The role of hematopoietic cell transplantation (HCT) in adults with acute lymphoblastic leukemia (ALL) is reviewed and critically evaluated in this systematic evidence-based review. Specific criteria were used for searching the published literature and for grading the quality and strength of the evidence and the strength of the recommendations. A panel of ALL experts developed consensus on the treatment recommendations based on the evidence. Allogeneic HCT offers a survival benefit in selected patients with ALL, and this review summarizes the standard indications as well as the areas of controversy. There is now greater experience with pediatric-inspired chemotherapy regimens that has transformed upfront therapy for adult ALL, resulting in higher remission rates and overall survival. This in turn has increased the equipoise around decision making for ALL in first complete remission (CR1) when there is no measurable residual disease (MRD) at the end of induction and/or consolidation. Randomized studies are needed for adults with ALL to compare allogeneic HCT in CR1 with pediatric-inspired chemotherapy alone. Indications for transplantation in the evolving landscape of MRD assessments and novel targeted and immune therapeutics remain important areas of investigation.
Bibliographical noteFunding Information:
Conflict of interest statement: Z.D. has received research support from Incyte. A.S.A. has received research support from Amgen , Pfizer , MacroGenics, Abbvie, GlycoMimetics, and Takeda and consulting fees and honoraria from Pfizer and KiTE Pharmaceuticals, Glycomimetics, and Novartis. V.B. has received funding from GT Biopharma, Incyte, Gamida-Cell, UNUM Therapeutics, and Novartis and has served on advisory boards for Seattle Genetics and UNUM Therapeutics. R.D.C. reports research support from Amgen , Incyte, Kite Pharma/ Gilead Sciences , Merck & Co, Pfizer , and Vanda Pharmaceuticals ; consultancy with Amgen and Pfizer; honoraria from Pfizer; and employment and stock holdings with Seattle Genetics (spouse). P.K. has received research support from Amgen and serves as a consultant for Jazz Pharmaceuticals and on the advisory board for Pfizer . J.M.R serves as a consultant for BioSight. M.D.S. reports research support from Teva Pharmaceutical and consulting for Abbvie and serves on advisory boards for Pfizer, Amgen, and Jazz Pharmaceuticals. Y.I. has received honoraria from Astellas Pharma, Novartis, Chugai Pharmaceutical, Sumitomo Dainippon Pharma, MSD KK (a subsidiary of Merck & Co.), and Meiji Seika Pharma. A.K. serves on advisory boards for Celgene and Janssen Pharmaceutica. C.S.S. reports paid consultancy on advisory boards for Juno Therapeutics, Sanofi-Genzyme, Spectrum Pharmaceuticals, Novartis, Genmab, Precision Biosciences, Kite (a Gilead Company), Celgene and GSK and research support from Juno Therapeutics and Sanofi - Genzyme . M.A.P. has received honoraria from AbbVie , Bellicum Pharmaceuticals , Bristol-Myers Squibb , Incyte, Merck & Co, Novartis, Nektar Therapeutics, Omeros, and Takeda; serves on DSMBs for Servier and Medigene and on scientific advisory boards for MolMed and NexImmune; has received research support for clinical trials from Incyte, Kite/Gilead, and Miltenyi Biotec; and serves in a volunteer capacity as a member of the Board of Directors of American Society for Transplantation and Cellular Therapy and Be the Match (National Marrow Donor Program), as well as on the CIBMTR Cellular Immunotherapy Data Resource Committee. D.W. reports research support from Incyte and consultancy for Fate Therapeutics and Pharmacyclics. The other authors report no conflicts of interest.
- Acute lymphoblastic leukemia
- Allogeneic hematopoietic cell transplantation
- Autologous stem cell transplantation
- Evidence-based review