Mobilized Peripheral Blood Stem Cells Versus Unstimulated Bone Marrow As a Graft Source for T-Cell-Replete Haploidentical Donor Transplantation Using Post-Transplant Cyclophosphamide

Asad Bashey, Mei-Jie Zhang, Shannon R McCurdy, Andrew St Martin, Trevor Argall, Claudio Anasetti, Stefan O Ciurea, Omotayo Fasan, Sameh Gaballa, Mehdi Hamadani, Pashna Munshi, Monzr M Al Malki, Ryotaro Nakamura, Paul V O'Donnell, Miguel-Angel Perales, Kavita Raj, Rizwan Romee, Scott Rowley, Vanderson Rocha, Rachel B Salit, Melhem Solh, Robert J Soiffer, Ephraim Joseph Fuchs, Mary Eapen, Asad Bashey, Mei-Jie Zhang, Shannon R McCurdy, Andrew St Martin, Trevor Argall, Claudio Anasetti, Stefan O Ciurea, Omotayo Fasan, Sameh Gaballa, Mehdi Hamadani, Pashna Munshi, Monzr M Al Malki, Ryotaro Nakamura, Paul V O'Donnell, Miguel-Angel Perales, Kavita Raj, Rizwan Romee, Scott Rowley, Vanderson Rocha, Rachel B Salit, Melhem Solh, Robert J Soiffer, Ephraim Joseph Fuchs, Mary Eapen

Abstract

Purpose T-cell-replete HLA-haploidentical donor hematopoietic transplantation using post-transplant cyclophosphamide was originally described using bone marrow (BM). With increasing use of mobilized peripheral blood (PB), we compared transplant outcomes after PB and BM transplants. Patients and Methods A total of 681 patients with hematologic malignancy who underwent transplantation in the United States between 2009 and 2014 received BM (n = 481) or PB (n = 190) grafts. Cox regression models were built to examine differences in transplant outcomes by graft type, adjusting for patient, disease, and transplant characteristics. Results Hematopoietic recovery was similar after transplantation of BM and PB (28-day neutrophil recovery, 88% v 93%, P = .07; 100-day platelet recovery, 88% v 85%, P = .33). Risks of grade 2 to 4 acute (hazard ratio [HR], 0.45; P < .001) and chronic (HR, 0.35; P < .001) graft-versus-host disease were lower with transplantation of BM compared with PB. There were no significant differences in overall survival by graft type (HR, 0.99; P = .98), with rates of 54% and 57% at 2 years after transplantation of BM and PB, respectively. There were no differences in nonrelapse mortality risks (HR, 0.92; P = .74) but relapse risks were higher after transplantation of BM (HR, 1.49; P = .009). Additional exploration confirmed that the higher relapse risks after transplantation of BM were limited to patients with leukemia (HR, 1.73; P = .002) and not lymphoma (HR, 0.87; P = .64). Conclusion PB and BM grafts are suitable for haploidentical transplantation with the post-transplant cyclophosphamide approach but with differing patterns of treatment failure. Although, to our knowledge, this is the most comprehensive comparison, these findings must be validated in a randomized prospective comparison with adequate follow-up.

Figures

Fig 1.
Fig 1.
(A) The 6-month incidence of grades 2 to 4 (left panel) acute graft-versus-host disease (GVHD) adjusted for conditioning regimen intensity were 25% (95% CI, 21% to 29%) and 42% (95% CI, 35% to 50%) after bone marrow (BM) and peripheral blood (PB) transplants, respectively. The 6-month incidence of grades 3 to 4 (right panel) acute GVHD adjusted for conditioning regimen intensity were 7% (95% CI, 5% to 10%) and 10% (95% CI, 6% to 15%) after BM and PB transplants, respectively. (B) The 2-year incidence of chronic GVHD adjusted for performance score were 20% (95% CI, 16% to 24%) and 41% (95% CI, 33% to 48%) after BM and PB transplants, respectively.
Fig 2.
Fig 2.
The 2-year probabilities of overall survival adjusted for age, cytomegalovirus serostatus, disease risk index, and transplant conditioning regimen intensity were 54% (95% CI, 49% to 59%) and 57% (95% CI, 49% to 65%) after bone marrow (BM) and peripheral blood (PB) transplants.
Fig 3.
Fig 3.
(A) The 2-year incidence of nonrelapse mortality adjusted for age, cytomegalovirus serostatus, and transplant conditioning regimen intensity was 17% (95% CI, 13% to 21%) and 16% (95% CI, 11% to 22%) after bone marrow (BM) and peripheral blood (PB) transplants, respectively. (B) The 2-year incidence of relapse/progression adjusted for disease risk index was 45% (95% CI, 41% to 50%) and 28% (95% CI, 22% to 34%) after BM and PB transplants.
Fig 4.
Fig 4.
The 2-year probabilities of progression-free survival adjusted for age, cytomegalovirus serostatus and disease risk index were 41% (95% CI, 36% to 45%) and 54% (95% CI, 47% to 61%) after bone marrow (BM) and peripheral blood (PB) transplants.

Source: PubMed

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