Correspondence
Myelofibrosis with Myeloid Metaplasia
N Engl J Med 2000; 343:659-660August 31, 2000
- Article
To the Editor:
We would like to report additional data concerning the results of allogeneic stem-cell transplantation for myelofibrosis with myeloid metaplasia, which were recently summarized by Tefferi (April 27 issue).1 Since our initial report,2 we have collected data on 11 new patients and have obtained further follow-up information on the original 55 patients. In an analysis of the overall group of 66 patients, the neutrophil-recovery rate remains high, rising to 84 percent by day 30. In a multivariate analysis, factors that remain associated with delayed engraftment are a low dose of nucleated cells, the absence of a pretransplantation splenectomy, and osteomyelosclerosis. We now find, in addition, that a pretransplantation hemoglobin level of less than 10 g per deciliter is associated with delayed neutrophil engraftment (P=0.043), a finding that may explain why patients with severe anemia have a worse outcome. With regard to acute graft-versus-host disease, we confirm that osteomyelosclerosis is a risk factor for grade III or IV acute graft-versus-host disease (incidence, 40 percent vs. 13 percent; P=0.027). In addition, this analysis shows that total-body irradiation is associated with grade II to IV acute graft-versus-host disease. Finally, a new multivariate analysis shows the influence of the recipient's age on five-year overall survival (14 percent for patients ≥45 years old vs. 62 percent for those <45 years old; relative risk, 2.7; 95 percent confidence interval, 1.3 to 5.5; P<0.01). This finding should be taken into account when the timing of a transplantation is being considered, especially for patients at low to intermediate risk3,4 who are less than 40 years old, for whom planning a transplantation after the age of 45 years may not be the optimal strategy.
4 ReferencesPhilippe Guardiola, M.D.
Hôpital Saint-Louis, 75475 Paris CEDEX 10, FranceJeanne E. Anderson, M.D.
University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900Eliane Gluckman, M.D.
Hôpital Saint-Louis, 75475 Paris CEDEX 10, France1
Tefferi A . Myelofibrosis with myeloid metaplasia. N Engl J Med 2000;342:1255-1265
Full Text | Web of Science | Medline2
Guardiola P ,Anderson JE ,Bandini G , 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 Midollo Osseo, and Fred Hutchinson Cancer Research Center Collaborative Study. Blood 1999;93:2831-2838
Web of Science | Medline3
Dupriez B ,Morel P ,Demory JL , et al. Prognostic factors in agnogenic myeloid metaplasia: a report on 195 cases with a new scoring system. Blood 1996;88:1013-1018
Web of Science | Medline4
Cervantes F ,Barosi G ,Demory JL , et al. Myelofibrosis with myeloid metaplasia in young individuals: disease characteristics, prognostic factors and identification of risk groups. Br J Haematol 1998;102:684-690
CrossRef | Web of Science | Medline
To the Editor:
Tefferi's conclusion regarding the role of splenectomy in the management of myelofibrosis with myeloid metaplasia is based on a review of 223 patients in whom the surgery-related mortality and morbidity rates were 9 percent and 31 percent, respectively. Only half or fewer of the surviving patients had a durable benefit one year after splenectomy. These data are consistent with those of earlier reports1-4 and confirm that splenectomy in patients with myeloid metaplasia is a procedure of uncertain benefit and one that carries substantial risk.
Given the high surgery-related mortality associated with the procedure and its uncertain benefit, I am uncomfortable with the author's recommendation of splenectomy for patients with myeloid metaplasia and hydroxyurea-resistant symptomatic splenomegaly, overt portal hypertension, or progressive anemia that requires transfusion. It seems to me that the data presented by Tefferi suggest that splenectomy for myeloid metaplasia should be considered an experimental procedure that carries a prohibitive mortality.
4 ReferencesJ. Benbassat, M.D.
Brookdale Institute, Jerusalem 91130, Israel1
Schwartz SI ,Bernard RP ,Adams JT ,Bauman AW . Splenectomy for hematologic disorders. Arch Surg 1970;101:338-347
Web of Science | Medline2
Ward HP ,Block MH . The natural history of agnogenic myeloid metaplasia (AMM) and a critical evaluation of its relationship with the myeloproliferative syndrome. Medicine (Baltimore) 1971;50:357-420
Web of Science | Medline3
Coon WW ,Liepman MK . Splenectomy for agnogenic myeloid metaplasia. Surg Gynecol Obstet 1982;54:561-5634
Brenner B ,Nagler A ,Tatarsky I ,Hashmonai M . Splenectomy in agnogenic myeloid metaplasia and postpolycythemic myeloid metaplasia: a study of 34 cases. Arch Intern Med 1988;148:2501-2505
CrossRef | Web of Science | Medline
Author/Editor Response
Dr. Tefferi and a colleague reply:
To the Editor: The updated information on allogeneic hematopoietic stem-cell transplantation in myelofibrosis with myeloid metaplasia underscores the limited benefit of the procedure (five-year survival, 14 percent) in persons 45 years of age or older. The apparently better outcome in younger patients should be viewed in the context of two additional factors. First, the median survival in the subgroup of young patients with two or more favorable prognostic determinants (hemoglobin level, ≥10 g per deciliter; absence of constitutional symptoms; and <1 percent circulating blasts) may approach 15 years, and the risk of transplantation-related mortality and morbidity in these particular patients may not be justified.1 Second, the results of allogeneic stem-cell transplantation in young patients with unfavorable prognostic factors remain suboptimal (five-year survival, 31 to 43 percent)2 and some “successfully treated” patients may have a debilitating, chronic graft-versus-host disease. Nevertheless, current estimates of the benefits and risks are based on uncontrolled, retrospective data from a relatively small number of patients. Therefore, care must be taken in using current information when either recommending or discouraging the use of allogeneic stem-cell transplantation in an individual patient with myelofibrosis with myeloid metaplasia.
