Weight-based dosing of intravenous busulfan is widely used in hematopoietic cell transplantation. However, a variety of dosing weights have been described. The objective of this retrospective study was to determine the pharmacokinetic impact of using ideal body weight as the initial dosing weight in obese as compared to non-obese transplant recipients. The secondary objectives were to describe the use of alternative dosing weights, the impact on survival, and the rates of toxicities. The mean steady-state concentration was 779.3 ng/mL (n = 82) in the non-obese cohort and 673.7 ng/mL (n = 63) in the obese cohort (p < 0.001). A smaller proportion of concentrations were below goal in the non-obese cohort (10% vs. 41%, p < 0.001). Ideal body weight and adjusted body weights with a 25 and 40% correction factor are appropriate in nonobese patients; adjusted body weights with a 25 and 40% correction factor are appropriate in obese patients. There was no difference in overall survival (p = 0.18); there was a difference in median progression-free survival (1078 vs. 500 days, p = 0.045) in the non-obese compared to obese cohorts. The use of ideal body weight to dose busulfan resulted in lower steady-state concentrations, a larger proportion of subtherapeutic concentrations, and worse progression-free survival in obese patients.

Graft-versus-host-disease (GVHD) is a life threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT). The calcineurin inhibitor tacrolimus is commonly used in combination with other immunosuppressants to prevent GVHD; however the optimal serum target concentration for tacrolimus in this population remains unknown. A retrospective review was conducted to determine whether an association exists between tacrolimus concentrations and transplant-related outcomes, specifically acute GVHD, as well as the rate of renal toxicity and mortality. Data from 203 patients who underwent an allogeneic HSCT from a related (n=95) or unrelated (n=108) donor between January 1, 2003 and December 31, 2011 at a large academic hospital was analyzed. Sixty-two (31%) patients developed acute GVHD within the first 30 days following allogeneic stem cell transplant. Median tacrolimus concentrations at day 0, 7, 14, and 28 were 11.2, 13.8, 13.5 and 10.2 ng/mL, respectively among those who developed acute GVHD. Patients who did not develop acute GVHD had similar tacrolimus concentrations of 10.4, 13.1, 12.3 and 9.9 ng/mL for the same respective time points. Serum tacrolimus concentrations were similar across all grades of GVHD and there was no correlation between drug concentrations with respect to renal toxicity. Patients who developed renal dysfunction (n=18) had tacrolimus concentrations similar to the median concentration of the entire cohort, including those who did not experience renal toxicity. Overall mortality among the 203 included patients was 49%. Mortality was higher among patients who developed acute GVHD (55%) than in patients who did not experience the disease (47%). The results of this analysis support previous conclusions that tacrolimus blood concentrations are not associated with acute GVHD within the first 30 days post allogeneic HSCT.

In this prospective phase II clinical trial, multiple myeloma (MM) patients were randomized to receive a second (tandem) autologous stem cell transplantation (ASCT) based on whether they achieved a partial response or worse (≤PR) following initial ASCT (ASCT1). Patients who achieved a very good partial response or better (≥VGPR) had salvage ASCT at relapse. Seventy-five patients received conditioning therapy and ASCT1. A total of 44 patients (59%) achieved ≥VGPR, whereas 31 patients entered ≤PR and were offered tandem ASCT. In all, 20 patients agreed to tandem ASCT. Demographic and clinical characteristics were similar between the two cohorts except for median lactate dehydrogenase (LDH) ( P = 0.0141) and percentage of marrow plasma cells before ASCT1 ( P = 0.0047), both lower in the ≥VGPR group. Intent to treat analysis showed that patients who achieved ≥VGPR to ASCT1 had a trend toward improved progression-free survival (PFS) (37 vs. 26 months, P = 0.078) and superior overall survival (OS) (not reached vs. 50 months, P = 0.0073). Patients with ≤PR who declined tandem transplantation had shortened PFS (20 vs. 28 months, P = 0.05) but similar OS (53 vs. 57.5 months, P = 0.29) compared to those who received it. Thus, a favorable clinical response to ASCT1 identifies a low-risk group with superior long-term prognosis despite similar PFS.

