Pilot study of reduced‐intensity conditioning followed by allogeneic stem cell transplantation from related and unrelated donors in patients with myelofibrosis

A prospective pilot study was performed to evaluate the effect of reduced‐intensity conditioning with busulphan (10 mg/kg), fludarabine (180 mg/qm) and anti‐thymocyte globulin followed by allogeneic stem cell transplantation from related (n = 8) and unrelated donors (n = 13) in 21 patients with myelofibrosis. The median age of the patients was 53 years (range, 32–63). No primary graft failure occurred. The median time until leucocyte (>1·0 × 109/l) and platelet (>20 × 109/l) engraftment was 16 (range, 11–26) and 23 d (range, 9–139) respectively. Complete donor chimaerism on day 100 was seen in 20 patients (95%). Acute graft‐versus‐host disease (GvHD) grades II–IV and III/IV occurred in 48% and 19% of cases and 55% of the patients had chronic GvHD. Treatment‐related mortality was 0% at day 100 and 16% [95% confidence interval (CI): 0–32%] at 1 year. Haematological response was seen in 100% and complete histopathological remission was observed in 75% of the patients and 25% of the patients showed partial histopathological remission with a continuing decline in the grade of fibrosis. After a median follow‐up of 22 months (range, 4–59), the 3‐year estimated overall and disease‐free survival was 84% (95% CI: 67–100%).

[1]  R. Hoffman,et al.  Allogeneic hsct with reduced intensity conditioning regimens in high risk patients with myelofibrosis , 2004 .

[2]  H. Deeg,et al.  Allogeneic hematopoietic stem cell transplantation for myelofibrosis. , 2003, Blood.

[3]  V. Diehl,et al.  Bone marrow histopathology following cytoreductive therapy in chronic idiopathic myelofibrosis , 2003, Histopathology.

[4]  N. Kröger,et al.  ATG as part of the conditioning regimen reduces transplant-related mortality (TRM) and improves overall survival after unrelated stem cell transplantation in patients with chronic myelogenous leukemia (CML) , 2003, Bone Marrow Transplantation.

[5]  W Hasegawa,et al.  Stem cell transplantation for myelofibrosis: a report from two Canadian centers , 2003, Bone Marrow Transplantation.

[6]  N. Kröger,et al.  Dose‐reduced conditioning regimen followed by allogeneic stem cell transplantation in patients with myelofibrosis with myeloid metaplasia , 2002, British journal of haematology.

[7]  V. Diehl,et al.  Follow‐up examinations including sequential bone marrow biopsies in essential thrombocythemia (ET): A retrospective clinicopathological study of 120 patients , 2002, American journal of hematology.

[8]  A. Verma,et al.  Allogeneic blood cell transplantation following reduced-intensity conditioning is effective therapy for older patients with myelofibrosis with myeloid metaplasia. , 2002, Blood.

[9]  N. Kröger,et al.  Real-time quantitative Y chromosome-specific PCR (QYCS-PCR) for monitoring hematopoietic chimerism after sex-mismatched allogeneic stem cell transplantation. , 2001, Journal of hematotherapy & stem cell research.

[10]  J. Radich,et al.  Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. , 2001, Blood.

[11]  A. Nagler,et al.  Low-intensity conditioning is sufficient to ensure engraftment in matched unrelated bone marrow transplantation. , 2001, Experimental hematology.

[12]  N. Kröger,et al.  Anti-Thymocyte-Globulin as part of the preparative regimen prevents graft failure and severe Graft versus Host disease (GvHD) in allogeneic stem cell transplantation from unrelated donors , 2001, Annals of Hematology.

[13]  P. Thall,et al.  Melphalan and purine analog-containing preparative regimens: reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation. , 2001, Blood.

[14]  E. Montserrat,et al.  Complete remission of idiopathic myelofibrosis following donor lymphocyte infusion after failure of allogeneic transplantation: demonstration of a graft-versus-myelofibrosis effect , 2000, Bone Marrow Transplantation.

[15]  Russell,et al.  Induction of remission after donor leucocyte infusion for the treatment of relapsed chronic idiopathic myelofibrosis following allogeneic transplantation: evidence for a ‘graft vs. myelofibrosis’ effect , 2000, British journal of haematology.

[16]  H. Deeg,et al.  Allogeneic stem cell transplantation for agnogenic myeloid metaplasia: a European Group for Blood and Marrow Transplantation, Société Française de Greffe de Moelle, Gruppo Italiano per il Trapianto del Midollo Osseo, and Fred Hutchinson Cancer Research Center Collaborative Study. , 1999, Blood.

[17]  P. Wollan,et al.  Population‐based incidence and survival figures in essential thrombocythemia and agnogenic myeloid metaplasia: An Olmsted county study, 1976–1995 , 1999, American journal of hematology.

[18]  J Crowley,et al.  Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. , 1999, Statistics in medicine.

[19]  G. Barosi,et al.  The Italian Consensus Conference on Diagnostic Criteria for Myelofibrosis with Myeloid Metaplasia , 1999, British journal of haematology.

[20]  V. Diehl,et al.  Prognostic impact of apoptosis and proliferation in idiopathic (primary) myelofibrosis , 1999, Annals of Hematology.

[21]  E. Montserrat,et al.  Myelofibrosis with myeloid metaplasia in young indidviduals: disease characteristics, prognostic factors and identification of risk groups , 1998, British journal of haematology.

[22]  A. Nagler,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. , 1998, Blood.

[23]  R. Fischer,et al.  Prognostic factors in idiopathic (Primary) osteomyelofibrosis , 1997, Cancer.

[24]  P. Morel,et al.  Prognostic factors in agnogenic myeloid metaplasia: a report on 195 cases with a new scoring system. , 1996, Blood.

[25]  E D Thomas,et al.  1994 Consensus Conference on Acute GVHD Grading. , 1995, Bone marrow transplantation.

[26]  Y. Najean,et al.  The very‐long‐term course of polycythaemia: a complement to the previously published data of the Polycythaemia Vera Study Group , 1994, British journal of haematology.

[27]  G. McDonald,et al.  Veno-occlusive Disease of the Liver and Multiorgan Failure after Bone Marrow Transplantation: A Cohort Study of 355 Patients , 1993, Annals of Internal Medicine.

[28]  S. Pileri,et al.  Myelofibrosis with myeloid metaplasia: clinical and haematological parameters predicting survival in a series of 133 patients , 1990, British journal of haematology.

[29]  P. Fenaux,et al.  PROGNOSTIC CLASSIFICATION OF MYELOFIBROSIS WITH MYELOID METAPLASIA , 1989, British journal of haematology.

[30]  F. Appelbaum,et al.  Regimen-related toxicity in patients undergoing bone marrow transplantation. , 1988, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[31]  R. Berger,et al.  Essential thrombocythemias. Clinical evolutionary and biological data , 1986, Cancer.

[32]  T. Pearson,et al.  Treatment of primary proliferative polycythaemia by venesection and low dose busulphan: retrospective study from one centre , 1985, British journal of haematology.

[33]  A. Manoharan,et al.  The Reticulin Content of Bone Marrow in Acute Leukaemia in Adults , 1979, British journal of haematology.

[34]  D. Bauermeister.  Quantitation of bone marrow reticulin--a normal range. , 1971, American journal of clinical pathology.

[35]  M. Goudemand,et al.  [Essential thrombocythemias]. , 1957, La semaine des hopitaux : organe fonde par l'Association d'enseignement medical des hopitaux de Paris.