AMD3100 (A), an inhibitor of SDF-1∞ binding to CXCR4, has been used alone and with G-CSF (G) to mobilize CD34+ cells from healthy volunteers and donors and from cancer patients undergoing autologous ...transplantation. In several studies it enhanced mobilization of poor mobilizers. Therefore, a CUP was submitted to the FDA; more than 100 patients (most commonly NHL; N=42) have been entered. Results from the first 70 patients enrolled are reported here. Three patients underwent a second mobilization with A following initial failure (2) and disease relapse (1); data on the first mobilization is in this report. Entry requirements include documented inability to mobilize 2 x 106 CD34+ cells/kg. Patients must have acceptable cardiac and pulmonary status, no active infection, and to have WBC >3.0 x 109/L, ANC > 1.5 x109/L, PLT >100,000 x 109/L, LFT within 2 x ULN, and creatinine clearance >60 ml/min. as well as other acceptable laboratory values. After signing consent and undergoing history, physical, laboratory, CXR, and ECG evaluation, patients are given G (10 mg/kg) for 4 days. At about 10 p.m. on day 4 they receive 240 mg/kg of A subcutaneously. The next a.m. they receive G and undergo apheresis. The evening A, the a.m. G, and the apheresis are repeated until enough cells are collected or until it is clear insufficient cells could be collected. There were 38 males and 32 females. Five were 18 years or younger (10, 12, 13, 16 and 18 years). The rest ranged in age from 21 to 81 years. Most common diseases were NHL (31), MM (14), AML (8), and Hodgkin's disease (HD) (10). The 70 patients had undergone 93 possible mobilizations and 16 patients failed multiple prior regimens. Nearly all (91/93) prior mobilization regimens contained G. The most common regimens were G alone (33), cyclophosphamide plus G (17), and cyclophosphamide plus G plus other agents (30). In a subset of patients (N=27) the median time between the prior failed mobilization and the CUP mobilization was 34 days. A was generally well tolerated with AEs being similar to that previously reported. Only one SAE was felt related - patient with worsening of GI symptoms. The percent of patients collecting >2 x 106 cells/kg for the more common cancers were 58 for NHL, 64 for MM, 50 for AML, and 70 for HD. For those collecting >2 x 106 cells/kg (N=40) the median collection was 4.72 106 cells/kg in a median of 3.5 aphereses. The number of these patients transplanted was 36 of 40 with 31 successful engraftments, 3 pending, and two deaths post successful PMN, but not PLT engraftment. Of all the patients transplanted 4 additional patients have died. Durability has been good with at least 24 patients at 6 months or beyond. The success of mobilization compares very favorably with prior published data. A offers a generally safe and effective way to enhance mobilization of patients who have previously failed mobilizations.
•Outpatient transplantation for myeloma is safe and feasible.•The HCT-CI did not have significant effect on survival for this study cohort.•Poor performance status appeared to be associated with ...lower survival.•Patients with KPS and comorbidities are at a risk for unplanned admissions.
Although outpatient autologous stem cell transplantation (ASCT) is safe and feasible in most instances, some patients undergoing planned outpatient transplantation for multiple myeloma (MM) will need inpatient admission for transplantation-related complications. We aim to evaluate the difference, if any, between outpatient and inpatient ASCT cohorts of MM patients in terms of admission rate, transplantation outcome, and overall survival. We also plan to assess whether the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) and Karnofsky Performance Status (KPS) can predict unplanned admissions after adjusting for confounding factors. Patients with MM (n = 448) who underwent transplantation at our institution between 2009 and 2014 were included in this retrospective analysis. Patients were grouped into 3 cohorts: cohort A, planned inpatient ASCT (n = 216); cohort B, unplanned inpatient admissions (n = 57); and cohort C, planned outpatient SCT (n = 175). The statistical approach included descriptive, bivariate, and survival analyses. There were no differences among the 3 cohorts in terms of type of myeloma, stage at diagnosis, time from diagnosis to transplantation, CD34 cell dose, engraftment kinetics, and 100-day response rates. Serum creatinine was higher and patients were relatively older in both the planned inpatient (median age, 62 years; range, 33 to 80 years) and unplanned (median age, 59 years; range, 44 to 69 years) admission cohorts compared with the outpatient-only cohort (median age, 57 years; range, 40 to 70 years) (P < .05). Performance status (cohort A: median, 90%; range, 60% to 100%; cohort B: 80%, 50% to 100%; cohort C: 80%, 60% to 100%) was lower (P < .05) and HCT-CI score (cohort A: median, 1.78; range, 0 to 8; cohort B: 2.67, 0 to 9; cohort C: 2.16, 0 to 7) was higher (P < .004) in both inpatient groups compared with the planned outpatient cohort. With a median follow up of 5 years, poor performance status (KPS <70%) appeared to be associated with worse survival (P < .002). HCT-CI >2 also appeared to be associated with worse outcomes compared with HCT-CI 0 to 1, the the difference did not reach statistical significance (hazard ratio, 1.41l 95% confidence interval, 0.72 to 2.76). Only 1 patient out of 448 died from a transplantation-related cause. Outpatient transplantation for myeloma is safe and feasible. In our experience, one-third of the patients undergoing outpatient transplantation needed to be admitted for transplantation-related toxicities. Patients in this group had lower preexisting KPS and higher HCT-CI scores. Whether planned admission for this group would have prevented unplanned admissions and undue stress on patients and the healthcare system should be tested in a prospective manner.
