Single cord blood transplantation for acute myeloid leukemia patients aged 60 years or older: a retrospective study in Japan

Abstract

The availability of alternative donor sources could allow elderly patients to receive allogeneic hematopoietic cell transplantation (HCT). We retrospectively evaluated the outcomes of single-unit cord blood transplantation (CBT) in 1577 patients aged ≥60 years with acute myeloid leukemia (AML) in Japan between 2002 and 2017. In total, 990 (63%) patients were not in complete remission (CR) at the time of CBT. A myeloablative conditioning regimen (52%) and calcineurin inhibitor (CI) + mycophenolate mofetil (MMF)–based graft-versus-host disease (GVHD) prophylaxis (45%) were more commonly used. With a median follow-up for survivors of 31 months, the probability of overall survival and the cumulative incidence of leukemia-related mortality at 3 years was 31% and 29%, respectively. The cumulative incidence of non-relapse mortality (NRM) at 100 days and 3 years were 24% and 41%, respectively. The cumulative incidences of grade II–IV and grade III–IV acute GVHD at 100 days and extensive chronic GVHD at 2 years were 44%, 16%, and 14%, respectively. The cumulative incidence of neutrophil engraftment was 80% at 42 days. Results of multivariate analysis indicated that the following factors were significantly associated with higher overall mortality: performance status ≥1, hematopoietic cell transplantation-specific comorbidity index ≥3, adverse cytogenetics, extramedullary disease at diagnosis, and non-CR status at CBT. By contrast, female sex, HLA disparities ≥2, mycophenolate mofetil–based GVHD prophylaxis, and recent CBT were significantly associated with lower overall mortality. In conclusion, single CBT offers a curative option for AML patients aged ≥60 years with careful patient selection.

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Data availability

Data were obtained from the Transplant Registry Unified Management Program (TRUMP) of the Japanese Data Center for Hematopoietic Cell Transplantation (JDCHCT). TRUMP is covering almost all (>300) HCT centers in Japan. Researchers can apply for data access with TRUMP and must have their study protocol approved by the JDCHCT.

References

  1. 1.

    Juliusson G, Antunovic P, Derolf A, Lehmann S, Möllgård L, Stockelberg D, Tidefelt U, Wahlin A, Höglund M (2009) Age and acute myeloid leukemia: real world data on decision to treat and outcomes from the Swedish Acute Leukemia Registry. Blood. 113:4179–4187

    CAS  PubMed  Article  Google Scholar 

  2. 2.

    Juliusson G, Lazarevic V, Hörstedt AS, Hagberg O, Höglund M (2012) Acute myeloid leukemia in the real world: why population-based registries are needed. Blood. 119:3890–3899

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  3. 3.

    Oran B, Weisdorf DJ (2012) Survival for older patients with acute myeloid leukemia: a population-based study. Haematologica. 97:1916–1924

    PubMed  PubMed Central  Article  Google Scholar 

  4. 4.

    Appelbaum FR, Gundacker H, Head DR, Slovak ML, Willman CL, Godwin JE, Anderson JE, Petersdorf SH (2006) Age and acute myeloid leukemia. Blood. 107:3481–3485

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  5. 5.

    Yanada M, Naoe T (2012) Acute myeloid leukemia in older adults. Int J Hematol. 96:186–193

    PubMed  Article  Google Scholar 

  6. 6.

    Hahn T, McCarthy PL Jr, Zhang MJ et al (2008) Risk factors for acute graft-versus-host disease after human leukocyte antigen-identical sibling transplants for adults with leukemia. J Clin Oncol. 26:5728–5734

    PubMed  PubMed Central  Article  Google Scholar 

  7. 7.

    Jagasia M, Arora M, Flowers ME et al (2012) Risk factors for acute GVHD and survival after hematopoietic cell transplantation. Blood. 119:296–307

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  8. 8.

