Fever is a common early complication after infusion of stem cells in patients undergoing T-replete HLA haploidentical transplantation using post-transplant cyclophosphamide (PTCY). We analyzed the records of 172 haploidentical transplant patients to identify risk factors and to assess the impact of such fevers on transplant morbidity and mortality. One hundred and seventy-two patients received haploidential hematopoietic stem cell transplantation (haplo-HSCT) using PBSC (n = 103) or marrow (n = 69) grafts. One hundred and forty patients (81%) experienced fever (T ≥ 100.5 °F or >38 °C) with median onset on d + 2. Compared to patients who did not develop fevers, patients with fevers received higher median CD34+ cell dose (5.00 vs. 3.08 × 106/kg, p < 0.001), CD3+ cell dose (12.8 vs. 4.5 × 107/kg), were more likely to have received a myeloablative regimen (50% vs. 9%, p < 0.001), and PBSC source (71% vs. 9%, p < 0.001). Cox model showed that fever had no impact on TRM, GVHD, OS, and DFS. In the logistic regression to identify correlation with fevers, higher degree of HLA mismatches and use of PBSC were all predictors of developing fever. Fevers between infusion of the T-Cell replete graft and administration of PTCY are very common in Haplo-HSCT. This complication is transient and had no impact on post-transplant morbidity and mortality.
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Luznik L, O’Donnell PV, Symons HJ, Chen AR, Leffell MS, Zahurak M, et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2008;14:641–50.
Ciurea S. O., Zhang M.-J., Bacigalupo A., Bashey A., Appelbaum F. R., Antin J. H., et al. Survival after T-cell replete haplo-identical related donor transplant using post-transplant cyclophosphamide compared with matched unrelated donor transplant for acute myeloid leukemia. Blood. 2015;126:1033–40.
Brunstein CG, Fuchs EJ, Carter SL, Karanes C, Costa LJ, Wu J, et al. Alternative donor transplantation after reduced intensity conditioning: results of parallel phase 2 trials using partially HLA-mismatched related bone marrow or unrelated double umbilical cord blood grafts. Blood. 2011;118:282–8.
Luznik L, Jalla S, Engstrom LW, Iannone R, Fuchs EJ. Durable engraftment of major histocompatibility complex-incompatible cells after nonmyeloablative conditioning with fludarabine, low-dose total body irradiation, and posttransplantation cyclophosphamide. Blood. 2001;98:3456–64.
Solomon SR, Sizemore CA, Sanacore M, Zhang X, Brown S, Holland HK, et al. Total body irradiation-based myeloablative haploidentical stem cell transplantation is a safe and effective alternative to unrelated donor transplantation in patients without matched sibling donors. Biol Blood Marrow Transplant. 2015;21:1299–307.
O’Donnell PV, Eapen M, Horowitz MM, Logan BR, DiGilio A, Brunstein C, et al. Comparable outcomes with marrow or peripheral blood as stem cell sources for hematopoietic cell transplantation from haploidentical donors after non-ablative conditioning: a matched-pair analysis. Bone Marrow Transplant. 2016;51:1599–601.
Bashey A, Zhang X, Jackson K, Brown S, Ridgeway M, Solh M, et al. Comparison of outcomes of hematopoietic cell transplants from T-replete haploidentical donors using post-transplantation cyclophosphamide with 10 of 10 HLA-A, -B, -C, -DRB1, and -DQB1 allele-matched unrelated donors and HLA-identical sibling donors: a multivariable analysis including disease risk index. Biol Blood Marrow Transplant. 2016;22:125–33.
Abboud R, Keller J, Slade M, DiPersio JF, Westervelt P, Rettig MP, et al. Severe cytokine-release syndrome after T cell-replete peripheral blood haploidentical donor transplantation is associated with poor survival and anti-IL-6 therapy is safe and well tolerated. Biol Blood Marrow Transplant. 2016;22:1851–60.
O’Donnell P, Raj K, Pagliuca A. High fever occurring 4 to 5 days post-transplant of haploidentical bone marrow or peripheral blood stem cells after reduced-intensity conditioning associated with the use of post-transplant cyclophosphamide as prophylaxis for graft-versus-host disease. Biol Blood Marrow Transplant. 2015;21:197–8.
Arango M, Combariza JF. Fever after peripheral blood stem cell infusion in haploidentical transplantation with post-transplant cyclophosphamide. Hematol Oncol Stem Cell Ther. 2017;10:79–84.
Lee DW, Gardner R, Porter DL, Louis CU, Ahmed N, Jensen M, et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014;124:188–95.
Raj RV, Hamadani M, Szabo A, Pasquini MC, Shah NN, Drobyski WR, et al. Peripheral blood grafts for T-cell replete haploidentical transplantation increase the incidence and severity of cytokine release syndrome. Biol Blood Marrow Transplant. 2018;24:1664–70.
Bashey A, Zhang X, Sizemore CA, Manion K, Brown S, Holland HK, et al. T-cell-replete HLA-haploidentical hematopoietic transplantation for hematologic malignancies using post-transplantation cyclophosphamide results in outcomes equivalent to those of contemporaneous HLA-matched related and unrelated donor transplantation. J Clin Oncol. 2013;31:1310–6.
Grosso D, Carabasi M, Filicko-O’Hara J, Kasner M, Wagner JL, Colombe B, et al. A 2-step approach to myeloablative haploidentical stem cell transplantation: a phase 1/2 trial performed with optimized T-cell dosing. Blood. 2011;118:4732–9.
Grosso D, Gaballa S, Alpdogan O, Carabasi M, Filicko-O’Hara J, Kasner M, et al. A two-step approach to myeloablative haploidentical transplantation: low nonrelapse mortality and high survival confirmed in patients with earlier stage disease. Biol Blood Marrow Transplant. 2015;21:646–52.
McCurdy SR, Muth ST, Tsai HL, Symons HJ, Huff CA, Matsui WH, et al. Early fever after haploidentical bone marrow transplantation correlates with class II HLA-mismatching and myeloablation but not outcomes. Biol Blood Marrow Transplant. 2018;24:2056–64.
Teachey DT, Lacey SF, Shaw PA, Melenhorst JJ, Maude SL, Frey N, et al. Identification of predictive biomarkers for cytokine release syndrome after chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia. Cancer Discov. 2016;6:664–79.
Holtzman NLM, Badros A, Kocoglu M, Minas N, et al. Tocilizumab is effective therapy for cytokine release syndrome after haploidentical peripheral blood stem cell transplantation with post-transplant cyclophosphamide. Biol Blood Marrow Transplant. 2016;22:S324.
This study was presented at ASBMT 2017, Orlando, Florida.
Conflict of interest
The authors declare that they have no conflict of interest.
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