eMedicine Specialties > Hematology > Stem Cells and Disorders

Agnogenic Myeloid Metaplasia With Myelofibrosis: Follow-up

Author: Asheesh Lal, MBBS, MD, Physician, Department of Internal Medicine, Lexington Medical Center
Contributor Information and Disclosures

Updated: Oct 8, 2008

Follow-up

Complications

  • Portal hypertension occurs in approximately 7% of patients with agnogenic myeloid metaplasia and may be related to increased portal flow resulting from marked splenomegaly and to intrahepatic obstruction resulting from thrombotic obliteration of small portal veins. This may result in variceal bleeding or ascites. Hepatic or portal vein thrombosis may occur. Symptomatic portal hypertension is managed by splenectomy, with or without the creation of a portosystemic shunt.
  • Splenic infarction may occur and results in an acute or subacute onset of severe pain in the left upper quadrant that may be associated with nausea, fever, and referred left shoulder discomfort. The episode is usually self-limited and may last several days. Treat patients with hydration and opiate analgesics. Individuals with refractory cases of agnogenic myeloid metaplasia may require splenectomy or splenic irradiation.
  • Extramedullary hematopoiesis may involve any organ, and symptoms depend on the organ or site of involvement. Extramedullary hematopoiesis may result in GI tract bleeding, spinal cord compression, seizures, hemoptysis, and/or effusions. These are easily controlled with low-dose radiation.
  • Patients with agnogenic myeloid metaplasia are also prone to developing infectious complications because of defects in humoral immunity.
  • Osteosclerosis, hypertrophic osteoarthropathy, and periostitis may occur, resulting in significant pain and discomfort. This may require the administration of nonsteroidal anti-inflammatory drugs or opioid analgesics.
  • Gout or urate stones may develop as a result of uric acid overproduction. Allopurinol should be used to keep uric acid in the reference range.

Prognosis

  • The median length of survival for patients with agnogenic myeloid metaplasia is 3.5-5.5 years. The 5-year survival rate is about half of that expected for age- and sex-matched controls. Less than 20% of patients are expected to be alive at 10 years. The common causes of death in those with agnogenic myeloid metaplasia are infections, hemorrhage, cardiac failure, postsplenectomy mortality, and leukemic transformation.
  • Advanced age and anemia are associated with shorter survival.
  • Other poor prognostic factors of agnogenic myeloid metaplasia include the presence of hypercatabolic symptoms, leukocytosis (leukocyte count, 10,000-30,000/μL), leukopenia, circulating blasts, increased numbers of granulocyte precursors, thrombocytopenia (platelet count, <100,000/μL), and karyotype abnormalities.
  • A simple scoring system to determine the prognosis in agnogenic myeloid metaplasia has been proposed.29 This system uses 2 adverse prognostic factors: a hemoglobin value less than 10 g/dL and a total WBC count less than 4000/μL or greater than 30,000/μL. Patients with no risk factors are at low risk, those with both the risk factors are at high risk, and those with a single risk factor are at intermediate risk. Median survival times for low-risk groups are 93 months; intermediate-risk groups, 26 months; and high-risk groups, 13 months.
  • Low-risk patients with an abnormal karyotype have a worse outcome than those with a normal karyotype (median survival, 50 mo vs 112 mo).
  • Leukocytosis (>30,000/μL) and abnormal karyotype have reportedly been associated with increased risk of transformation to AML.
  • Bone marrow vascularity is significantly increased in patients with agnogenic myeloid metaplasia. Increased bone marrow microvascular density has also been reported in approximately 70% of patients with agnogenic myeloid metaplasia, and it is an independent poor prognostic factor for survival.

Miscellaneous

Medicolegal Pitfalls

  • A diagnosis of agnogenic myeloid metaplasia must be carefully considered, especially in patients with other malignancies or granulomatous disorders. These patients may have findings of marrow fibrosis as observed in agnogenic myeloid metaplasia. A misdiagnosis of agnogenic myeloid metaplasia in a patient with a potentially curable disorder could result in a lawsuit. Performing testing for bcr:abl gene rearrangements is important to exclude CML.
  • Patients with agnogenic myeloid metaplasia who require a splenectomy should be well counseled regarding the risks and benefits of the procedure. Splenectomy has been associated with a significant risk of perioperative mortality and complications. Careful preoperative counseling may help avoid legal problems.
 