    Flowers ME, Inamoto Y, Carpenter PA et al (2011) Comparative analysis of risk factors for acute graft-versus-host disease and for chronic graft-versus-host disease according to National Institutes of Health consensus criteria. Blood. 117:3214–3219

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  9. 9.

    Eapen M, Rocha V, Sanz G, Scaradavou A, Zhang MJ, Arcese W, Sirvent A, Champlin RE, Chao N, Gee AP, Isola L, Laughlin MJ, Marks DI, Nabhan S, Ruggeri A, Soiffer R, Horowitz MM, Gluckman E, Wagner JE, Center for International Blood and Marrow Transplant Research, Acute Leukemia Working Party Eurocord (the European Group for Blood Marrow Transplantation), National Cord Blood Program of the New York Blood Center (2010) Effect of graft source on unrelated donor haemopoietic stem-cell transplantation in adults with acute leukaemia: a retrospective analysis. Lancet Oncol. 11:653–660

    PubMed  PubMed Central  Article  Google Scholar 

  10. 10.

    Terakura S, Atsuta Y, Tsukada N, Kobayashi T, Tanaka M, Kanda J, Najima Y, Fukuda T, Uchida N, Takahashi S, Nagamura-Inoue T, Morishima Y, Miyamura K (2016) Comparison of outcomes of 8/8 and 7/8 allele-matched unrelated bone marrow transplantation and single-unit cord blood transplantation in adults with acute leukemia. Biol Blood Marrow Transplant. 22:330–338

    PubMed  Article  Google Scholar 

  11. 11.

    Milano F, Gooley T, Wood B, Woolfrey A, Flowers ME, Doney K, Witherspoon R, Mielcarek M, Deeg JH, Sorror M, Dahlberg A, Sandmaier BM, Salit R, Petersdorf E, Appelbaum FR, Delaney C (2016) Cord-blood transplantation in patients with minimal residual disease. N Engl J Med. 375:944–953

    PubMed  PubMed Central  Article  Google Scholar 

  12. 12.

    Konuma T, Tsukada N, Kanda J, Uchida N, Ohno Y, Miyakoshi S, Kanamori H, Hidaka M, Sakura T, Onizuka M, Kobayashi N, Sawa M, Eto T, Matsuhashi Y, Kato K, Ichinohe T, Atsuta Y, Miyamura K, Donor/Source Working Group of the Japan Society for Hematopoietic Cell Transplantation (2016) Comparison of transplant outcomes from matched sibling bone marrow or peripheral blood stem cell and unrelated cord blood in patients 50 years or older. Am J Hematol. 91:E284–E292

    PubMed  Article  Google Scholar 

  13. 13.

    Shouval R, Fein JA, Labopin M, Kröger N, Duarte RF, Bader P, Chabannon C, Kuball J, Basak GW, Dufour C, Galimard JE, Polge E, Lankester A, Montoto S, Snowden JA, Styczynski J, Yakoub-Agha I, Mohty M, Nagler A (2019) Outcomes of allogeneic haematopoietic stem cell transplantation from HLA-matched and alternative donors: a European Society for Blood and Marrow Transplantation registry retrospective analysis. Lancet Haematol. 6:e573–e584

    PubMed  Article  Google Scholar 

  14. 14.

    Uchida N, Wake A, Takagi S, Yamamoto H, Kato D, Matsuhashi Y, Matsumura T, Seo S, Matsuno N, Masuoka K, Kusumi E, Yuji K, Miyakoshi S, Matsuzaki M, Yoneyama A, Taniguchi S (2008) Umbilical cord blood transplantation after reduced-intensity conditioning for elderly patients with hematologic diseases. Biol Blood Marrow Transplant. 14:583–590

    PubMed  Article  Google Scholar 

  15. 15.

    Majhail NS, Brunstein CG, Shanley R, Sandhu K, McClune B, Oran B, Warlick ED, Wagner JE, Weisdorf DJ (2012) Reduced-intensity hematopoietic cell transplantation in older patients with AML/MDS: umbilical cord blood is a feasible option for patients without HLA-matched sibling donors. Bone Marrow Transplant. 47:494–498

    CAS  PubMed  Article  Google Scholar 

  16. 16.

