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Haploidentical transplantation using G-CSF-mobilized T-cell replete PBSCs and post-transplantation CY after non-myeloablative conditioning is safe and is associated with favorable outcomes

Bone Marrow Transplantation volume 49, pages 1124–1126 (2014)Cite this article

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The availability of HLA-matched donors remains a major obstacle for successful allogeneic hematopoietic cell transplantation (HSCT). Near universal donor availability and shorter donor search times make haploidentical HSCT (haplo-HSCT) a very attractive transplant option in patients who otherwise lack an HLA-matched donor. Using high-dose CY in the early post-transplant period (PT-CY), Luznik et al.1 from Johns Hopkins University developed a novel haplo-HSCT regimen that significantly improved the outcomes and has eliminated the need for expensive and labor-intensive ex vivo T-cell depletion.1 Their initial approach using non-myeloablative (NMA) conditioning and BM as the graft source was associated with low rates of GVHD and NRM but was somewhat limited by relatively high relapse rates.1 Recently, several groups have reported encouraging outcomes using PBSC and more intensive myeloablative conditioning regimens on this PT-CY haplo-HSCT platform.2, 3, 4, 5 We hypothesized that relatively high T-cell numbers in the G-CSF-mobilized PBSC graft would help in engraftment and reduce relapse rates without the need to increase the intensity of the conditioning regimen on this PT-CY haplo-HSCT platform. After an approval from our institutional review board, we retrospectively analyzed all the patients treated on this haplo-HSCT regimen since July 2009. For this protocol NMA conditioning regimen, GVHD prophylaxis, growth factor support and antimicrobial prophylaxis were adopted from the initial report by Luznik et al.1 G-CSF-mobilized PBSCs from related haploidentical donors were used as a graft source. Patients were monitored weekly for CMV reactivation through quantitative PCR of blood and were treated pre-emptively for CMV viremia (>500 DNA copies/mL) with IV ganciclovir or oral valganciclovir for 14 days. Acute GVHD was graded according to the Glucksberg Criteria.6 Chronic GVHD was diagnosed as per the NIH criteria and graded as limited or extensive according to the standard guidelines.7 Patients were grouped into CR or active disease based on the disease status derived from antecedent BM performed within 30 days before transplantation. Patients with persistent cytogenetic abnormalities even at low level on BM biopsy were considered to have persistent disease. Donor–recipient chimerism analysis in the post-transplantation period was performed using PCR analysis of single tandem repeats from BM on day 30, day 100 and then every 3 months from the peripheral blood for 1 year. Donor engraftment was defined as ⩽5% recipient cells and graft failure as ⩽5% donor cells on BM single tandem repeats any time after transplantation not secondary to progressive hematologic malignancy. Probabilities of OS and RFS were estimated using the Kaplan–Meier product-limit method and between-group differences were analyzed by log-rank tests. The cumulative incidences of NRM, relapse, acute GVHD (aGVHD) and chronic GVHD (cGVHD) were calculated using Gray’s subdistribution method to account for the presence of competing risks.8 All analyses were two-sided, and significance was set at a P-value of 0.05. Statistical analyses were performed using statistical packages cmprsk (http://biowww.dfci.harvard.edu/~gray) for competing risk analysis and SAS 9.2 (SAS Institutes, Cary, NC, USA) for all other analyses.

In conclusion, our results suggest that combining G-CSF-mobilized PBSC with Hopkins NMA PT-CY haplo-HSCT regimen is associated with low NRM, encouraging rates of stable donor engraftment and no late graft failures. Despite a high median T-cell dose, aGVHD rate of 41% and cGVHD rate of 8% are comparable to those reported by other groups using more aggressive myeloablative conditioning regimens.2,3,5 The 1-year OS of 62% and RFS of 53% are highly encouraging considering the fact that approximately one-third had prior HSCT and half of our patients underwent transplant with active disease. Although our study is limited by a small number of patients with relatively short follow-up these results suggest G-CSF-mobilized PBSC is a reasonable substitute for marrow as a graft source for haplo-HSCT on PT-CY platform using less intensive NMA conditioning regimen for patients.

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References

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Authors and Affiliations

  1. Division of Hospital Medicine, Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA

    P K Bhamidipati

  2. Division of Oncology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA

    J F DiPersio, K Stokerl-Goldstein, A Rashidi, G L Uy, P Westervelt, R Vij, M A Schroeder, C N Abboud, J W Keller, T A Fehniger & R Romee

  3. Department of Biostatistics, Washington University School of Medicine, Saint Louis, MO, USA

    F Gao

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Correspondence to R Romee.

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Bhamidipati, P., DiPersio, J., Stokerl-Goldstein, K. et al. Haploidentical transplantation using G-CSF-mobilized T-cell replete PBSCs and post-transplantation CY after non-myeloablative conditioning is safe and is associated with favorable outcomes. Bone Marrow Transplant 49, 1124–1126 (2014). https://doi.org/10.1038/bmt.2014.108

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