of unrelated bone marrow versus peripheral blood stem cell donation: results of a prospective trial from the NMDP

Although peripheral blood stem cells (PBSCs) have replaced bone marrow (BM) as the most common unrelated donor progenitor cell product collected, a direct comparison of concurrent PBSC versus BM donation experiences has not been performed. We report a prospective study of 2726 BM and 6768 PBSC donors who underwent collection from 2004 to 2009. Pain and toxicities were assessed at baseline, during G-CSF administration, on the day of collection, within 48 hours of donation, and weekly until full recovery. Peak levels of pain and toxicities did not differ between the 2 donation processes for most donors. Among obese donors, PBSC donors were at increased risk of grade 2 to 4 pain as well as grade 2 to 4 toxicities during the pericollection period. In contrast, BM donors were more likely to experience grade 2 to 4 toxicities at 1 week and pain at 1 week and 1 month after the procedure. BM donors experienced slower recovery, with 3% still not fully recovered at 24 weeks, whereas 100% of PBSC donors had recovered. Other factors associated with toxicity included obesity, increasing age, and female sex. In summary, this study provides extensive detail regarding individualized risk patterns of PBSC versus BM donation toxicity, suggesting donor profiles that can be targeted with interventions to minimize toxicity.

Allogeneic hematopoietic cell transplantation for chemotherapy-unresponsive mantle cell lymphoma: a cohort analysis from the center for international blood and marrow transplant research.

Patients with chemorefractory mantle cell lymphoma (MCL) have a poor prognosis. We used the Center for International Blood and Marrow Transplant Research database to study the outcome of 202 patients with refractory MCL who underwent allogeneic hematopoietic cell transplantation (allo-HCT) using either myeloablative (MA) or reduced-intensity/nonmyeloablative conditioning (RIC/NST), during 1998-2010. We analyzed nonrelapse mortality (NRM), progression/relapse, progression-free survival (PFS), and overall survival (OS). Seventy-four patients (median age, 54 years) received MA, and 128 patients (median age, 59 years) received RIC/NST. Median follow-up after allo-HCT was 35 months in the MA group and 43 months in the RIC/NST group. At 3 years post-transplantation, no significant between-group differences were seen in terms of NRM (47% in MA versus 43% in RIC/NST; Pxa0= .68), relapse/progression (33% versus 32%; Pxa0= .89), PFS (20% versus 25%; Pxa0= .53), or OS (25% versus 30%; Pxa0= .45). Multivariate analysis also revealed no significant between-group differences in NRM, relapse, PFS, or OS; however, receipt of a bone marrow or T cell-depleted allograft was associated with an increased risk of NRM and inferior PFS and OS. Our data suggest that despite a refractory disease state, approximately 25% of patients with MCL can attain durable remission after allo-HCT, and conditioning regimen intensity does not influence outcome of allo-HCT.

Impact of pretransplantation conditioning regimens on outcomes of allogeneic transplantation for chemotherapy-unresponsive diffuse large b cell lymphoma and grade iii follicular lymphoma

Patients with chemorefractory non-Hodgkin lymphomas generally have a poor prognosis. We used the observational database of the Center for International Blood and Marrow Transplant Research to study the outcome of 533 patients with refractory diffuse large B cell lymphoma (DLBCL) or grade III follicular lymphoma (FL-III) who underwent allogeneic hematopoietic cell transplantation (allo-HCT) using either myeloablative (MA; nxa0=xa0307) or reduced-intensity/nonmyeloablative conditioning (RIC/NST; nxa0=xa0226) between 1998 and 2010. We analyzed nonrelapse mortality (NRM), relapse/progression, progression-free survival (PFS), and overall survival (OS). Only 45% of the patients at transplantation had a Karnofsky performance score of ≥90%. Median follow-up of surviving patients after MA and RIC/NST allo-HCT is 35 months and 30 months, respectively. At 3 years, MA allo-HCT was associated with a higher NRM compared with RIC/NST (53% versus 42%; Pxa0=xa0.03), similar PFS (19% versus 23%; Pxa0=xa0.40), and lower OS (19% versus 28%; Pxa0=xa0.02), respectively. On multivariate analysis, FL-III histology was associated with lower NRM (relative risk [RR],xa0.52), reduced risk of relapse/progression (RR,xa0.42), and superior PFS (RR,xa0.51) and OS (RR,xa0.53), whereas MA conditioning was associated with reduced risk of relapse/progression (RR,xa0.66). Despite a refractory state, a small subset of DLBCL and FL-III patients can attain durable remissions after allo-HCT. Conditioning regimen intensity was not associated with PFS and OS despite a higher risk of relapse/progression with RIC/NST allo-HCT.

