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A Two-Step Haploidentical Versus a Two-Step Matched Related Allogeneic Myeloablative Peripheral Blood Stem Cell Transplantation.
Biol Blood Marrow Transplant. 2016 Jan; 22(1):141-8.BB

Abstract

Haploidentical stem cell transplantation (SCT) offers a transplantation option to patients who lack an HLA-matched donor. We developed a 2-step approach to myeloablative allogeneic hematopoietic stem cell transplantation for patients with haploidentical or matched related (MR) donors. In this approach, the lymphoid and myeloid portions of the graft are administered in 2 separate steps to allow fixed T cell dosing. Cyclophosphamide is used for T cell tolerization. Given a uniform conditioning regimen, graft T cell dose, and graft-versus-host disease (GVHD) prophylaxis strategy, we compared immune reconstitution and clinical outcomes in patients undergoing 2-step haploidentical versus 2-step MR SCT. We retrospectively compared data on patients undergoing a 2-step haploidentical (n = 50) or MR (n = 27) peripheral blood SCT for high-risk hematological malignancies and aplastic anemia. Both groups received myeloablative total body irradiation conditioning. Immune reconstitution data included flow cytometric assessment of T cell subsets at day 28 and 90 after SCT. Both groups showed comparable early immune recovery in all assessed T cell subsets except for the median CD3/CD8 cell count, which was higher in the MR group at day 28 compared with that in the haploidentical group. The 3-year probability of overall survival was 70% in the haploidentical group and 71% in the MR group (P = .81), while the 3-year progression-free survival was 68% in the haploidentical group and 70% in the MR group (P = .97). The 3-year cumulative incidence of nonrelapse mortality was 10% in the haploidentical group and 4% in the MR group (P = .34). The 3-year cumulative incidence of relapse was 21% in the haploidentical group and 27% in the MR group (P = .93). The 100-day cumulative incidence of overall grades II to IV acute GVHD was higher in the haploidentical group compared with that in the MR group (40% versus 8%, P < .001), whereas the grades III and IV acute GVHD was not statistically different between both groups (haploidentical, 6%; MR, 4%; P = .49). The cumulative incidence of cytomegalovirus reactivation was also higher in the haploidentical group compared to the MR group (haploidentical, 68%; MR, 19%; P < .001). There were no deaths from GVHD in either group. Using an identical conditioning regimen, graft T cell dose, and GVHD prophylaxis strategy, comparable early immune recovery and clinical outcomes were observed in the 2-step haploidentical and MR SCT recipients.

Authors+Show Affiliations

Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania. Electronic address: samehgaballa@gmail.com.Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania.Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania.Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.Department of Pharmacy, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.

Pub Type(s)