More on Agnogenic Myeloid Metaplasia With Myelofibrosis

Overview: Agnogenic Myeloid Metaplasia With Myelofibrosis
Differential Diagnoses & Workup: Agnogenic Myeloid Metaplasia With Myelofibrosis
Treatment & Medication: Agnogenic Myeloid Metaplasia With Myelofibrosis
Follow-up: Agnogenic Myeloid Metaplasia With Myelofibrosis
Multimedia: Agnogenic Myeloid Metaplasia With Myelofibrosis
References
Further Reading
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References

  1. Heuck G. Zwei Falle von Leukemie mit eigenthumlichen Blutresp. Knockenmarksbefund. Arch Pathol Anat Physiol Virchows. 1879;78:475-96.

  2. Barosi G. Myelofibrosis with myeloid metaplasia: diagnostic definition and prognostic classification for clinical studies and treatment guidelines. J Clin Oncol. Sep 1999;17(9):2954-70. [Medline].

  3. Vallespí T, Imbert M, Mecucci C, Preudhomme C, Fenaux P. Diagnosis, classification, and cytogenetics of myelodysplastic syndromes. Haematologica. Mar 1998;83(3):258-75. [Medline]. [Full Text].

  4. Jacobson RJ, Salo A, Fialkow PJ. Agnogenic myeloid metaplasia: a clonal proliferation of hematopoietic stem cells with secondary myelofibrosis. Blood. Feb 1978;51(2):189-94. [Medline]. [Full Text].

  5. Tefferi A, Thiele J, Orazi A, et al. Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel. Blood. Aug 15 2007;110(4):1092-7. [Medline]. [Full Text].

  6. Mesa RA, Silverstein MN, Jacobsen SJ, Wollan PC, Tefferi A. Population-based incidence and survival figures in essential thrombocythemia and agnogenic myeloid metaplasia: an Olmsted County Study, 1976-1995. Am J Hematol. May 1999;61(1):10-5. [Medline]. [Full Text].

  7. Honda Y, Delzell E, Cole P. An updated study of mortality among workers at a petroleum manufacturing plant. J Occup Environ Med. Feb 1995;37(2):194-200. [Medline].

  8. Hu H. Benzene-associated myelofibrosis [letter]. Ann Intern Med. Jan 1987;106(1):171-2. [Medline].

  9. Visfeldt J, Andersson M. Pathoanatomical aspects of malignant haematological disorders among Danish patients exposed to thorium dioxide. APMIS. Jan 1995;103(1):29-36. [Medline].

  10. Aksoy M, Erdem S, Dincol G. Two rare complications of chronic benzene poisoning: myeloid metaplasia and paroxysmal nocturnal hemoglobinuria. Report of two cases. Blut. Apr 1975;30(4):255-60. [Medline].

  11. Levine RL, Belisle C, Wadleigh M, et al. X-inactivation-based clonality analysis and quantitative JAK2V617F assessment reveal a strong association between clonality and JAK2V617F in PV but not ET/MMM, and identifies a subset of JAK2V617F-negative ET and MMM patients with clonal hematopoiesis. Blood. May 15 2006;107(10):4139-41. [Medline]. [Full Text].

  12. Baxter EJ, Scott LM, Campbell PJ, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. Mar 19-25 2005;365(9464):1054-61. [Medline].

  13. Barosi G, Marchetti M, Massa M et al. Incidence and clinical profile of JAK2 V617F mutation in myelofibrosis with myeloid metaplasia [abstract]. Blood. November 2005;106:a256. [Full Text].

  14. Gilbert HS. Long term treatment of myeloproliferative disease with interferon-alpha-2b: feasibility and efficacy. Cancer. Sep 15 1998;83(6):1205-13. [Medline]. [Full Text].