    Weisdorf D, Eapen M, Ruggeri A, Zhang MJ, Zhong X, Brunstein C, Ustun C, Rocha V, Gluckman E (2014) Alternative donor transplantation for older patients with acute myeloid leukemia in first complete remission: a center for international blood and marrow transplant research-eurocord analysis. Biol Blood Marrow Transplant. 20:816–822

    PubMed  PubMed Central  Article  Google Scholar 

  17. 17.

    Sandhu KS, Brunstein C, DeFor T, Bejanyan N, Arora M, Warlick E, Weisdorf D, Ustun C (2016) Umbilical cord blood transplantation outcomes in acute myelogenous leukemia/myelodysplastic syndrome patients aged ≥70 years. Biol Blood Marrow Transplant. 22:390–393

    PubMed  Article  Google Scholar 

  18. 18.

    Muffly L, Pasquini MC, Martens M, Brazauskas R, Zhu X, Adekola K, Aljurf M, Ballen KK, Bajel A, Baron F, Battiwalla M, Beitinjaneh A, Cahn JY, Carabasi M, Chen YB, Chhabra S, Ciurea S, Copelan E, D’Souza A, Edwards J, Foran J, Freytes CO, Fung HC, Gale RP, Giralt S, Hashmi SK, Hildebrandt GC, Ho V, Jakubowski A, Lazarus H, Luskin MR, Martino R, Maziarz R, McCarthy P, Nishihori T, Olin R, Olsson RF, Pawarode A, Peres E, Rezvani AR, Rizzieri D, Savani BN, Schouten HC, Sabloff M, Seftel M, Seo S, Sorror ML, Szer J, Wirk BM, Wood WA, Artz A (2017) Increasing use of allogeneic hematopoietic cell transplantation in patients aged 70 years and older in the United States. Blood. 130:1156–1164

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  19. 19.

    Konuma T, Kato S, Isobe M, Mizusawa M, Oiwa-Monna M, Takahashi S, Tojo A (2019) Reduced-toxicity myeloablative conditioning consisting of fludarabine/busulfan/low-dose total body irradiation/granulocyte colony-stimulating factor-combined cytarabine in single cord blood transplantation for elderly patients with nonremission myeloid malignancies. Biol Blood Marrow Transplant. 25:764–770

    CAS  PubMed  Article  Google Scholar 

  20. 20.

    Ohta T, Sugio Y, Imanaga H, Oku S, Ohno Y (2019) Conditioning regimen with a 75% dose of standard busulfan/cyclophosphamide plus fludarabine before cord blood transplantation in older patients with AML and MDS. Int J Hematol. 110:347–354

    PubMed  Article  Google Scholar 

  21. 21.

    Atsuta Y, Suzuki R, Yoshimi A, Gondo H, Tanaka J, Hiraoka A, Kato K, Tabuchi K, Tsuchida M, Morishima Y, Mitamura M, Kawa K, Kato S, Nagamura T, Takanashi M, Kodera Y (2007) Unification of hematopoietic stem cell transplantation registries in Japan and establishment of the TRUMP System. Int J Hematol. 86:269–274

    PubMed  Article  Google Scholar 

  22. 22.

    Atsuta Y (2016) Introduction of Transplant Registry Unified Management Program 2 (TRUMP2): scripts for TRUMP data analyses, part I (variables other than HLA-related data). Int J Hematol. 103:3–10

    PubMed  Article  Google Scholar 

  23. 23.

    Kanda J (2016) Scripts for TRUMP data analyses. Part II (HLA-related data): statistical analyses specific for hematopoietic stem cell transplantation. Int J Hematol. 103:11–19

    CAS  PubMed  Article  Google Scholar 

  24. 24.