Clinical Trial
Comparative Study
Journal Article

Language

eng

PubMed ID

26415558

Citation

Gaballa, Sameh, et al. "A Two-Step Haploidentical Versus a Two-Step Matched Related Allogeneic Myeloablative Peripheral Blood Stem Cell Transplantation." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, vol. 22, no. 1, 2016, pp. 141-8.
Gaballa S, Palmisiano N, Alpdogan O, et al. A Two-Step Haploidentical Versus a Two-Step Matched Related Allogeneic Myeloablative Peripheral Blood Stem Cell Transplantation. Biol Blood Marrow Transplant. 2016;22(1):141-8.
Gaballa, S., Palmisiano, N., Alpdogan, O., Carabasi, M., Filicko-O'Hara, J., Kasner, M., Kraft, W. K., Leiby, B., Martinez-Outschoorn, U., O'Hara, W., Pro, B., Rudolph, S., Sharma, M., Wagner, J. L., Weiss, M., Flomenberg, N., & Grosso, D. (2016). A Two-Step Haploidentical Versus a Two-Step Matched Related Allogeneic Myeloablative Peripheral Blood Stem Cell Transplantation. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, 22(1), 141-8. https://doi.org/10.1016/j.bbmt.2015.09.017
Gaballa S, et al. A Two-Step Haploidentical Versus a Two-Step Matched Related Allogeneic Myeloablative Peripheral Blood Stem Cell Transplantation. Biol Blood Marrow Transplant. 2016;22(1):141-8. PubMed PMID: 26415558.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A Two-Step Haploidentical Versus a Two-Step Matched Related Allogeneic Myeloablative Peripheral Blood Stem Cell Transplantation. AU - Gaballa,Sameh, AU - Palmisiano,Neil, AU - Alpdogan,Onder, AU - Carabasi,Matthew, AU - Filicko-O'Hara,Joanne, AU - Kasner,Margaret, AU - Kraft,Walter K, AU - Leiby,Benjamin, AU - Martinez-Outschoorn,Ubaldo, AU - O'Hara,William, AU - Pro,Barbara, AU - Rudolph,Shannon, AU - Sharma,Manish, AU - Wagner,John L, AU - Weiss,Mark, AU - Flomenberg,Neal, AU - Grosso,Dolores, Y1 - 2015/09/28/ PY - 2015/06/12/received PY - 2015/09/20/accepted PY - 2015/9/30/entrez PY - 2015/9/30/pubmed PY - 2016/9/30/medline KW - Haploidentical KW - Matched related KW - Myeloablative total body irradiation conditioning KW - Peripheral blood stem cell transplantation KW - Two-step approach SP - 141 EP - 8 JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol. Blood Marrow Transplant. VL - 22 IS - 1 N2 - Haploidentical stem cell transplantation (SCT) offers a transplantation option to patients who lack an HLA-matched donor. We developed a 2-step approach to myeloablative allogeneic hematopoietic stem cell transplantation for patients with haploidentical or matched related (MR) donors. In this approach, the lymphoid and myeloid portions of the graft are administered in 2 separate steps to allow fixed T cell dosing. Cyclophosphamide is used for T cell tolerization. Given a uniform conditioning regimen, graft T cell dose, and graft-versus-host disease (GVHD) prophylaxis strategy, we compared immune reconstitution and clinical outcomes in patients undergoing 2-step haploidentical versus 2-step MR SCT. We retrospectively compared data on patients undergoing a 2-step haploidentical (n = 50) or MR (n = 27) peripheral blood SCT for high-risk hematological malignancies and aplastic anemia. Both groups received myeloablative total body irradiation conditioning. Immune reconstitution data included flow cytometric assessment of T cell subsets at day 28 and 90 after SCT. Both groups showed comparable early immune recovery in all assessed T cell subsets except for the median CD3/CD8 cell count, which was higher in the MR group at day 28 compared with that in the haploidentical group. The 3-year probability of overall survival was 70% in the haploidentical group and 71% in the MR group (P = .81), while the 3-year progression-free survival was 68% in the haploidentical group and 70% in the MR group (P = .97). The 3-year cumulative incidence of nonrelapse mortality was 10% in the haploidentical group and 4% in the MR group (P = .34). The 3-year cumulative incidence of relapse was 21% in the haploidentical group and 27% in the MR group (P = .93). The 100-day cumulative incidence of overall grades II to IV acute GVHD was higher in the haploidentical group compared with that in the MR group (40% versus 8%, P < .001), whereas the grades III and IV acute GVHD was not statistically different between both groups (haploidentical, 6%; MR, 4%; P = .49). The cumulative incidence of cytomegalovirus reactivation was also higher in the haploidentical group compared to the MR group (haploidentical, 68%; MR, 19%; P < .001). There were no deaths from GVHD in either group. Using an identical conditioning regimen, graft T cell dose, and GVHD prophylaxis strategy, comparable early immune recovery and clinical outcomes were observed in the 2-step haploidentical and MR SCT recipients. SN - 1523-6536 UR - https://www.unboundmedicine.com/medline/citation/26415558/A_Two_Step_Haploidentical_Versus_a_Two_Step_Matched_Related_Allogeneic_Myeloablative_Peripheral_Blood_Stem_Cell_Transplantation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083-8791(15)00642-4 DB - PRIME DP - Unbound Medicine ER -