  15. Koeffler HP, Cline MJ, Golde DW. Splenic irradiation in myelofibrosis: effect on circulating myeloid progenitor cells. Br J Haematol. Sep 1979;43(1):69-77. [Medline].

  16. Mesa RA, Steensma DP, Pardanani A, et al. A phase 2 trial of combination low-dose thalidomide and prednisone for the treatment of myelofibrosis with myeloid metaplasia. Blood. Apr 1 2003;101(7):2534-41. [Medline]. [Full Text].

  17. Merup M, Kutti J, Birgergård G, et al. Negligible clinical effects of thalidomide in patients with myelofibrosis with myeloid metaplasia. Med Oncol. 2002;19(2):79-86. [Medline].

  18. Elliott MA, Mesa RA, Li CY, et al. Thalidomide treatment in myelofibrosis with myeloid metaplasia. Br J Haematol. May 2002;117(2):288-96. [Medline].

  19. Odenike O, Hoving K, Sher D, et al. Phase II study of imatinib mesylate (IM) in myelofibrosis with myeloid metaplasia (MMM) [abstract]. Proc Am Soc Clin Oncol. 2003;22:a2354.

  20. Pozzato G, Zorat F, Nascimben F, et al. Thalidomide therapy in compensated and decompensated myelofibrosis with myeloid metaplasia. Haematologica. Jul 2001;86(7):772-3. [Medline]. [Full Text].

  21. Canepa L, Ballerini F, Varaldo R, et al. Thalidomide in agnogenic and secondary myelofibrosis. Br J Haematol. Nov 2001;115(2):313-5. [Medline].

  22. Barosi G, Grossi A, Comotti B, et al. Safety and efficacy of thalidomide in patients with myelofibrosis with myeloid metaplasia. Br J Haematol. Jul 2001;114(1):78-83. [Medline].

  23. Tefferi A, Elliot MA. Serious myeloproliferative reactions associated with the use of thalidomide in myelofibrosis with myeloid metaplasia [letter]. Blood. Dec 1 2000;96(12):4007. [Medline]. [Full Text].

  24. Tefferi A, Cortes J, Verstovsek S, et al. Lenalidomide therapy in myelofibrosis with myeloid metaplasia. Blood. Aug 15 2006;108(4):1158-64. [Medline]. [Full Text].

  25. Mesa RA, Tefferi A, Gray LA, et al. In vitro antiproliferative activity of the farnesyltransferase inhibitor R115777 in hematopoietic progenitors from patients with myelofibrosis with myeloid metaplasia. Leukemia. May 2003;17(5):849-55. [Medline]. [Full Text].

  26. Cortes J, Albitar M, Thomas D, et al. Efficacy of the farnesyl transferase inhibitor R115777 in chronic myeloid leukemia and other hematologic malignancies. Blood. Mar 1 2003;101(5):1692-7. [Medline]. [Full Text].

  27. Giles FJ, List AF, Carroll M, et al. PTK787/ZK 222584, a small molecule tyrosine kinase receptor inhibitor of vascular endothelial growth factor (VEGF), has modest activity in myelofibrosis with myeloid metaplasia. Leuk Res. Jul 2007;31(7):891-7. [Medline].

  28. Giles FJ, Cooper MA, Silverman L, et al. Phase II study of SU5416--a small-molecule, vascular endothelial growth factor tyrosine-kinase receptor inhibitor--in patients with refractory myeloproliferative diseases. Cancer. Apr 15 2003;97(8):1920-8. [Medline]. [Full Text].

  29. 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. Aug 1 1996;88(3):1013-8. [Medline]. [Full Text].

  30. Barosi G, Ambrosetti A, Centra A, et al, and the Italian Cooperative Study Group on Myeloid with Myeloid Metaplasia. Splenectomy and risk of blast transformation in myelofibrosis with myeloid metaplasia. Blood. May 15 1998;91(10):3630-6. [Medline]. [Full Text].