    Nakagawa R, Watanabe T, Kawano Y, Kanai S, Suzuya H, Kaneko M, Watanabe H, Okamoto Y, Kuroda Y, Nakayama T, the Chugoku-Shikoku Cord Blood Bank (2004) Analysis of maternal and neonatal factors that influence the nucleated and CD34+ cell yield for cord blood banking. Transfusion. 44:262–267

    PubMed  Article  Google Scholar 

  25. 25.

    Takanashi M, Oba A, Ogawa A, Ito M, Kawahata Y, Nakajima K (2010) Red blood cell depletion of cord blood using an automated system -evaluation of the AXP system. Japanese Journal of Transfusion and Cell Therapy. 56:62–67

    Article  Google Scholar 

  26. 26.

    Yanada M, Konuma T, Kuwatsuka Y, Kondo T, Kawata T, Takahashi S, Uchida N, Miyakoshi S, Tanaka M, Ozawa Y, Sawa M, Nakamae H, Aotsuka N, Kanda J, Takanashi M, Kanda Y, Atsuta Y, Yano S (2019) Unit selection for umbilical cord blood transplantation for adults with acute myeloid leukemia in complete remission: a Japanese experience. Bone Marrow Transplant. 54:1789–1798

    CAS  PubMed  Article  Google Scholar 

  27. 27.

    Atsuta Y, Kanda J, Takanashi M, Morishima Y, Taniguchi S, Takahashi S, Ogawa H, Ohashi K, Ohno Y, Onishi Y, Aotsuka N, Nagamura-Inoue T, Kato K, Kanda Y, on behalf of the HLA Working Group of the Japan Society for Hematopoietic Cell Transplantation (2013) Different effects of HLA disparity on transplant outcomes after single-unit cord blood transplantation between pediatric and adult patients with leukemia. Haematologica. 98:814–822

    PubMed  PubMed Central  Article  Google Scholar 

  28. 28.

    Przepiorka D, Weisdorf D, Martin P et al (1995) 1994 Consensus conference on acute GVHD grading. Bone Marrow Transplant. 15:825–828

    CAS  PubMed  Google Scholar 

  29. 29.

    Sullivan KM, Agura E, Anasetti C, Appelbaum F, Badger C, Bearman S, Erickson K, Flowers M, Hansen J, Loughran T (1991) Chronic graft-versus-host disease and other late complications of bone marrow transplantation. Semin Hematol. 28:250–259

    CAS  PubMed  Google Scholar 

  30. 30.

    Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP (1982) Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 5:649–655

    CAS  PubMed  Article  Google Scholar 

  31. 31.

    Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, Storer B (2005) Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 106:2912–2919

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  32. 32.

    Yanada M, Mori J, Aoki J, Harada K, Mizuno S, Uchida N, Kurosawa S, Toya T, Kanamori H, Ozawa Y, Ogawa H, Henzan H, Iwato K, Sakura T, Ota S, Fukuda T, Ichinohe T, Atsuta Y, Yano S (2018) Effect of cytogenetic risk status on outcomes for patients with acute myeloid leukemia undergoing various types of allogeneic hematopoietic cell transplantation: an analysis of 7812 patients. Leuk Lymphoma. 59:601–609

    PubMed  Article  Google Scholar 

  33. 33.

    Giralt S, Ballen K, Rizzo D, Bacigalupo A, Horowitz M, Pasquini M, Sandmaier B (2009) Reduced-intensity conditioning regimen workshop: defining the dose spectrum. Report of a workshop convened by the center for international blood and marrow transplant research. Biol Blood Marrow Transplant. 15:367–369

    PubMed  PubMed Central  Article  Google Scholar 

  34. 34.

    Kanda Y (2013) Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 48:452–458

    CAS  PubMed  Article  Google Scholar 

  35. 35.