Abstract The role of tandem transplants as well as a later salvage second transplant has been in the center of interest for many myeloma investigators. Also, the need for tandem ASCT in patients (pts) achieving very good partial remission (VGPR) or complete remission has not been studied prospectively. We conducted a prospective phase II clinical trial in which enrolled myeloma pts are assessed after the first ASCT and offered either 2nd tandem ASCT if they achieve ≤ PR or maintenance if they achieve ≤ VGPR. These latter pts received 2nd salvage transplant after relapse. The conditioning regimens used were different for the two ASCT: Busulfan 0.75 mg/kg PO q 6 hr days –8 through –5, Cyclophosphamide (CP) 60 mg/kg IV days –3 and –2, and Etoposide 10 mg/kg IV days –4 to –2 for the first ASCT, and 96 hr (days –6 to –3) continuous IV CP 6 gr/m2 and total body irradiation (TBI) 600 cGy (days –2 and –1) for the second ASCT. Etoposide was omitted if pts were ≤ 65 year old, and TBI was substituted by melphalan 140 mg/m2 if prior radiation did not allow TBI. Between the years 2001-2009, 76 pts were enrolled. Of the 31 pts planned to have tandem ASCT, 20 received tandem ASCT, 2 additional pts had tandem auto-allo transplants and one patient had progressive disease. The primary reasons for not receiving the planned tandem ASCT were lack of socioeconomic resources and physical co-morbidities. Maintenance treatment was offered to both groups of pts. There were no treatment related mortalities in the ASCT pts. We compared the progression-free (PFS) and overall (OS) survival following the first ASCT between pts who received tandem ASCT (n=20) and pts who received single ASCT (n=54). The median PFS for tandem pts was 27 mo (range, 10-93) versus 28 mo for single ASCT (range, 4-99) (P=0.889); the OS was 38 mo (range, 11-120) versus 72 mo (range, 5-136), respectively (P=0.293). At the present time, a total of 7 (35%) and 30 (55%) pts are still alive in the tandem and single ASCT groups, respectively. Among the tandem pts, 2 underwent salvage ASCT and one non-myeloablative allogeneic transplant (allo-SCT); while in the single ASCT group 6 had salvage ASCT and 6 had allo-SCT. All salvage transplants were done at a median of 37 mo (range, 8-91) from 1st ASCT. In conclusion, pts who achieve ≤ VGPR after 1st ASCT have similar PFS and may be better OS than pts who had tandem ASCT. Thus, the use of such response criteria may identify a group of lower risk pts that will do well without the upfront tandem ASCT. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4618. doi:1538-7445.AM2012-4618

The National Marrow Donor Program, in partnership with the American Society for Blood and Marrow Transplantation, sponsored and organized a series of symposia to identify complex issues affecting the delivery of hematopoietic cell transplantation (HCT) and to collaboratively develop options for solutions. “Hematopoietic Cell Transplantation in 2020: A System Capacity Initiative” used a deliberative process model to engage professional organizations, experts, transplant centers, and stakeholders in a national collaborative effort. Year 2 efforts emphasized data analysis and identification of innovative ideas to increase HCT system efficiency, address future capacity requirements, and ensure adequate reimbursement for HCT programs to meet the projected need for HCT. This report highlights the deliberations and recommendations of Year 2 and the associated symposium held in September 2011.

BACKGROUND: Granulocyte–colony‐stimulating factor (G‐CSF)‐mobilized peripheral blood progenitor cells (PBPCs) are the most common source of cells used for hematopoietic transplantation. Benign ethnic neutropenia has been found in persons of African descent, affecting circulating white blood cells (WBCs), but not WBC production within marrow. Persons of African descent have reduced neutrophil mobilization after steroid administration, and newborns have fewer nucleated and progenitor cells in their cord blood.STUDY DESIGN AND METHODS: Twenty‐two African American (AA) and 12 Hispanic PBPC donors were age, sex, and weight matched with 34 Caucasian donors. Groups were compared based on WBC and neutrophil counts after mobilization and numbers of CD34+ cells collected on Day 5 of G‐CSF mobilization.RESULTS: AA donors had significantly lower baseline WBC (6.1 ± 1.1 vs. 7.1 ± 1.7, p = 0.04) and neutrophil (3.4 ± 1.1 vs. 4.5 ± 1.3, p = 0.01) counts compared to matched Caucasian donors. G‐CSF–stimulated AAs had a significantly greater increase in WBC and neutrophil counts compared to matched Caucasians (889 ± 293% vs. 665 ± 230% neutrophils, p = 0.02). There was no significant difference in product cell counts when comparing total nucleated, CD3+, CD34+, and mononuclear cells or colony‐forming units (CFUs) between Caucasians and Hispanics or AAs and trends to greater numbers of neutrophils in products from AA donors.CONCLUSION: When stimulated by G‐CSF, AAs are able to increase WBC and neutrophil counts to a higher degree than Caucasians, achieving similar numbers of neutrophil and progenitor cells in apheresis products despite starting from lower baseline blood counts.

Disease remission in patients with myelodysplastic syndromes can be achieved with azanucleosides, which act as pyrimidine analogs and hypomethylating agents. However, despite treatment with azanucleoside induction, patients with myelodysplastic syndromes nearly always relapse. Allogeneic hematopoietic cell transplantation (HCT) can be curative, but it is risky. Given that azanucleosides affect human leukocyte antigen expression and lymphocyte reactivity, we conducted a retrospective study to define the impact of pre-HCT azanucleoside therapy on post-HCT donor chimerism. Patients receiving azanucleoside induction therapy achieved rapid and high levels of donor chimerism post-transplant. Lineage analysis also found rapid donor chimerism of lymphocyte and granulocyte subsets. These data indicate the feasibility of pretransplant azanucleoside therapy in patients who subsequently receive an HCT.