  31. Bartlett RP, Greipp PR, Tefferi A, et al. Extramedullary hematopoiesis manifesting as a symptomatic pleural effusion. Mayo Clin Proc. Dec 1995;70(12):1161-4. [Medline].

  32. Besa EC, Nowell PC, Geller NL, Gardner FH. Analysis of the androgen response of 23 patients with agnogenic myeloid metaplasia: the value of chromosomal studies in predicting response and survival. Cancer. Jan 15 1982;49(2):308-13. [Medline].

  33. Castro-Malaspina H, Rabellino EM, Yen A, Nachman RL, Moore MA. Human megakaryocyte stimulation of proliferation of bone marrow fibroblasts. Blood. Apr 1981;57(4):781-7. [Medline]. [Full Text].

  34. 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. Aug 1998;102(3):684-90. [Medline].

  35. Cortes J, Giles F, O'Brien S, et al. Results of imatinib mesylate therapy in patients with refractory or recurrent acute myeloid leukemia, high-risk myelodysplastic syndrome, and myeloproliferative disorders. Cancer. Jun 1 2003;97(11):2760-6. [Medline]. [Full Text].

  36. Di Raimondo F, Azzaro MP, Palumbo GA, et al. Elevated vascular endothelial growth factor (VEGF) serum levels in idiopathic myelofibrosis. Leukemia. Jun 2001;15(6):976-80. [Medline].

  37. Giovanni B, Michelle E, Letizia C, et al. Thalidomide in myelofibrosis with myeloid metaplasia: a pooled-analysis of individual patient data from five studies. Leuk Lymphoma. Dec 2002;43(12):2301-7. [Medline].

  38. Gisslinger H, Gisslinger B, Kees M, et al. Imatinib mesylate in chronic idiopathic myelofibrosis, a Phase II trial [abstract]. Blood. 2002;100:800a.

  39. 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 del Midollo Osseo, and Fred Hutchinson Cancer Research Center Collaborative Study. Blood. May 1 1999;93(9):2831-8. [Medline]. [Full Text].

  40. Guardiola P, Esperou H, Cazals-Hatem D, et al. Allogeneic bone marrow transplantation for agnogenic myeloid metaplasia. French Society of Bone Marrow Transplantation. Br J Haematol. Sep 1997;98(4):1004-9. [Medline].

  41. Hasselbalch HC. Myelofibrosis with myeloid metaplasia: the advanced phase of an untreated disseminated hematological cancer. Time to change our therapeutic attitude with early upfront treatment?. Leuk Res. Jul 15 2008;epub ahead of print. [Medline].

  42. Hasselblach HC, Bjerrum OW, Jensen BA, Hansen PB, Birgens H. STI571 (Gleevec) therapy in idiopathic and postpolycythemic myelofibrosis [abstract]. Blood. 2002;100:344b.

  43. Ho AYL, Lim S, Fishlock K, et al. Imatinib mesylate in myelofibrosis: preliminary results show early sustained improvements in platelet counts and splenomegaly [abstract]. Blood. 2002;100:799a.

  44. Jaroch MT, Broughan TA, Hermann RE. The natural history of splenic infarction. Surgery. Oct 1986;100(4):743-50. [Medline].

  45. Kimura A, Katoh O, Hyodo H, Kuramoto A. Transforming growth factor-beta regulates growth as well as collagen and fibronectin synthesis of human marrow fibroblasts. Br J Haematol. Aug 1989;72(4):486-91. [Medline].

  46. Kvasnicka HM, Thiele J, Werden C, et al. Prognostic factors in idiopathic (primary) osteomyelofibrosis. Cancer. Aug 15 1997;80(4):708-19. [Medline]. [Full Text].

  47. Lévy V, Bourgarit A, Delmer A, et al. Treatment of agnogenic myeloid metaplasia with danazol: a report of four cases. Am J Hematol. Dec 1996;53(4):239-41. [Medline].

  48. McNally RJ, Rowland D, Roman E, Cartwright RA. Age and sex distributions of hematological malignancies in the U.K. Hematol Oncol. Nov 1997;15(4):173-89. [Medline].