    Yamamoto H, Uchida N, Yuasa M, Kageyama K, Ota H, Kaji D, Nishida A, Ishiwata K, Takagi S, Tsuji M, Asano-Mori Y, Yamamoto G, Izutsu K, Masuoka K, Wake A, Yoneyama A, Makino S, Taniguchi S (2016) A novel reduced-toxicity myeloablative conditioning regimen using full-dose busulfan, fludarabine, and melphalan for single cord blood transplantation provides durable engraftment and remission in nonremission myeloid malignancies. Biol Blood Marrow Transplant. 22:1844–1850

    CAS  PubMed  Article  Google Scholar 

  36. 36.

    Lim Z, Brand R, Martino R, van Biezen A, Finke J, Bacigalupo A, Beelen D, Devergie A, Alessandrino E, Willemze R, Ruutu T, Boogaerts M, Falda M, Jouet JP, Niederwieser D, Kroger N, Mufti GJ, de Witte TM (2010) Allogeneic hematopoietic stem-cell transplantation for patients 50 years or older with myelodysplastic syndromes or secondary acute myeloid leukemia. J Clin Oncol. 28:405–411

    PubMed  Article  Google Scholar 

  37. 37.

    McClune BL, Weisdorf DJ, Pedersen TL et al (2010) 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. 28:1878–1887

    PubMed  PubMed Central  Article  Google Scholar 

  38. 38.

    Aoki J, Kanamori H, Tanaka MY et al (2016) Impact of age on outcomes of allogeneic hematopoietic stem cell transplantation with reduced intensity conditioning in elderly patients with acute myeloid leukemia. Am J Hematol 91:302–307

    PubMed  Article  Google Scholar 

  39. 39.

    Koreth J, Aldridge J, Kim HT, Alyea EP III, Cutler C, Armand P, Ritz J, Antin JH, Soiffer RJ, Ho VT (2010) Reduced-intensity conditioning hematopoietic stem cell transplantation in patients over 60 years: hematologic malignancy outcomes are not impaired in advanced age. Biol Blood Marrow Transplant. 16:792–800

    PubMed  PubMed Central  Article  Google Scholar 

  40. 40.

    Farag SS, Maharry K, Zhang MJ, Pérez WS, George SL, Mrózek K, DiPersio J, Bunjes DW, Marcucci G, Baer MR, Cairo M, Copelan E, Cutler CS, Isola L, Lazarus HM, Litzow MR, Marks DI, Ringdén O, Rizzieri DA, Soiffer R, Larson RA, Tallman MS, Bloomfield CD, Weisdorf DJ, Acute Leukemia Committee of the Center for International Blood and Marrow Transplant Research and Cancer and Leukemia Group B (2011) Comparison of reduced-intensity hematopoietic cell transplantation with chemotherapy in patients age 60-70 years with acute myelogenous leukemia in first remission. Biol Blood Marrow Transplant. 17:1796–1803

    PubMed  Article  Google Scholar 

  41. 41.

    Chevallier P, Szydlo RM, Blaise D, Tabrizi R, Michallet M, Uzunov M, Fegueux N, Guilhot F, Lapusan S, Gratecos N, Cahn JY, Socié G, Yakoub-Agha I, Huynh A, Francois S, Bay JO, Maury S, Buzyn A, Contentin N, Mohty M (2012) Reduced-intensity conditioning before allogeneic hematopoietic stem cell transplantation in patients over 60 years: a report from the SFGM-TC. Biol Blood Marrow Transplant. 18:289–294

    PubMed  Article  Google Scholar 

  42. 42.

    Brunner AM, Kim HT, Coughlin E, Alyea EP III, Armand P, Ballen KK, Cutler C, Dey BR, Glotzbecker B, Koreth J, McAfee SL, Spitzer TR, Soiffer RJ, Antin JH, Ho VT, Chen YB (2013) Outcomes in patients age 70 or older undergoing allogeneic hematopoietic stem cell transplantation for hematologic malignancies. Biol Blood Marrow Transplant. 19:1374–1380

    PubMed  Article  Google Scholar 

  43. 43.

