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Impact of conditioning intensity in T-replete haplo-identical stem cell transplantation for acute leukemia: a report from the acute leukemia working party of the EBMT.
J Hematol Oncol. 2016 Mar 15; 9:25.JH

Abstract

BACKGROUND

Increasing numbers of patients are receiving haplo-identical stem cell transplantation (haplo-SCT) for treatment of acute leukemia with reduced intensity (RIC) or myeloablative (MAC) conditioning regimens. The impact of conditioning intensity in haplo-SCT is unknown.

METHODS

We performed a retrospective registry-based study comparing outcomes after T-replete haplo-SCT for patients with acute myeloid (AML) or lymphoid leukemia (ALL) after RIC (n = 271) and MAC (n = 425). Regimens were classified as MAC or RIC based on published criteria.

RESULTS

A combination of post-transplant cyclophosphamide (PT-Cy) with one calcineurin inhibitor and mycophenolate mofetil (PT-Cy-based regimen) for graft-versus-host disease (GVHD) prophylaxis was used in 66 (25%) patients in RIC and 125 (32%) in MAC groups. Patients of RIC group were older and had been transplanted more recently and more frequently for AML with active disease at transplant. Percentage of engraftment (90 vs. 92%; p = 0.58) and day 100 grade II to IV acute GVHD (24 vs. 29%, p = 0.23) were not different between RIC and MAC groups. Multivariable analyses, run separately in AML and ALL, showed a trend toward higher relapse incidence with RIC in comparison to MAC in AML (hazard ratio (HR) 1.34, p = 0.09), and no difference in both AML and ALL in terms of non-relapse mortality (NRM) chronic GVHD and leukemia-free survival. There was no impact of conditioning regimen intensity in overall survival (OS) in AML (HR = 0.97, p = 0.79) but a trend for worse OS with RIC in ALL (HR = 1.44, p = 0.10). The main factor impacting outcomes was disease status at transplantation (HR ≥ 1.4, p ≤ 0.01). GVHD prophylaxis with PT-Cy-based regimen was independently associated with reduced NRM (HR 0.63, p = 0.02) without impact on relapse incidence (HR 0.99, p = 0.94).

CONCLUSIONS

These data suggest that T-replete haplo-SCT with both RIC and MAC, in particular associated with PT-Cy, are valid options in first line treatment of high risk AML or ALL.

Authors+Show Affiliations

Service d'Hématologie et de Thérapie cellulaire, Saint Antoine Hospital, Paris, France. mt_rubio@hotmail.com. INSERM UMR 938, Paris, France. mt_rubio@hotmail.com. Université Pierre et Marie Curie, Paris, France. mt_rubio@hotmail.com. Acute Leukemia Working Party of EBMT, Paris, France. mt_rubio@hotmail.com.Acute Leukemia Working Party of EBMT, Paris, France. Vanderbilt University Medical Center, Nashville, TN, USA.Service d'Hématologie et de Thérapie cellulaire, Saint Antoine Hospital, Paris, France. INSERM UMR 938, Paris, France. Université Pierre et Marie Curie, Paris, France. Acute Leukemia Working Party of EBMT, Paris, France. EBMT Paris study office/CEREST-TC, Paris, France.Acute Leukemia Working Party of EBMT, Paris, France. Ospedale San Raffaele s.r.l., Ematologia, Milan, Italy.Service d'Hématologie et de Thérapie cellulaire, Saint Antoine Hospital, Paris, France. INSERM UMR 938, Paris, France. Université Pierre et Marie Curie, Paris, France. Acute Leukemia Working Party of EBMT, Paris, France. EBMT Paris study office/CEREST-TC, Paris, France.Ospedale San Raffaele s.r.l., Ematologia, Milan, Italy.Department of Haematology II, Ospedale San Martino, Genoa, Italy.Rome Transplant Network, Stem Cell Transplant Unit, Tor Vergata University, Rome, Italy.Stem Cell Transplant Unit, Medical Park Hospitals, Antalya, Turkey.Department of Bone Marrow Transplantation, University Hospital, Essen, Germany.Bone Marrow Transplantation Department, Anadolu Medical Center Hospital, Kocaeli, Turkey.Department of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China.Ospedale Civile BMT Center, Pescara, Italy.Department of Internal Medicine III, Ludwig-Maximilians-University Hospital of Munich-Grosshadern, Munich, Germany.SPb State I. Pavlov Medical University, St. Petersburg, Russia.Klinikum Augsburg, University of Munich, Munich, Germany.Department of Bone Marrow Transplantation and Hemato-Oncology, Cancer Center, Gliwice, Poland.Service d'Hématologie et de Thérapie cellulaire, Saint Antoine Hospital, Paris, France. INSERM UMR 938, Paris, France. Université Pierre et Marie Curie, Paris, France. Acute Leukemia Working Party of EBMT, Paris, France. EBMT Paris study office/CEREST-TC, Paris, France.Université Pierre et Marie Curie, Paris, France. Hematology Division, Chaim Sheba Medical Center, Tel Hashomer, Israel.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26980295

