Blood Res.  2013 Sep;48(3):178-184. 10.5045/br.2013.48.3.178.

Allogeneic hematopoietic cell transplantation in adult patients with myelodysplastic/myeloproliferative neoplasms

• Lim SN
• Lee JH
• Lee JH
• Kim DY
• Kim SD
• Kang YA
• Lee YS
• Lee KH

• KMID: 2270703
• DOI: http://doi.org/10.5045/br.2013.48.3.178

Abstract

BACKGROUND
In adults, the 2 main types of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are chronic myelomonocytic leukemia (CMML) and atypical chronic myeloid leukemia (aCML). Both are associated with a poor prognosis. Allogeneic hematopoietic cell transplantation (HCT) is the only known curative treatment modality for these diseases, but data on outcomes following such treatment are limited. We analyzed the outcomes of patients with MDS/MPN after allogeneic HCT.
METHODS
This retrospective study included 10 patients with MDS/MPN who received allogeneic HCT at Asan Medical Center from 2002 to 2010. Of these 10 patients, 7 had CMML, 2 had aCML, and 1 had unclassifiable MDS/MPN. Five patients received a myeloablative conditioning (MAC) regimen (busulfan-cyclophosphamide), and 5 received reduced-intensity conditioning (RIC) regimen.
RESULTS
Neutrophil engraftment was achieved in all patients. After a median follow-up of 47.5 months among surviving patients, 4 had relapsed and 5 had died. There was only 1 treatment-related death. The 5-year rates of overall, relapse-free, and event-free survival were 42.2%, 51.9%, and 46.7%, respectively. Relapse was the leading cause of treatment failure, and all relapses were observed in patients who had received RIC and who did not develop chronic graft-versus-host disease.
CONCLUSION
Allogeneic HCT can induce durable remission in patients with MDS/MPN, but RIC cannot replace MAC in patients eligible for myeloablative treatments.

Keyword

MDS/MPN; Allogeneic HCT; Reduced-intensity; Relapse

MeSH Terms

Adult
Cell Transplantation
Disease-Free Survival
Follow-Up Studies
Humans
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
Leukemia, Myelomonocytic, Chronic
Neutrophils
Prognosis
Recurrence
Retrospective Studies
Transplants
Treatment Failure

Figure

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  Fig. 1 Survival differences between myeloablative conditioning and reduced-intensity conditioning; (A) overall survival, (B) relapse-free survival, (C) event-free survival.

Reference

1. Malcovati L, Cazzola M. Myelodysplastic/myeloproliferative disorders. Haematologica. 2008; 93:4–6. PMID: 18166777.

2. Orazi A, Germing U. The myelodysplastic/myeloproliferative neoplasms: myeloproliferative diseases with dysplastic features. Leukemia. 2008; 22:1308–1319. PMID: 18480833.

3. Vardiman JW, Harris NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood. 2002; 100:2292–2302. PMID: 12239137.

4. Vardiman JW, Thiele J, Arber DA, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009; 114:937–951. PMID: 19357394.

5. Germing U, Kundgen A, Gattermann N. Risk assessment in chronic myelomonocytic leukemia (CMML). Leuk Lymphoma. 2004; 45:1311–1318. PMID: 15359628.

6. Onida F, Kantarjian HM, Smith TL, et al. Prognostic factors and scoring systems in chronic myelomonocytic leukemia: a retrospective analysis of 213 patients. Blood. 2002; 99:840–849. PMID: 11806985.

7. Beran M, Kantarjian H, O'Brien S, et al. Topotecan, a topoisomerase I inhibitor, is active in the treatment of myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood. 1996; 88:2473–2479. PMID: 8839838.

8. Oki Y, Jelinek J, Shen L, Kantarjian HM, Issa JP. Induction of hypomethylation and molecular response after decitabine therapy in patients with chronic myelomonocytic leukemia. Blood. 2008; 111:2382–2384. PMID: 18055864.

9. Breccia M, Biondo F, Latagliata R, Carmosino I, Mandelli F, Alimena G. Identification of risk factors in atypical chronic myeloid leukemia. Haematologica. 2006; 91:1566–1568. PMID: 17043019.

10. Kurzrock R, Kantarjian HM, Shtalrid M, Gutterman JU, Talpaz M. Philadelphia chromosome-negative chronic myelogenous leukemia without breakpoint cluster region rearrangement: a chronic myeloid leukemia with a distinct clinical course. Blood. 1990; 75:445–452. PMID: 2403827.

11. Onida F, Ball G, Kantarjian HM, et al. Characteristics and outcome of patients with Philadelphia chromosome negative, bcr/abl negative chronic myelogenous leukemia. Cancer. 2002; 95:1673–1684. PMID: 12365015.