Providing Personalized Prognostic Information for Adult Leukemia Survivors

Prediction of subsequent leukemia-free survival (LFS) and chronic graft-versus-host disease (GVHD) in adults with acute leukemia who survived at least 1 year after allogeneic hematopoietic cell transplantation is difficult. We analyzed 3339 patients with acute myeloid leukemia and 1434 patients with acute lymphoblastic leukemia who received myeloablative conditioning and related or unrelated stem cells from 1990 to 2005. Most clinical factors predictive of LFS in 1-year survivors were no longer significant after 2 or more years. For acute myeloid leukemia, only disease status (beyond first complete remission) remained a significant adverse risk factor for LFS 2 or more years after transplantation. For lymphoblastic leukemia, only extensive chronic GVHD remained a significant adverse predictor of LFS in the second and subsequent years. For patients surviving for 1 year without disease relapse or extensive chronic GVHD, the risk of developing extensive chronic GVHD in the next year was 4% if no risk factors were present and higher if noncyclosporine-based GVHD prophylaxis, an HLA-mismatched donor, or peripheral blood stem cells were used. Estimates for subsequent LFS and extensive chronic GVHD can be derived for individual patients or populations using an online calculator (http://www.cibmtr.org/LeukemiaCalculators). This prognostic information is more relevant for survivors than estimates provided before transplantation.

Plerixafor in combination with granulocyte-colony-stimulating factor after chemotherapy increases mobilization efficiency in patients with lymphoma or myeloma: results of a Phase II clinical trial.

We tested whether adding plerixafor to G‐CSF mobilization after chemotherapy would increase the proportion of patients collecting the target number of CD34+ cells/kg in 1 day of apheresis to >75%.

Monitoring Blood for CD34+ Cells to Determine Timing of Hematopoietic Progenitor Cells Apheresis

Hematopoietic Progenitor Cell (HPC) Apheresis generally results in a mononuclear cell product that is highly enriched for hematopoietic stem and progenitor cells when performed on autologous patients in whom autologous stem cell transplant is planned who have been mobilized with cytotoxic chemotherapy and exogenous hematopoietic growth factors (cytokines) and possibly CXCR4 antagonists. Alternatively, patients scheduled for autologous transplants may be mobilized with cytokines only or a combination of cytokines and CXCR4 antagonists. Allogeneic Donors, either matched related donors (MRD) or matched unrelated donors (MUD), are typically mobilized with cytokines only. The HPC Apheresis product, enriched for hematopoietic progenitor cells collected from the patient/donors peripheral blood via an apheresis system, is used for restoring hematopoiesis in the patient/recipient who has received myeloablative therapy. Timing of the collection of an HPC Apheresis product from allogeneic donors is based on the schedule of the recipients myeloablative regime. However, the optimal timing of collection on HPC Apheresis product from a patient scheduled for an autologous stem cell transplant can be complex.

Hematopoietic Progenitor Cell Apheresis Processing

Modern apheresis generally results in a mononuclear cell product that is highly enriched for hematopoietic stem and progenitor cells when performed on patients who have mobilized with myeloid growth factors, CXCR4 antagonists or upon recovery from cytotoxic chemotherapy. The duration of apheresis during the days in which elevated numbers of CD34 positive cells are present in the blood depends upon the efficiency of the apheresis maneuver, the numbers of the CD34 target cell population in the blood, and the weight of the intended transplant recipient. The ability to freeze a hematopoietic progenitor cell (HPC) graft and subsequently thaw it while retaining viability of the hematopoietic stem and progenitor cell population has permitted routine collection of autologous hematopoietic progenitor cell grafts for treatment of patients with cancer using myeloablative doses of chemotherapy and radiation with stem cell support.