Haploidentical hematopoietic cell transplantation using in vitro T cell depleted grafts as salvage therapy in patients with disease relapse after prior allogeneic transplantation
Disease relapse after one or more allogeneic hematopoietic cell transplantations (HCT) represents a therapeutic challenge with all options bearing a significant morbidity and mortality. Haploidentical HCT may induce more pronounced anti-leukemic effects and was evaluated at our center in 25 consecutive patients with disease relapse after preceding HCT receiving haploidentical grafts after in vitro T cell depletion. Overall survival at 1 and 2 years was 32 and 14%, respectively. Of note, patients with complete remission (CR) before haploidentical HCT had a very favorable overall survival of 41.7% at 2 years. Cumulative incidence of non-relapse mortality was 36 and 40% at 1 and 2 years, respectively. With a cumulative incidence for relapse of 36 and 45.6% at 1 and 2 years, disease-free survival (DFS) was 28 and 14.4%, respectively. Here also, patients with CR before haploidentical HCT had a favorable DFS of 42% at 2 years. Only very limited acute (11 patients (44%) with a median grade 1) and chronic graft versus host disease (GvHD) (5 patients (11%), limited grade only) was observed. The main complications and causes of death comprised—besides relapse—infections and bleeding complications. Hence, haploidentical HCT can achieve long-term survival comparable to second transplantation with matched or mismatched donors for patients with otherwise deleterious prognosis and should be considered as a treatment option for patients experiencing disease relapse after previous allogeneic HCT.
KeywordsHaploidentical hematopoietic cell transplantation Relapse Graft versus host disease Salvage therapy
The authors wish to thank Mirjam Breig, Anja Junker, and Diana Kilian for assistance in data collection and database maintenance. We would also like to thank the staff of the stem cell laboratory of the University Hospital of Tübingen, especially Stefanie Ackermann and Gabriele Hochwelker. Moreover, the authors wish to thank the physicians and nursing staff of the transplantation ward and the outpatient clinic for participating in patient care, and Prof. Dr. Peter Martus (Institute for clinical Epidemiology and applied Biometry, University Tuebingen) for statistical advice.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest to disclose.
Sebastian Haen was supported by the German José Carreras Leukemia Foundation (Project-No. DJS 08-04). Part of this work has been supported by an institutional grant (AKF 151-0-0) of the University of Tuebingen.
Research involving human participants
This retrospective analysis was reviewed and approved by the institutional ethics committee of the medical faculty and university hospital Tübingen.
Due to the retrospective nature of this analysis, no informed content was obtained from the patients.
- 1.Messori A, Bosi A, Bacci S, Laszlo D et al (1999) Retrospective survival analysis and cost-effectiveness evaluation of second allogeneic bone marrow transplantation in patients with acute leukemia. Gruppo Italiano Trapianto di Midollo Osseo. Bone Marrow Transplant 23:489–495CrossRefPubMedGoogle Scholar
- 2.Porter DL, Alyea EP, Antin JH, DeLima M et al (2010) NCI first international workshop on the biology, prevention, and treatment of relapse after allogeneic hematopoietic stem cell transplantation: report from the committee on treatment of relapse after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 16:1467–1503CrossRefPubMedPubMedCentralGoogle Scholar
- 6.Michallet M, Tanguy ML, Socie G, Thiebaut A et al (2000) Second allogeneic haematopoietic stem cell transplantation in relapsed acute and chronic leukaemias for patients who underwent a first allogeneic bone marrow transplantation: a survey of the Societe Francaise de Greffe de moelle (SFGM). Br J Haematol 108:400–407CrossRefPubMedGoogle Scholar
- 10.de Lima M, Porter DL, Battiwalla M, Bishop MR et al (2014) Proceedings from the National Cancer Institute’s second international workshop on the biology, prevention, and treatment of relapse after hematopoietic stem cell transplantation: part III. Prevention and treatment of relapse after allogeneic transplantation. Biol Blood Marrow Transplant 20:4–13CrossRefPubMedGoogle Scholar
- 13.Huang XJ, Zhu HH, Chang YJ, Xu LP et al (2012) The superiority of haploidentical related stem cell transplantation over chemotherapy alone as postremission treatment for patients with intermediate- or high-risk acute myeloid leukemia in first complete remission. Blood 119:5584–5590CrossRefPubMedGoogle Scholar
- 14.Kanda J, Long GD, Gasparetto C, Horwitz ME et al. (2013) Reduced-intensity allogeneic transplantation using alemtuzumab from HLA-matched related, unrelated, or haploidentical related donors for patients with hematologic malignancies. Biol Blood Marrow TransplantGoogle Scholar
- 15.Gao L, Wen Q, Chen X, Liu Y et al (2014) Effects of priming with recombinant human granulocyte colony-stimulating factor on conditioning regimen for high-risk acute myeloid leukemia patients undergoing human leukocyte antigen-haploidentical hematopoietic stem cell transplantation: a multicenter randomized controlled study in Southwest China. Biol Blood Marrow Transplant 20:1932–1939CrossRefPubMedGoogle Scholar
- 25.Slavin S, Nagler A, Naparstek E, Kapelushnik Y et al (1998) Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood 91:756–763PubMedGoogle Scholar