12. Elliott MA, Tefferi A, Hogan WJ, et al. Allogeneic stem cell transplantation and donor lymphocyte infusions for chronic myelomonocytic leukemia. Bone Marrow Transplant. 2006; 37:1003–1008. PMID: 16604096.

13. Kerbauy DM, Chyou F, Gooley T, et al. Allogeneic hematopoietic cell transplantation for chronic myelomonocytic leukemia. Biol Blood Marrow Transplant. 2005; 11:713–720. PMID: 16125642.

14. Koldehoff M, Beelen DW, Trenschel R, et al. Outcome of hematopoietic stem cell transplantation in patients with atypical chronic myeloid leukemia. Bone Marrow Transplant. 2004; 34:1047–1050. PMID: 15516946.

15. Mittal P, Saliba RM, Giralt SA, et al. Allogeneic transplantation: a therapeutic option for myelofibrosis, chronic myelomonocytic leukemia and Philadelphia-negative/BCR-ABL-negative chronic myelogenous leukemia. Bone Marrow Transplant. 2004; 33:1005–1009. PMID: 15048141.

16. Ocheni S, Kroger N, Zabelina T, Zander AR, Bacher U. Outcome of allo-SCT for chronic myelomonocytic leukemia. Bone Marrow Transplant. 2009; 43:659–661. PMID: 18997830.

17. Sorror ML, Maris MB, Storb R, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005; 106:2912–2919. PMID: 15994282.

18. Antin JH, Childs R, Filipovich AH, et al. Establishment of complete and mixed donor chimerism after allogeneic lymphohematopoietic transplantation: recommendations from a workshop at the 2001 Tandem Meetings of the International Bone Marrow Transplant Registry and the American Society of Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2001; 7:473–485. PMID: 11669214.

19. Przepiorka D, Weisdorf D, Martin P, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995; 15:825–828. PMID: 7581076.

20. Przepiorka D, Anderlini P, Saliba R, et al. Chronic graft-versus-host disease after allogeneic blood stem cell transplantation. Blood. 2001; 98:1695–1700. PMID: 11535499.

21. McDonald GB, Hinds MS, Fisher LD, et al. Veno-occlusive disease of the liver and multiorgan failure after bone marrow transplantation: a cohort study of 355 patients. Ann Intern Med. 1993; 118:255–267. PMID: 8420443.

22. Batsis I, Yannaki E, Kaloyannidis P, et al. Veno-occlusive disease prophylaxis with fresh frozen plasma and heparin in bone marrow transplantation. Thromb Res. 2006; 118:611–618. PMID: 16330084.

23. Kapaun P, Kabisch H, Held KR, Walter TA, Hegewisch S, Zander AR. Atypical chronic myelogenous leukemia in a patient with trisomy 8 mosaicism syndrome. Ann Hematol. 1993; 66:57–58. PMID: 8431524.

24. Lee JH, Lee JH, Lim SN, et al. Allogeneic hematopoietic cell transplantation for myelodysplastic syndrome: prognostic significance of pre-transplant IPSS score and comorbidity. Bone Marrow Transplant. 2010; 45:450–457. PMID: 19668236.

25. Alyea EP, Kim HT, Ho V, et al. Impact of conditioning regimen intensity on outcome of allogeneic hematopoietic cell transplantation for advanced acute myelogenous leukemia and myelodysplastic syndrome. Biol Blood Marrow Transplant. 2006; 12:1047–1055. PMID: 17067911.

26. Martino R, Iacobelli S, Brand R, et al. Retrospective comparison of reduced-intensity conditioning and conventional high-dose conditioning for allogeneic hematopoietic stem cell transplantation using HLA-identical sibling donors in myelodysplastic syndromes. Blood. 2006; 108:836–846. PMID: 16597592.

27. Laport GG, Sandmaier BM, Storer BE, et al. Reduced-intensity conditioning followed by allogeneic hematopoietic cell transplantation for adult patients with myelodysplastic syndrome and myeloproliferative disorders. Biol Blood Marrow Transplant. 2008; 14:246–255. PMID: 18215785.

28. Kroger N, Zabelina T, Guardiola P, et al. Allogeneic stem cell transplantation of adult chronic myelomonocytic leukaemia. A report on behalf of the Chronic Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT). Br J Haematol. 2002; 118:67–73. PMID: 12100129.

29. Lee JH, Choi SJ, Lee JH, et al. Anti-leukemic effect of graft-versus-host disease on bone marrow and extramedullary relapses in acute leukemia. Haematologica. 2005; 90:1380–1388. PMID: 16219575.

30. Weiden PL, Flournoy N, Thomas ED, et al. Antileukemic effect of graft-versus-host disease in human recipients of allogeneic-marrow grafts. N Engl J Med. 1979; 300:1068–1073. PMID: 34792.