Citation

Rubio, Marie T., et al. "Impact of Conditioning Intensity in T-replete Haplo-identical Stem Cell Transplantation for Acute Leukemia: a Report From the Acute Leukemia Working Party of the EBMT." Journal of Hematology & Oncology, vol. 9, 2016, p. 25.
Rubio MT, Savani BN, Labopin M, et al. Impact of conditioning intensity in T-replete haplo-identical stem cell transplantation for acute leukemia: a report from the acute leukemia working party of the EBMT. J Hematol Oncol. 2016;9:25.
Rubio, M. T., Savani, B. N., Labopin, M., Piemontese, S., Polge, E., Ciceri, F., Bacigalupo, A., Arcese, W., Koc, Y., Beelen, D., Gülbas, Z., Wu, D., Santarone, S., Tischer, J., Afanasyev, B., Schmid, C., Giebel, S., Mohty, M., & Nagler, A. (2016). Impact of conditioning intensity in T-replete haplo-identical stem cell transplantation for acute leukemia: a report from the acute leukemia working party of the EBMT. Journal of Hematology & Oncology, 9, 25. https://doi.org/10.1186/s13045-016-0248-3
Rubio MT, et al. Impact of Conditioning Intensity in T-replete Haplo-identical Stem Cell Transplantation for Acute Leukemia: a Report From the Acute Leukemia Working Party of the EBMT. J Hematol Oncol. 2016 Mar 15;9:25. PubMed PMID: 26980295.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Impact of conditioning intensity in T-replete haplo-identical stem cell transplantation for acute leukemia: a report from the acute leukemia working party of the EBMT. AU - Rubio,Marie T, AU - Savani,Bipin N, AU - Labopin,Myriam, AU - Piemontese,Simona, AU - Polge,Emmanuelle, AU - Ciceri,Fabio, AU - Bacigalupo,Andrea, AU - Arcese,William, AU - Koc,Yener, AU - Beelen,Dietrich, AU - Gülbas,Zafer, AU - Wu,Depei, AU - Santarone,Stella, AU - Tischer,Johanna, AU - Afanasyev,Boris, AU - Schmid,Christoph, AU - Giebel,Sebastian, AU - Mohty,Mohamad, AU - Nagler,Arnon, Y1 - 2016/03/15/ PY - 2016/01/06/received PY - 2016/02/24/accepted PY - 2016/3/17/entrez PY - 2016/3/17/pubmed PY - 2016/10/19/medline KW - Acute Leukemia KW - Allogeneic stem cell transplantation KW - Anti-leukemic effect KW - Conditioning regimen KW - Haplo-identical donor KW - Toxicity SP - 25 EP - 25 JF - Journal of hematology & oncology JO - J Hematol Oncol VL - 9 N2 - BACKGROUND: Increasing numbers of patients are receiving haplo-identical stem cell transplantation (haplo-SCT) for treatment of acute leukemia with reduced intensity (RIC) or myeloablative (MAC) conditioning regimens. The impact of conditioning intensity in haplo-SCT is unknown. METHODS: We performed a retrospective registry-based study comparing outcomes after T-replete haplo-SCT for patients with acute myeloid (AML) or lymphoid leukemia (ALL) after RIC (n = 271) and MAC (n = 425). Regimens were classified as MAC or RIC based on published criteria. RESULTS: A combination of post-transplant cyclophosphamide (PT-Cy) with one calcineurin inhibitor and mycophenolate mofetil (PT-Cy-based regimen) for graft-versus-host disease (GVHD) prophylaxis was used in 66 (25%) patients in RIC and 125 (32%) in MAC groups. Patients of RIC group were older and had been transplanted more recently and more frequently for AML with active disease at transplant. Percentage of engraftment (90 vs. 92%; p = 0.58) and day 100 grade II to IV acute GVHD (24 vs. 29%, p = 0.23) were not different between RIC and MAC groups. Multivariable analyses, run separately in AML and ALL, showed a trend toward higher relapse incidence with RIC in comparison to MAC in AML (hazard ratio (HR) 1.34, p = 0.09), and no difference in both AML and ALL in terms of non-relapse mortality (NRM) chronic GVHD and leukemia-free survival. There was no impact of conditioning regimen intensity in overall survival (OS) in AML (HR = 0.97, p = 0.79) but a trend for worse OS with RIC in ALL (HR = 1.44, p = 0.10). The main factor impacting outcomes was disease status at transplantation (HR ≥ 1.4, p ≤ 0.01). GVHD prophylaxis with PT-Cy-based regimen was independently associated with reduced NRM (HR 0.63, p = 0.02) without impact on relapse incidence (HR 0.99, p = 0.94). CONCLUSIONS: These data suggest that T-replete haplo-SCT with both RIC and MAC, in particular associated with PT-Cy, are valid options in first line treatment of high risk AML or ALL. SN - 1756-8722 UR - https://www.unboundmedicine.com/medline/citation/26980295/Impact_of_conditioning_intensity_in_T_replete_haplo_identical_stem_cell_transplantation_for_acute_leukemia:_a_report_from_the_acute_leukemia_working_party_of_the_EBMT_ L2 - https://jhoonline.biomedcentral.com/articles/10.1186/s13045-016-0248-3 DB - PRIME DP - Unbound Medicine ER -