Benbassat and colleagues have previously expressed the need for a uniformly selected cohort of patients with myelofibrosis with myeloid metaplasia in whom the benefit of splenectomy may be accurately assessed.3 We believe that we have recently addressed this issue in a detailed account of our experience with 223 patients with myelofibrosis with myeloid metaplasia who underwent therapeutic splenectomy for a specified set of indications.4 We demonstrated that durable benefit was possible in the majority of patients who had a markedly compromised quality of life as a result of hypercatabolic symptoms or portal hypertension. The decision to perform splenectomy for transfusion-dependent anemia in patients with myelofibrosis with myeloid metaplasia (durable response, 23 percent) is facilitated by the fact that many of these patients may also have severe constitutional symptoms. We do realize that splenectomy in patients with myelofibrosis with myeloid metaplasia is associated with a substantial risk of surgery-related death (9 percent). However, the justification of risk in the use of palliative therapy is a complex issue that is often informally addressed in the context of the merits and inadequacies of alternative management. The decision-making process should always include the patient's preferences, which may override any other deliberation.
4 ReferencesAyalew Tefferi, M.D.
David M. Nagorney, M.D.
Mayo Clinic and Foundation, Rochester, MN 559051
Cervantes F ,Barosi G ,Demory JL , et al. Myelofibrosis with myeloid metaplasia in young individuals: disease characteristics, prognostic factors and identification of risk groups. Br J Haematol 1998;102:684-690
CrossRef | Web of Science | Medline2
Guardiola P ,Anderson JE ,Bandini G , 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 Midollo Osseo, and Fred Hutchinson Cancer Research Center Collaborative Study. Blood 1999;93:2831-2838
Web of Science | Medline3
Benbassat J ,Gilon D ,Penchas S . The choice between splenectomy and medical treatment in patients with advanced agnogenic myeloid metaplasia. Am J Hematol 1990;33:128-135
CrossRef | Web of Science | Medline4
Tefferi A ,Mesa RA ,Nagorney DM ,Schroeder G ,Silverstein MN . Splenectomy in myelofibrosis with myeloid metaplasia: a single-institution experience with 223 patients. Blood 2000;95:2226-2233
Web of Science | Medline
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A Bacigalupo, M Soraru, A Dominietto, S Pozzi, S Geroldi, M T Van Lint, A Ibatici, A M Raiola, F Frassoni, F De Stefano, S Verdiani, L Casarino, G Barosi. (2010) Allogeneic hemopoietic SCT for patients with primary myelofibrosis: a predictive transplant score based on transfusion requirement, spleen size and donor type. Bone Marrow Transplantation 45:3, 458-463
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Sergio Siragusa, Francesco Passamonti, Francisco Cervantes, Ayalew Tefferi. (2009) Survival in young patients with intermediate-/high-risk myelofibrosis: Estimates derived from databases for non transplant patients. American Journal of Hematology 84:3, 140-143
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Omar I. Abdel-Wahab, Ross L. Levine. (2009) Primary Myelofibrosis: Update on Definition, Pathogenesis, and Treatment. Annual Review of Medicine 60:1, 233-245
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N Kröger, R A Mesa. (2008) Choosing between stem cell therapy and drugs in myelofibrosis. Leukemia 22:3, 474-486
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Francisco Cervantes, Ruben Mesa, Giovanni Barosi. (2007) New and Old Treatment Modalities in Primary Myelofibrosis. The Cancer Journal 13:6, 377-383
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Francisco Cervantes. (2007) Myelofibrosis: biology and treatment options. European Journal of Haematology 79:s68, 13-17
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William J. Hogan, Mark R. Litzow, Ayalew Tefferi. (2007) Allogeneic hematopoietic cell transplantation in myelofibrosis with myeloid metaplasia. Current Hematologic Malignancy Reports 2:1, 34-42
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R. Hoffman, D. Rondelli. (2007) Biology and Treatment of Primary Myelofibrosis. Hematology 2007:1, 346-354
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S G Papageorgiou, A Castleton, A Bloor, P D Kottaridis. (2006) Allogeneic stem cell transplantation as treatment for myelofibrosis. Bone Marrow Transplantation 38:11, 721-727
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Giovanni Barosi, Andrea Bacigalupo. (2006) Allogeneic hematopoietic stem cell transplantation for myelofibrosis. Current Opinion in Hematology 13:2, 74-78
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A. Tefferi, T. Barbui. (2005) bcr/abl-Negative, Classic Myeloproliferative Disorders: Diagnosis and Treatment. Mayo Clinic Proceedings 80:9, 1220-1232
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Francisco Cervantes. (2005) Modern management of myelofibrosis. British Journal of Haematology 128:5, 583-592
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A. Tefferi, H. J. Deeg. (2004) Deciding on Transplantation for Myelofibrosis: Setting the Record Straight. Mayo Clinic Proceedings 79:7, 953-954
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Richard T. Maziarz, Ruben A. Mesa, Ayalew Tefferi. (2003) Allogeneic Stem Cell Transplantation for Chronic Myeloproliferative Disorders and Myelodysplastic Syndromes: The Question Is “When?”. Mayo Clinic Proceedings 78:8, 941-943
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R. T. Maziarz, R. A. Mesa, A. Tefferi. (2003) Allogeneic Stem Cell Transplantation for Chronic Myeloproliferative Disorders and Myelodysplastic Syndromes: The Question Is 'When?'. Mayo Clinic Proceedings 78:8, 941-943
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Deeg, H. Joachim, Appelbaum, Frederick R., . (2001) Stem-Cell Transplantation for Myelofibrosis. New England Journal of Medicine 344:10, 775-776
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