Fludarabine-Melphalan Conditioning for AML and MDS: Alemtuzumab Reduces Acute and Chronic GVHD without Affecting Long-Term Outcomes

Biology of Blood and Marrow Transplantation

Volumn 15, Issue 5, 2009, Pages 610-617

  Besien, Koen Van ^a   Kunavakkam, Rangesh ^a   Rondon, Gaby ^b   De Lima, Marcos ^b   Artz, Andrew ^a   Oran, Betul ^b   Giralt, Sergio ^b  

^a UNIVERSITY OF CHICAGO   (United States)

^b UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

Author keywords

Alemtuzumab; Allogeneic transplant; AML; MDS; T cell depletion

Indexed keywords

ACICLOVIR; ALEMTUZUMAB; CYCLOSPORIN A; DIPHENHYDRAMINE; FLUDARABINE; GANCICLOVIR; GEMTUZUMAB OZOGAMICIN; GRANULOCYTE COLONY STIMULATING FACTOR; HYDROCORTISONE; MELPHALAN; METHOTREXATE; METHYLPREDNISOLONE; PARACETAMOL; TACROLIMUS; THYMOCYTE ANTIBODY; VALGANCICLOVIR;

ACUTE GRAFT VERSUS HOST DISEASE; ACUTE GRANULOCYTIC LEUKEMIA; ADOLESCENT; ADULT; ADVERSE DRUG REACTION; AGED; ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION; ARTICLE; CHILD; CHRONIC GRAFT VERSUS HOST DISEASE; CONTROLLED STUDY; CYTOMEGALOVIRUS INFECTION; DISEASE FREE SURVIVAL; DISEASE SEVERITY; DRUG BLOOD LEVEL; DRUG DOSE REDUCTION; DRUG MEGADOSE; GRAFT SURVIVAL; GRAFT VERSUS HOST REACTION; HUMAN; HUMAN CELL; LIVING DONOR; LOW DRUG DOSE; MAJOR CLINICAL STUDY; MYELODYSPLASTIC SYNDROME; OUTCOME ASSESSMENT; OVERALL SURVIVAL; REDUCED INTENSITY CONDITIONING; RELAPSE; UNSPECIFIED SIDE EFFECT;

ADOLESCENT; ADULT; AGED; ANTIBODIES, MONOCLONAL; ANTIBODIES, NEOPLASM; CHILD; FEMALE; GRAFT VS HOST DISEASE; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMANS; LEUKEMIA, MYELOID, ACUTE; MALE; MELPHALAN; MIDDLE AGED; MYELODYSPLASTIC SYNDROMES; TRANSPLANTATION CONDITIONING; TREATMENT OUTCOME; VIDARABINE PHOSPHATE; YOUNG ADULT;

EID: 63749116929     PISSN: 10838791     EISSN: 15236536     Source Type: Journal    
DOI: 10.1016/j.bbmt.2009.01.021     Document Type: Article

References (53)

