Eligibility Criteria for Patients Undergoing Allogeneic Hematopoietic Cell Transplantation

Restricted access

Eligibility assessment of a potential candidate for allogeneic hematopoietic cell transplantation (allo-HCT) is a complex yet vital component of pretransplant evaluation. Although no formal standardized consensus exists to guide this process, transplant centers follow institutional standard operating procedures and parameters to approve candidacy of an individual patient. Consideration for allo-HCT is dependent on a myriad of interrelated factors, including disease-related (eg, appropriate indication, disease status, prior therapies), patient-related (eg, age, functional status, frailty, comorbidities), psychosocial, and economic factors. A multidisciplinary approach is optimal for patient selection and requires the efforts of transplant coordinators, nurses, advanced practice providers, social workers, psychologists, financial specialists, and physicians. This article reviews the data and provides general guidelines that may be used in making an informed decision when evaluating a prospective candidate for allo-HCT. These recommendations are based on published data, expert commentary, reviews, and institutional practices. In the end, the eligibility assessment and decision to consider allo-HCT as the optimal choice of treatment for an individual patient are truly as much an “art” as it is the “science” of medicine, encompassing a multidisciplinary approach to minimize harm without compromising the curative potential—all essential doctrines of the Hippocratic Oath.

Submitted November 27, 2019; accepted for publication March 10, 2020.

Disclosures: Dr. Perales has disclosed that he has received support from NIH (award P01 CA23766) and NIH/NCI Cancer Center Support Grant (P30 CA008748); honoraria from Abbvie, Bellicum, Celgene, Bristol-Myers Squibb, Incyte, Merck, Novartis, Nektar Therapeutics, Omeros, and Takeda; serves as a scientific advisor for Cidara Therapeutics, Servier, and Medigene, MolMed, and NexImmune; and received grant/research support from Incyte, Kite/Gilead and Miltenyi Biotec. Dr. Hamadani has disclosed that he receives grant/research support from Takeda Pharmaceutical Company, Otsuka Pharmaceutical, Spectrum Pharmaceuticals, Astellas Pharma, Janssen R&D, Celgene Corporation, Merck, MedImmune, Seattle Genetics, and Millennium Pharmaceuticals; serves as a consultant for MedImmune LLC, Janssen R &D, Incyte Corporation, ADC Therapeutics, Cellerant Therapeutics, Celgene Corporation, Pharmacyclics & DOVA Oncology, Magenta Therapeutics, Omeros, and Verastem; and serves as a scientific advisor for Sanofi Genzyme, and AstraZeneca. Dr. Kanate has disclosed that he has no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors

Correspondence: Mehdi Hamadani, MD, Department of Medicine, Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, 9200 West Wisconsin Avenue, Suite C5500, Milwaukee, WI 53226. Email: mhamadani@mcw.edu
  • 1.

    D’Souza A, Fretham C. Current uses and outcomes of hematopoietic cell transplantation (HCT): CIBMTR summary slides, 2019. Accessed March 16, 2020. Available at: https://www.cibmtr.org

  • 2.

    Scott B, Sandmaier B. The evaluation and counseling of candidates for hematopoietic cell transplantation. In: Forman JS, Negrin RS, Antin JH, Appelbaum FR, eds. Thomas’ Hematopoietic Cell Transplantation, 5th ed. Boston, MA: Blackwell Publishing; 2016:349–365.

    • Crossref
    • Export Citation
  • 3.

    McDonald GB, Sandmaier BM, Mielcarek M, . Survival, nonrelapse mortality, and relapse-related mortality after allogeneic hematopoietic cell transplantation: comparing 2003-2007 versus 2013-2017 cohorts [published online January 21, 2020]. Ann Intern Med, doi: https://doi.org/10.7326/M19-2936

    • Search Google Scholar
    • Export Citation
  • 4.

    Timing Impact on Outcomes. Accessed November 1, 2019. Available at: https://bethematchclinical.org/transplant-indications-and-outcomes/additional-outcomes/timing-impact-on-outcomes

  • 5.

    Hamadani M, Craig M, Awan FT, . How we approach patient evaluation for hematopoietic stem cell transplantation. Bone Marrow Transplant 2010;45:12591268.

  • 6.

    Majhail NS, Farnia SH, Carpenter PA, . Indications for autologous and allogeneic hematopoietic cell transplantation: guidelines from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant 2015;21:18631869.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7.