    Devine SM, Owzar K, Blum W et al (2015) Phase II study of allogeneic transplantation for older patients with acute myeloid leukemia in first complete remission using a reduced-intensity conditioning regimen: results from Cancer and Leukemia Group B 100103 (Alliance for Clinical Trials in Oncology)/Blood and Marrow Transplant Clinical Trial Network 0502. J Clin Oncol. 33:4167–4175

    PubMed  PubMed Central  Article  Google Scholar 

  44. 44.

    Rashidi A, Ebadi M, Colditz GA, DiPersio JF (2016) Outcomes of allogeneic stem cell transplantation in elderly patients with acute myeloid leukemia: a systematic review and meta-analysis. Biol Blood Marrow Transplant. 22:651–657

    PubMed  Article  Google Scholar 

  45. 45.

    Poiré X, Labopin M, Polge E, Passweg J, Craddock C, Blaise D, Cornelissen JJ, Volin L, Russell NH, Socié G, Michallet M, Fegueux N, Chevallier P, Brecht A, Hunault-Berger M, Mohty M, Esteve J, Nagler A (2018) Allogeneic stem cell transplantation benefits for patients ≥ 60 years with acute myeloid leukemia and FLT3 internal tandem duplication: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Haematologica. 103:256–265

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  46. 46.

    Rashidi A, DiPersio JF, Westervelt P et al (2016) Do adults aged 70 years or older with acute myeloid leukemia benefit from allogeneic hematopoietic cell transplantation? Leukemia. 30:1797–1799

    CAS  PubMed  Article  Google Scholar 

  47. 47.

    Santoro N, Labopin M, Giannotti F, Ehninger G, Niederwieser D, Brecht A, Stelljes M, Kröger N, Einsele H, Eder M, Hallek M, Glass B, Finke J, Ciceri F, Mohty M, Ruggeri A, Nagler A (2018) Unmanipulated haploidentical in comparison with matched unrelated donor stem cell transplantation in patients 60 years and older with acute myeloid leukemia: a comparative study on behalf of the ALWP of the EBMT. J Hematol Oncol. 11:55

    PubMed  PubMed Central  Article  Google Scholar 

  48. 48.

    Ustun C, Le-Rademacher J, Wang HL et al (2019) Allogeneic hematopoietic cell transplantation compared to chemotherapy consolidation in older acute myeloid leukemia (AML) patients 60-75 years in first complete remission (CR1): an alliance (A151509), SWOG, ECOG-ACRIN, and CIBMTR study. Leukemia. 33:2599–2609

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  49. 49.

    Ringdén O, Boumendil A, Labopin M, Canaani J, Beelen D, Ehninger G, Niederwieser D, Finke J, Stelljes M, Gerbitz A, Ganser A, Kröger N, Kantz L, Brecht A, Savani B, Sadeghi B, Mohty M, Nagler A (2019) Outcome of allogeneic hematopoietic stem cell transplantation in patients age >69 years with acute myelogenous leukemia: on behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 25:1975–1983

    PubMed  Article  Google Scholar 

  50. 50.

    Muffly LS, Boulukos M, Swanson K, Kocherginsky M, Cerro, Schroeder L, Pape L, Extermann M, van Besien K, Artz AS (2013) Pilot study of comprehensive geriatric assessment (CGA) in allogeneic transplant: CGA captures a high prevalence of vulnerabilities in older transplant recipients. Biol Blood Marrow Transplant. 19:429–434

  51. 51.

    Rodrigues M, de Souza PMR (2020) de Oliveira Muniz Koch L, et al. The use of comprehensive geriatric assessment in older patients before allologeneic hematopoietic stem cell transplantation: a cross-sectional study. J Geriatr Oncol. 11:100–106

    PubMed  Article  Google Scholar 

  52. 52.

    Muffly LS, Kocherginsky M, Stock W, Chu Q, Bishop MR, Godley LA, Kline J, Liu H, Odenike OM, Larson RA, van Besien K, Artz AS (2014) Geriatric assessment to predict survival in older allogeneic hematopoietic cell transplantation recipients. Haematologica. 99:1373–1379

    PubMed  PubMed Central  Article  Google Scholar 

  53. 53.

