TY - JOUR
T1 - Allogeneic Blood or Marrow Transplantation with High-Dose Post-Transplantation Cyclophosphamide for Acute Lymphoblastic Leukemia in Patients Age ≥55 Years
AU - Webster, Jonathan A.
AU - Reed, Madison
AU - Tsai, Hua Ling
AU - Ambinder, Alexander
AU - Jain, Tania
AU - Dezern, Amy E.
AU - Levis, Mark J.
AU - Showel, Margaret M.
AU - Prince, Gabrielle T.
AU - Hourigan, Christopher S.
AU - Gladstone, Douglas E.
AU - Bolanos-Meade, Javier
AU - Gondek, Lukasz P.
AU - Ghiaur, Gabriel
AU - Dalton, W. Brian
AU - Paul, Suman
AU - Fuchs, Ephraim J.
AU - Gocke, Christian B.
AU - Ali, Syed Abbas
AU - Huff, Carol Ann
AU - Borrello, Ivan M.
AU - Swinnen, Lode
AU - Wagner-Johnston, Nina
AU - Ambinder, Richard F.
AU - Luznik, Leo
AU - Gojo, Ivana
AU - Smith, B. Douglas
AU - Varadhan, Ravi
AU - Jones, Richard J.
AU - Imus, Philip H.
N1 - Funding Information:
Conflict of interest statement: J.A.W., I.G., and M.J.L. have received honoraria from Amgen. J.A.W. and B.D.S. have received honoraria from Pfizer. I.G. has served as a consultant for ImmunoGen, Gilead, Bristol Myers Squibb, Certara, Johnson & Johnson, and Ono Pharmaceutical. I.G. has received research support from Amgen, Merck, Amphivena, Gilead, Genetech, and Celgene. The National Heart, Lung and Blood Institute receives research funding for the C.S.H. laboratory from Sellas and the National Institutes of Health's AML MRD Biomarkers Consortium. The other authors have no conflicts of interest to report.
Funding Information:
Financial disclosure: This work was supported by National Institutes of Health Grants P01 CA225618 and P30 CA06973.
Publisher Copyright:
© 2022 The American Society for Transplantation and Cellular Therapy
PY - 2023/3
Y1 - 2023/3
N2 - Patients age ≥55 years with acute lymphoblastic leukemia (ALL) fare poorly with conventional chemotherapy, with a 5-year overall survival (OS) of ∼20%. Tyrosine kinase inhibitors and novel B cell-targeted therapies can improve outcomes, but rates of relapse and death in remission remain high. Allogeneic blood or marrow transplantation (alloBMT) provides an alternative consolidation strategy, and post-transplantation cyclophosphamide (PTCy) facilitates HLA-mismatched transplantations with low rates of nonrelapse mortality (NRM) and graft-versus-host disease (GVHD). The transplantation database at Johns Hopkins was queried for patients age ≥55 years who underwent alloBMT for ALL using PTCy. The database included 77 such patients. Most received reduced-intensity conditioning (RIC) (88.3%), were in first complete remission (CR1) (85.7%), and had B-lineage disease (90.9%). For the entire cohort, 5-year relapse-free survival (RFS) and overall survival (OS) were 46% (95% confidence interval [CI], 34% to 57%) and 49% (95% CI, 37% to 60%), respectively. Grade III-IV acute GVHD occurred in only 3% of patients, and chronic GVHD occurred in 13%. In multivariable analysis, myeloablative conditioning led to worse RFS (hazard ratio [HR], 4.65; P = .001), whereas transplantation in CR1 (HR, .30; P = .004) and transplantation for Philadelphia chromosome-positive (Ph+) ALL versus T-ALL (HR, .29; P = .03) were associated with improved RFS. Of the 54 patients who underwent RIC alloBMT in CR1 for B-ALL, the 5-year RFS and OS were 62% (95% CI, 47% to 74%) and 65% (95% CI, 51% to 77%), respectively, with a 5-year relapse incidence of 16% (95% CI, 7% to 27%) and an NRM of 24% (95% CI, 13% to 36%). RIC alloBMT with PTCy in CR1 represents a promising consolidation strategy for B-ALL patients age ≥55 years.
AB - Patients age ≥55 years with acute lymphoblastic leukemia (ALL) fare poorly with conventional chemotherapy, with a 5-year overall survival (OS) of ∼20%. Tyrosine kinase inhibitors and novel B cell-targeted therapies can improve outcomes, but rates of relapse and death in remission remain high. Allogeneic blood or marrow transplantation (alloBMT) provides an alternative consolidation strategy, and post-transplantation cyclophosphamide (PTCy) facilitates HLA-mismatched transplantations with low rates of nonrelapse mortality (NRM) and graft-versus-host disease (GVHD). The transplantation database at Johns Hopkins was queried for patients age ≥55 years who underwent alloBMT for ALL using PTCy. The database included 77 such patients. Most received reduced-intensity conditioning (RIC) (88.3%), were in first complete remission (CR1) (85.7%), and had B-lineage disease (90.9%). For the entire cohort, 5-year relapse-free survival (RFS) and overall survival (OS) were 46% (95% confidence interval [CI], 34% to 57%) and 49% (95% CI, 37% to 60%), respectively. Grade III-IV acute GVHD occurred in only 3% of patients, and chronic GVHD occurred in 13%. In multivariable analysis, myeloablative conditioning led to worse RFS (hazard ratio [HR], 4.65; P = .001), whereas transplantation in CR1 (HR, .30; P = .004) and transplantation for Philadelphia chromosome-positive (Ph+) ALL versus T-ALL (HR, .29; P = .03) were associated with improved RFS. Of the 54 patients who underwent RIC alloBMT in CR1 for B-ALL, the 5-year RFS and OS were 62% (95% CI, 47% to 74%) and 65% (95% CI, 51% to 77%), respectively, with a 5-year relapse incidence of 16% (95% CI, 7% to 27%) and an NRM of 24% (95% CI, 13% to 36%). RIC alloBMT with PTCy in CR1 represents a promising consolidation strategy for B-ALL patients age ≥55 years.
KW - Acute lymphoblastic leukemia
KW - Allogeneic blood or marrow transplantation
KW - Elderly
KW - Posttransplantation cyclophosphamide
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UR - http://www.scopus.com/inward/citedby.url?scp=85146588091&partnerID=8YFLogxK
U2 - 10.1016/j.jtct.2022.12.018
DO - 10.1016/j.jtct.2022.12.018
M3 - Article
C2 - 36587740
AN - SCOPUS:85146588091
SN - 2666-6367
VL - 29
SP - 182.e1-182.e8
JO - Transplantation and Cellular Therapy
JF - Transplantation and Cellular Therapy
IS - 3
ER -