    Perales MA, Ceberio I, Armand P, . Role of cytotoxic therapy with hematopoietic cell transplantation in the treatment of Hodgkin lymphoma: guidelines from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant 2015;21:971983.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    de Witte T, Bowen D, Robin M, . Allogeneic hematopoietic stem cell transplantation for MDS and CMML: recommendations from an international expert panel. Blood 2017;129:17531762.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Freytes CO, Zhang MJ, Carreras J, . Outcome of lower-intensity allogeneic transplantation in non-Hodgkin lymphoma after autologous transplantation failure. Biol Blood Marrow Transplant 2012;18:12551264.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Baron J, Wang ES. Gemtuzumab ozogamicin for the treatment of acute myeloid leukemia. Expert Rev Clin Pharmacol 2018;11:549559.

  • 11.

    Kantarjian HM, DeAngelo DJ, Stelljes M, . Inotuzumab ozogamicin versus standard of care in relapsed or refractory acute lymphoblastic leukemia: final report and long-term survival follow-up from the randomized, phase 3 INO-VATE study. Cancer 2019;125:24742487.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Sugio T, Kato K, Aoki T, . Mogamulizumab treatment prior to allogeneic hematopoietic stem cell transplantation induces severe acute graft-versus-host disease. Biol Blood Marrow Transplant 2016;22:16081614.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Merryman RW, Kim HT, Zinzani PL, . Safety and efficacy of allogeneic hematopoietic stem cell transplant after PD-1 blockade in relapsed/refractory lymphoma. Blood 2017;129:13801388.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Myers AL, Kawedia JD, Champlin RE, . Clarifying busulfan metabolism and drug interactions to support new therapeutic drug monitoring strategies: a comprehensive review. Expert Opin Drug Metab Toxicol 2017;13:901923.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Warlick ED, Cioc A, Defor T, . Allogeneic stem cell transplantation for adults with myelodysplastic syndromes: importance of pretransplant disease burden. Biol Blood Marrow Transplant 2009;15:3038.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Sarina B, Castagna L, Farina L, . Allogeneic transplantation improves the overall and progression-free survival of Hodgkin lymphoma patients relapsing after autologous transplantation: a retrospective study based on the time of HLA typing and donor availability. Blood 2010;115:36713677.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Fenske TS, Ahn KW, Graff TM, . Allogeneic transplantation provides durable remission in a subset of DLBCL patients relapsing after autologous transplantation. Br J Haematol 2016;174:235248.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18.

    Weisdorf DJ, Millard HR, Horowitz MM, . Allogeneic transplantation for advanced acute myeloid leukemia: the value of complete remission. Cancer 2017;123:20252034.

  • 19.

    Koreth J, Schlenk R, Kopecky KJ, . Allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission: systematic review and meta-analysis of prospective clinical trials. JAMA 2009;301:23492361.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Armand P, Gibson CJ, Cutler C, . A disease risk index for patients undergoing allogeneic stem cell transplantation. Blood 2012;120:905913.

  • 21.

    Armand P, Kim HT, Logan BR, . Validation and refinement of the Disease Risk Index for allogeneic stem cell transplantation. Blood 2014;123:36643671.

  • 22.

    Greenberg PL, Tuechler H, Schanz J, . Revised international prognostic scoring system for myelodysplastic syndromes. Blood 2012;120:24542465.

  • 23.

    Döhner H, Estey E, Grimwade D, . Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood 2017;129:424447.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24.

    Saber W, Opie S, Rizzo JD, . Outcomes after matched unrelated donor versus identical sibling hematopoietic cell transplantation in adults with acute myelogenous leukemia. Blood 2012;119:39083916.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Brunstein CG, Fuchs EJ, Carter SL, . 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;118:282288.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26.

    Kanate AS, Mussetti A, Kharfan-Dabaja MA, . Reduced-intensity transplantation for lymphomas using haploidentical related donors vs HLA-matched unrelated donors. Blood 2016;127:938947.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27.

    Ghosh N, Karmali R, Rocha V, . Reduced-intensity transplantation for lymphomas using haploidentical related donors versus HLA-matched sibling donors: a Center for International Blood and Marrow Transplant Research analysis. J Clin Oncol 2016;34:31413149.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28.

    Dehn J, Spellman S, Hurley CK, . Selection of unrelated donors and cord blood units for hematopoietic cell transplantation: guidelines from the NMDP/CIBMTR. Blood 2019;134:924934.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    Deeg HJ, Sandmaier B. Determining eligibility for allogeneic hematopoietic cell transplantation. Accessed November 5, 2019. Available at: https://www.uptodate.com/contents/determining-eligibility-for-allogeneic-hematopoietic-cell-transplantation/print

    • Export Citation
  • 30.