    Deschler B, Ihorst G, Schnitzler S, Bertz H, Finke J (2018) Geriatric assessment and quality of life in older patients considered for allogeneic hematopoietic cell transplantation: a prospective risk factor and serial assessment analysis. Bone Marrow Transplant. 53:565–575

    CAS  PubMed  Article  Google Scholar 

  54. 54.

    Huang LW, Sheng Y, Andreadis C, Logan AC, Mannis GN, Smith CC, Gaensler KML, Martin TG, Damon LE, Steinman MA, Huang CY, Olin RL (2020) Functional status as measured by geriatric assessment predicts inferior survival in older allogeneic hematopoietic cell transplantation recipients. Biol Blood Marrow Transplant. 26:189–196

    PubMed  Article  Google Scholar 

  55. 55.

    Jayani R, Rosko A, Olin R, Artz A (2020) Use of geriatric assessment in hematopoietic cell transplant. J Geriatr Oncol. 11:225–236

    PubMed  Article  Google Scholar 

  56. 56.

    Konuma T, Kanda J, Inamoto Y et al (2019) Improvement of early mortality in single-unit cord blood transplantation for Japanese adults from 1998 to 2017. Am J Hematol. 95:343–353

    Google Scholar 

  57. 57.

    Lazaryan A, Weisdorf DJ, DeFor T, Brunstein CG, MacMillan ML, Bejanyan N, Holtan S, Blazar BR, Wagner JE, Arora M (2016) Risk factors for acute and chronic graft-versus-host disease after allogeneic hematopoietic cell transplantation with umbilical cord blood and matched sibling donors. Biol Blood Marrow Transplant. 22:134–140

    PubMed  Article  Google Scholar 

  58. 58.

    Sanz J, Jaramillo FJ, Planelles D, Montesinos P, Lorenzo I, Moscardó F, Martin G, López F, Martínez J, Jarque I, de la Rubia J, Larrea L, Sanz MA, Sanz GF (2014) Impact on outcomes of human leukocyte antigen matching by allele-level typing in adults with acute myeloid leukemia undergoing umbilical cord blood transplantation. Biol Blood Marrow Transplant. 20:106–110

    CAS  PubMed  Article  Google Scholar 

  59. 59.

    Cunha R, Loiseau P, Ruggeri A, Sanz G, Michel G, PaolaIori A, Socié G, Arcese W, Picardi A, Dias de Heredia C, Rio B, Locatelli F, O'Brien TA, Yakoub-Agha I, Angel Diaz M, Milpied N, Bittencourt H, Pedro Souza M, Aljurf M, Charron D, Boudjedir K, Labopin M, Gluckman E, Rocha V (2014) Impact of HLA mismatch direction on outcomes after umbilical cord blood transplantation for hematological malignant disorders: a retrospective Eurocord-EBMT analysis. Bone Marrow Transplant. 49:24–29

    CAS  PubMed  Article  Google Scholar 

  60. 60.

    Konuma T, Kato S, Ishii H, Takeda R, Oiwa-Monna M, Tojo A, Takahashi S (2015) HLA-DRB1 mismatch is associated with a decreased relapse in adult acute myeloid leukemia after single-unit myeloablative cord blood transplantation. Ann Hematol. 94:1233–1235

    PubMed  Article  Google Scholar 

  61. 61.

    Yabe T, Azuma F, Kashiwase K et al (2018) HLA-DPB1 mismatch induces a graft-versus-leukemia effect without severe acute GVHD after single-unit umbilical cord blood transplantation. Leukemia. 32:168–175

    CAS  PubMed  Article  Google Scholar 

  62. 62.

    Terakura S, Kuwatsuka Y, Yamasaki S et al (2017) GvHD prophylaxis after single-unit reduced intensity conditioning cord blood transplantation in adults with acute leukemia. Bone Marrow Transplant. 52:1261–1267

    CAS  PubMed  Article  Google Scholar 

  63. 63.