1. van Besien K., Artz A., and Stock W. Unrelated donor transplantation over the age of 55. Are we merely getting (b)older?. Leukemia 19 (2005) 31-33
2. Shimoni A., Kroger N., Zabelina T., et al. Hematopoietic stem-cell transplantation from unrelated donors in elderly patients (age >55 years) with hematologic malignancies: older age is no longer a contraindication when using reduced intensity conditioning. Leukemia 19 (2005) 7-12
3. Wong R., Giralt S.A., Martin T., et al. Reduced-intensity conditioning for unrelated donor hematopoietic stem cell transplantation as treatment for myeloid malignancies in patients older than 55 years. Blood 102 (2003) 3052-3059
4. de Lima M., Anagnostopoulos A., Munsell M., et al. Non-ablative versus reduced intensity conditioning regimens in the treatment of acute myeloid leukemia and high-risk myelodysplastic syndrome. Dose is relevant for long-term disease control after allogeneic hematopoietic stem cell transplantation. Blood 104 (2004) 865-872
5. Giralt S., Cohen R., Mehra R., et al. Preliminary results of fludarabine/melphalan or 2CDA/melphalan as preparative regimens for allogeneic progenitor cell transplantation in poor candidates for myeloablative conditioning [abstract]. Blood 90 Suppl 1 (1997) 1853
6. van Besien K., Devine S., Wickrema A., et al. Fludarabine melphalan is a suitable alternative to fludarabine-TBI based conditioning for allogeneic transplantation in patients with advanced hematologic malignancies [abstract]. Hematol J 3 Suppl 1 (2002) 580
7. van Besien K., Devine S., Wickrema A., et al. Regimen-related toxicity after fludarabine-melphalan conditioning: a prospective study of 31 patients with hematologic malignancies. Bone Marrow Transplant 32 (2003) 471-476
8. Van Besien K.W., Demuynck H., LeMaistre C.F., Bogaerts M.A., and Champlin R.E. High dose melphalan allows durable engraftment of allogeneic bone marrow. Bone Marrow Transplant 15 (1995) 321-323
9. Singhal S., Powles R., Treleaven J., et al. Melphalan alone prior to allogeneic bone marrow transplantation from HLA-identical sibling donors for hematologic malignancies: alloengraftment with potential preservation of fertility in women. Bone Marrow Transplant 18 (1996) 1049-1055
10. Gandhi V., and Plunkett W. Cellular and clinical pharmacology of fludarabine. Clin Pharmacokinet 41 (2002) 93-103
11. Giralt S., Thall P.F., Khouri I., et al. Melphalan and purine analog-containing preparative regimens: reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation. Blood 97 (2001) 631-637
12. Oran B., Giralt S., Saliba R., et al. Allogeneic hematopoietic stem cell transplantation for the treatment of high-risk acute myelogenous leukemia and myelodysplastic syndrome using reduced-intensity conditioning with fludarabine and melphalan. Biol Blood Marrow Transplant 13 (2007) 454-462
13. van Besien K.W., Artz A., Smith S., et al. Fludarabine melphalan and alemtuzumab (Campath) conditioning for pts with high risk myeloid malignancies. High cure rate for pts with low leukemia burden. Blood 104 (2004) 2321
14. Morris E., Thomson K., Craddock C., et al. Outcome following alemtuzumab (CAMPATH-1H)-containing reduced intensity allogeneic transplant regimen for relapsed and refractory non-Hodgkin's lymphoma (NHL). Blood 104 (2004) 3865-3871
15. Chakraverty R., Peggs K., Chopra R., et al. Limiting transplantation-related mortality following unrelated donor stem cell transplantation by using a nonmyeloablative conditioning regimen. Blood 99 (2002) 1071-1078
16. Kottaridis P.D., Milligan D.W., Chopra R., et al. In vivo CAMPATH-1H prevents graft-versus-host disease following nonmyeloablative stem cell transplantation. Blood 96 (2000) 2419-2425
17. Tauro S., Craddock C., Peggs K., et al. Allogeneic stem-cell transplantation using a reduced-intensity conditioning regimen has the capacity to produce durable remissions and long-term disease-free survival in patients with high-risk acute myeloid leukemia and myelodysplasia. J Clin Oncol 23 (2005) 9387-9393
18. Avivi I., Chakrabarti S., Milligan D.W., et al. Incidence and outcome of adenovirus disease in transplant recipients after reduced-intensity conditioning with alemtuzumab. Biol Blood Marrow Transplant 10 (2004) 186-194
19. Chakrabarti S., Mackinnon S., Chopra R., et al. High incidence of cytomegalovirus infection after nonmyeloablative stem cell transplantation: potential role of Campath-1H in delaying immune reconstitution. Blood 99 (2002) 4357-4363
20. van Besien K., Artz A., Smith S., et al. Fludarabine, melphalan, and alemtuzumab conditioning in adults with standard-risk advanced acute myeloid leukemia and myelodysplastic syndrome. J Clin Oncol 23 (2005) 5728-5738
21. de Lima M., Champlin R.E., Thall P.F., et al. Phase I/II study of gemtuzumab ozogamicin added to fludarabine, melphalan and allogeneic hematopoietic stem cell transplantation for high-risk CD33 positive myeloid leukemias and myelodysplastic syndrome. Leukemia 22 (2008) 258-264
22. Kline J., Pollyea D.A., Stock W., et al. Pre-transplant ganciclovir and post transplant high-dose valacyclovir reduce CMV infections after alemtuzumab-based conditioning. Bone Marrow Transplant 37 (2006) 307-310
23. Przepiorka D., Weisdorf D., Martin P., et al. Consensus conference on GVHD grading. Bone Marrow Transplant 15 (1995) 825-828
24. van Besien K. Standardizing chronic graft-versus-host disease. Future Oncol 2 (2006) 459-462
25. Kaplan E.L., and Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 53 (1958) 457-481
26. Bartholomew A., Sher D., Sosler S., et al. Stem cell transplantation eliminates alloantibody in a highly sensitized patient. Transplant 72 (2001) 1653-1655
27. Gooley T.A., Leisenring W., Crowley J., and Storer B.E. Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med 18 (1999) 695-706