    Patient Eligibility for HCT. Accessed November 5, 2019. Available at: https://bethematchclinical.org/transplant-indications-and-outcomes/eligibility

  • 31.

    Sorror ML, Maris MB, Storb R, . Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood 2005;106:29122919.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32.

    Shouval R, Fein JA, Shouval A, . External validation and comparison of multiple prognostic scores in allogeneic hematopoietic stem cell transplantation. Blood Adv 2019;3:18811890.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33.

    McClune BL, Weisdorf DJ, Pedersen TL, . Effect of age on outcome of reduced-intensity hematopoietic cell transplantation for older patients with acute myeloid leukemia in first complete remission or with myelodysplastic syndrome. J Clin Oncol 2010;28:18781887.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34.

    Shah NN, Ahn KW, Litovich C, . Outcomes of Medicare-age eligible NHL patients receiving RIC allogeneic transplantation: a CIBMTR analysis. Blood Adv 2018;2:933940.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35.

    Muffly L, Pasquini MC, Martens M, . Increasing use of allogeneic hematopoietic cell transplantation in patients aged 70 years and older in the United States. Blood 2017;130:11561164.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36.

    Sorror M, Storer B, Sandmaier BM, . Hematopoietic cell transplantation-comorbidity index and Karnofsky performance status are independent predictors of morbidity and mortality after allogeneic nonmyeloablative hematopoietic cell transplantation. Cancer 2008;112:19922001.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37.

    Artz AS, Pollyea DA, Kocherginsky M, . Performance status and comorbidity predict transplant-related mortality after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 2006;12:954964.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38.

    Sayer HG, Kröger M, Beyer J, . Reduced intensity conditioning for allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia: disease status by marrow blasts is the strongest prognostic factor. Bone Marrow Transplant 2003;31:10891095.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39.

    Wildiers H, Heeren P, Puts M, . International Society of Geriatric Oncology consensus on geriatric assessment in older patients with cancer. J Clin Oncol 2014;32:25952603.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 40.

    Liu MA, DuMontier C, Murillo A, . Gait speed, grip strength, and clinical outcomes in older patients with hematologic malignancies. Blood 2019;134:374382.

  • 41.

    Abel GA, Klepin HD. Frailty and the management of hematologic malignancies. Blood 2018;131:515524.

  • 42.

    Mohile SG, Dale W, Somerfield MR, . Practical assessment and management of vulnerabilities in older patients receiving chemotherapy: ASCO guideline for geriatric oncology. J Clin Oncol 2018;36:23262347.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 43.

    Caveney J, Kanate AS, Hobbs G, Swisher A. Relationship of physical function to outcomes in autologous hematopoietic stem cell transplantation [abstract]. J Clin Oncol 2019;37(Suppl):Abstract 116.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 44.

    Derman BA, Kordas K, Ridgeway J, . Results from a multidisciplinary clinic guided by geriatric assessment before stem cell transplantation in older adults. Blood Adv 2019;3:34883498.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 45.

    Andorsky DJ, Loberiza FR, Lee SJ. Pre-transplantation physical and mental functioning is strongly associated with self-reported recovery from stem cell transplantation. Bone Marrow Transplant 2006;37:889895.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 46.

    Pillay B, Lee SJ, Katona L, . Psychosocial factors predicting survival after allogeneic stem cell transplant. Support Care Cancer 2014;22:25472555.

  • 47.

    Molassiotis A, van den Akker OBA, Boughton BJ. Perceived social support, family environment and psychosocial recovery in bone marrow transplant long-term survivors. Soc Sci Med 1997;44:317325.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 48.

    Meehan KR, Fitzmaurice T, Root L, . The financial requirements and time commitments of caregivers for autologous stem cell transplant recipients. J Support Oncol 2006;4:187190.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 49.

    Majhail NS, Omondi NA, Denzen E, . Access to hematopoietic cell transplantation in the United States. Biol Blood Marrow Transplant 2010;16:10701075.

  • 50.

    Baker KS, Davies SM, Majhail NS, . Race and socioeconomic status influence outcomes of unrelated donor hematopoietic cell transplantation. Biol Blood Marrow Transplant 2009;15:15431554.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 51.

    Hourigan CS, Dillon LW, Gui G, . Impact of conditioning intensity of allogeneic transplantation for acute myeloid leukemia with genomic evidence of residual disease [published online December 20, 2019]. J Clin Oncol, doi: 10.1200/JCO.19.03011

    • Search Google Scholar
    • Export Citation
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 702 702 463
PDF Downloads 256 256 168
EPUB Downloads 0 0 0