    Terakura S, Wake A, Inamoto Y et al (2017) Exploratory research for optimal GvHD prophylaxis after single unit CBT in adults: short-term methotrexate reduced the incidence of severe GvHD more than mycophenolate mofetil. Bone Marrow Transplant. 52:423–430

    CAS  PubMed  Article  Google Scholar 

  64. 64.

    Murata M, Nakasone H, Kanda J, Nakane T, Furukawa T, Fukuda T, Mori T, Taniguchi S, Eto T, Ohashi K, Hino M, Inoue M, Ogawa H, Atsuta Y, Nagamura-Inoue T, Yabe H, Morishima Y, Sakamaki H, Suzuki R (2013) Clinical factors predicting the response of acute graft-versus-host disease to corticosteroid therapy: an analysis from the GVHD Working Group of the Japan Society for Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant. 19:1183–1189

    CAS  PubMed  Article  Google Scholar 

  65. 65.

    Newell LF, Flowers ME, Gooley TA et al (2013) Characteristics of chronic GVHD after cord blood transplantation. Bone Marrow Transplant. 48:1285–1290

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  66. 66.

    Foster LW, McLellan L, Rybicki L, Dabney J, Copelan E, Bolwell B (2013) Validating the positive impact of in-hospital lay care-partner support on patient survival in allogeneic BMT: a prospective study. Bone Marrow Transplant. 48:671–677

    CAS  PubMed  Article  Google Scholar 

  67. 67.

    Papaemmanuil E, Gerstung M, Bullinger L, Gaidzik VI, Paschka P, Roberts ND, Potter NE, Heuser M, Thol F, Bolli N, Gundem G, van Loo P, Martincorena I, Ganly P, Mudie L, McLaren S, O’Meara S, Raine K, Jones DR, Teague JW, Butler AP, Greaves MF, Ganser A, Döhner K, Schlenk RF, Döhner H, Campbell PJ (2016) Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med. 374:2209–2221

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  68. 68.

    Molica M, Breccia M, Foa R, Jabbour E, Kadia TM (2019) Maintenance therapy in AML: the past, the present and the future. Am J Hematol. 94:1254–1265

    PubMed  Article  Google Scholar 

  69. 69.

    Frisch A, Rowe JM, Ofran Y (2020; In press) How we treat older patients with acute myeloid leukaemia. Br J Haematol. 191:682–691

    PubMed  Article  Google Scholar 

Download references

Acknowledgements

The authors thank all of the physicians and staff at the hospital and the cord blood banks who provided the clinical data to the Transplant Registry Unified Management Program of the Japanese Data Center for Hematopoietic Cell Transplantation.

Funding

This work was supported in part by the Practical Research Project for Allergic Diseases and Immunology (Research Technology of Medical Transplantation) from Japan Agency for Medical Research and Development, AMED under grant 18ek0510023h0002.

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M.I. analyzed the data, performed the statistical analysis, and wrote the first draft of the manuscript. T. Konuma designed the research, analyzed the data, performed the statistical analysis, and wrote the first draft of the manuscript. M.M. and M.Y. contributed to the critical review of the manuscript. All the other authors contributed to data collection. All authors approved the final version.

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Correspondence to Takaaki Konuma.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Because of the retrospective nature of this analysis and the use of de-identified patient data, informed consent was not obtained from all individual participants included in this study.

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The authors declare no competing interests.

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Isobe, M., Konuma, T., Masuko, M. et al. Single cord blood transplantation for acute myeloid leukemia patients aged 60 years or older: a retrospective study in Japan. Ann Hematol (2021). https://doi.org/10.1007/s00277-021-04464-5

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Keywords

  • Allogeneic hematopoietic cell transplantation
  • Cord blood transplantation
  • Acute myeloid leukemia
  • Elderly
  • Older patients