28. Chappell R. Letter to the editor. Int J Radiat Oncol Biol Phys 36 (1996) 988-989
29. Klein J.P., Rizzo J.D., Zhang M.J., and Keiding N. Statistical methods for the analysis and presentation of the results of bone marrow transplants. Part I: unadjusted analysis. Bone Marrow Transplant 28 (2001) 909-915
30. Sorror M.L., Giralt S., Sandmaier B.M., et al. Hematopoietic cell transplantation specific comorbidity index as an outcome predictor for patients with acute myeloid leukemia in first remission: combined FHCRC and MDACC experiences. Blood 110 (2007) 4606-4613
31. Bloomfield C.D., Lawrence D., Byrd J.C., et al. Frequency of prolonged remission duration after high-dose cytarabine intensification in acute myeloid leukemia varies by cytogenetic subtype. Cancer Res 58 (1998) 4173-4179
32. Flomenberg N., Baxter-Lowe L.A., Confer D., et al. Impact of HLA class I and class II high resolution matching on outcomes of unrelated donor bone marrow transplantation: HLA-C mismatching is associated with a strong adverse effect on transplant outcome. Blood 104 (2004) 1923-1930
33. Wingard J.R., and Leather H. A new era of antifungal therapy. Biol Blood Marrow Transplant 10 (2004) 73-90
34. Boeckh M., Nichols W.G., Papanicolaou G., et al. Cytomegalovirus in hematopoietic stem cell transplant recipients: current status, known challenges, and future strategies. Biol Blood Marrow Transplant 9 (2003) 543-558
35. Sorror M.L., Maris M.B., Storer B., et al. Comparing morbidity and mortality of HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative and myeloablative conditioning: influence of pretransplantation comorbidities. Blood 104 (2004) 961-968
36. Slavin S., Nagler A., Naparstek E., et al. 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 (1998) 756-763
37. Przepiorka D., Saliba R., Anderlini P., et al. Chronic graft vs host disease after allogeneic stem cell transplantation. Blood 98 (2001) 1695-1700
38. Ratzinger G., Reagan J.L., Heller G., Busam K.J., and Young J.W. Differential CD52 expression by distinct myeloid dendritic cell subsets: implications for alemtuzumab activity at the level of antigen presentation in allogeneic graft-host interactions in transplantation. Blood 101 (2003) 1422-1429
39. Klangsinsirikul P., Carter G.I., Byrne J.L., Hale G., and Russell N.H. Campath-1G causes rapid depletion of circulating host dendritic cells (DCs) before allogeneic transplantation but does not delay donor DC reconstitution. Blood 99 (2002) 2586-2591
40. Soiffer R. Immune modulation and chronic graft-versus-host disease. Bone Marrow Transplant 42 Suppl. 1 (2008) S66-S69
41. Deeg H.J., Appelbaum F.R., Storer B., et al. Reduced incidence of acute and chronic graft-versus-host disease (GvHD) without increased relapse in patients with high-risk myeloid disorders given thymoglobulin (THY) as part of the transplant conditioning regimen: a dose-finding study [abstract]. Blood 104 (2004) 181
42. Papadopoulos E.B., Carabasi M.H., Castro-Malaspina H., et al. T-cell-depleted allogeneic bone marrow transplantation as postremission therapy for acute myelogenous leukemia: freedom from relapse in the absence of graft-versus-host disease. Blood 91 (1998) 1083-1090
43. Soiffer R.J., Fairclough D., Robertson M., et al. CD6-depleted allogeneic bone marrow transplantation for acute leukemia in first complete remission. Blood 89 (1997) 3039-3047
44. Aversa F., Terenzi A., Carotti A., et al. Improved outcome with T-cell-depleted bone marrow transplantation for acute leukemia. J Clin Oncol 17 (1999) 1545-1550
45. Marks D.I., Bird J.M., Vettenranta K., et al. T cell-depleted unrelated donor bone marrow transplantation for acute myeloid leukemia. Biol Blood Marrow Transplant 6 (2000) 646-653
46. Chakrabarti S., and Marks D.I. Should we T cell deplete sibling grafts for acute myeloid leukaemia in first remission?. Bone Marrow Transplant 32 (2003) 1039-1050
47. Deeg H.J., Storer B.E., Boeckh M., et al. Reduced incidence of acute and chronic graft-versus-host disease with the addition of thymoglobulin to a targeted busulfan/cyclophosphamide regimen. Biol Blood Marrow Transplant 12 (2006) 573-584
48. Perez-Simon J.A., Kottaridis P.D., Martino R., et al. Nonmyeloablative transplantation with or without alemtuzumab: comparison between 2 prospective studies in patients with lymphoproliferative disorders. Blood 100 (2002) 3121-3127
49. Delgado J., Thomson K., Russell N., et al. Results of alemtuzumab-based reduced-intensity allogeneic transplantation for chronic lymphocytic leukemia: a British Society of Blood and Marrow Transplantation Study. Blood 107 (2006) 1724-1730
50. Crawley C., Szydlo R., Lalancette M., et al. Outcomes of reduced-intensity transplantation for chronic myeloid leukemia: an analysis of prognostic factors from the Chronic Leukemia Working Party of the EBMT. Blood 106 (2005) 2969-2976
51. Crawley C., Lalancette M., Szydlo R., et al. Outcomes for reduced-intensity allogeneic transplantation for multiple myeloma: an analysis of prognostic factors from the Chronic Leukaemia Working Party of the EBMT. Blood 105 (2005) 4532-4539
52. Bacigalupo A., Lamparelli T., Barisione G., et al. Thymoglobulin prevents chronic graft-versus-host disease, chronic lung dysfunction, and late transplant-related mortality: long-term follow-up of a randomized trial in patients undergoing unrelated donor transplantation. Biol Blood Marrow Transplant 12 (2006) 560-565
53. Wagner J.E., Thompson J.S., Carter S.L., and Kernan N.A. Effect of graft-versus-host disease prophylaxis on 3-year disease-free survival in recipients of unrelated donor bone marrow (T-cell Depletion Trial): a multi-centre, randomised phase II-III trial. Lancet 366 (2005) 733-741