Highlights • Contemporary data on outcomes of allogeneic hematopoietic cell transplant (HCT) for T-cell acute lymphoblastic leukemia (T-ALL) are limited. • Overall survival after HCT at 5 years for ...T- ALL was 34%. The corresponding cumulative incidence of non-relapse mortality and relapse was 26% and 41% respectively. • In multivariable analysis, factors significantly associated with overall survival were the use of TBI (HR 0.57, P=0.02); age >35 (HR 1.55, P=0.025), and relapsed/refractory disease status at transplantation (HR 1.98, P=0.005). • Allogeneic HCT remains a potentially curative option in selected patients with T-ALL, however relapse remains the major cause of treatment failure.
AGVHD is a major cause of morbidity and mortality after allogeneic stem cell transplantation (SCT). Primary treatment of aGVHD with corticosteroids achieves a complete response (CR) rate of 20–40%. ...Mesenchymal stem cells (MSC) derived from adult bone marrow have immunomodulatory effects. Preclinical and clinical data suggest that MSC inhibit T-cell alloreactivity. Thus, we initiated a trial to investigate the use of Prochymal, ex-vivo cultured adult human MSC derived from unrelated donors, added to conventional steroid therapy for the primary treatment of aGVHD.
Patients (pts) and Methods: Pts must have had newly clinically diagnosed aGVHD, grades II-IV using standard grading criteria, after undergoing a related or unrelated allogeneic SCT, or donor lymphocyte infusion (DLI). Endpoints of the study included safety of administration of Prochymal and response rates of aGVHD by day 28 after Prochymal infusion. Treatment with steroids (2mg/kg) and Prochymal, randomized to 2 (low) or 8 million (high) cells/kg, was initiated at the time of GVHD diagnosis. Pts were kept at therapeutic levels of tacrolimus, cyclosporine, or MMF for GVHD prophylaxis. 2 doses of Prochymal were given 3–5 days apart, with the first given within 72 hrs of steroid initiation. Corticosteroids were maintained at 2 mg/kg for at least 1 week. Pts were monitored for response and toxicity weekly for 4 weeks, and then followed for safety on a 2 year long-term follow-up study.
Results: 32 pts were enrolled with interim data available for 30 pts (21 males, 9 females) with median age 52 (range 34–67). AGVHD developed following matched sibling (n=15), matched unrelated (n=11), or DLI (n=4) infusions. Overall aGVHD was noted to be grade II (n=20), grade III (n=7), and grade IV (n=3), and involved GI (n=13), skin (n=11), GI and skin (n=4), and GI and liver (n=2). Prochymal dose was low in 17 pts and high in 13 pts. All pts received both Prochymal infusions. 26 of 29 evaluable pts (90%) initially responded to treatment of their aGVHD: 19 achieved CR with no evidence for GVHD, and 7 achieved PR as documented by a reduction in 1 organ stage. Nine pts (31%) eventually required a second line agent to control aGVHD. No infusional toxicities were noted. One pt developed atrial fibrillation 1 day following the second Prochymal infusion. No unexpected ectopic tissue formation was noted in any pt by CT scans at day 28. Currently, 8 pts have died from progression of aGVHD (n=2), intracranial bleed following fall (n=1), relapse (n=1), and infection (n=4) at a median of 44 days (range 13–58) following Prochymal infusion.
Conclusions: The addition of Prochymal to corticosteroids resulted in a high response rate with minimal added toxicity when used for the primary treatment of aGVHD, and suggests that MSC have unique biological properties that may be effective for treatment of GVHD. Longer follow-up is necessary to determine if Prochymal has any impact on survival. Phase III studies are warranted, including studies in steroid refractory GVHD.
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