  49. Mesa RA, Hanson CA, Rajkumar SV, Schroeder G, Tefferi A. Evaluation and clinical correlations of bone marrow angiogenesis in myelofibrosis with myeloid metaplasia. Blood. Nov 15 2000;96(10):3374-80. [Medline]. [Full Text].

  50. Miller JB, Testa JR, Lindgren V, Rowley JD. The pattern and clinical significance of karyotypic abnormalities in patients with idiopathic and postpolycythemic myelofibrosis. Cancer. Feb 1 1985;55(3):582-91. [Medline].

  51. Piccaluga PP, Visani G, Pileri SA, et al. Clinical efficacy and antiangiogenic activity of thalidomide in myelofibrosis with myeloid metaplasia. A pilot study. Leukemia. Sep 2002;16(9):1609-14. [Medline]. [Full Text].

  52. Rameshwar P, Denny TN, Stein D, Gascón P. Monocyte adhesion in patients with bone marrow fibrosis is required for the production of fibrogenic cytokines. Potential role for interleukin-1 and TGF-beta. J Immunol. Sep 15 1994;153(6):2819-30. [Medline].

  53. Rodríguez JN, Martino ML, Diéguez JC, Prados D. rHuEpo for the treatment of anemia in myelofibrosis with myeloid metaplasia. Experience in 6 patients and meta-analytical approach. Haematologica. Jul 1998;83(7):616-21. [Medline]. [Full Text].

  54. Rupoli S, Da Lio L, Sisti S, et al. Primary myelofibrosis: a detailed statistical analysis of the clinicopathological variables influencing survival. Ann Hematol. Apr 1994;68(4):205-12. [Medline].

  55. Silverstein MN, Wollaeger EE, Baggenstoss AH. Gastrointestinal and abdominal manifestations of agnogenic myeloid metaplasia. Arch Intern Med. Apr 1973;131(4):532-7. [Medline].

  56. Tefferi A. Myelofibrosis with myeloid metaplasia. N Engl J Med. Apr 27 2000;342(17):1255-65. [Medline].

  57. Tefferi A, Barrett SM, Silverstein MN, Nagorney DM. Outcome of portal-systemic shunt surgery for portal hypertension associated with intrahepatic obstruction in patients with agnogenic myeloid metaplasia. Am J Hematol. Aug 1994;46(4):325-8. [Medline].

  58. Tefferi A, Mesa RA, Gray LA, et al. Phase 2 trial of imatinib mesylate in myelofibrosis with myeloid metaplasia. Blood. May 15 2002;99(10):3854-6. [Medline]. [Full Text].

  59. Tefferi A, Silverstein MN, Li CY. 2-Chlorodeoxyadenosine treatment after splenectomy in patients who have myelofibrosis with myeloid metaplasia. Br J Haematol. Nov 1997;99(2):352-7. [Medline].

  60. Terui T, Niitsu Y, Mahara K, Fujisaki Y, et al. The production of transforming growth factor-beta in acute megakaryoblastic leukemia and its possible implications in myelofibrosis. Blood. Apr 1 1990;75(7):1540-8. [Medline]. [Full Text].

  61. Wang JC, Lang HD, Lichter S, Weinstein M, Benn P. Cytogenetic studies of bone marrow fibroblasts cultured from patients with myelofibrosis and myeloid metaplasia. Br J Haematol. Feb 1992;80(2):184-8. [Medline].

  62. Yanagida M, Ide Y, Imai A, et al. The role of transforming growth factor-beta in PEG-rHuMGDF-induced reversible myelofibrosis in rats. Br J Haematol. Dec 1997;99(4):739-45. [Medline].

  63. Yoon SY, Li CY, Mesa RA, Tefferi A. Bone marrow effects of anagrelide therapy in patients with myelofibrosis with myeloid metaplasia. Br J Haematol. Sep 1999;106(3):682-8. [Medline].

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Further Reading

Related eMedicine Topics

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Keywords

agnogenic myeloid metaplasia with myelofibrosis, AMM, agnogenic myeloid metaplasia, myeloid metaplasia, idiopathic myelofibrosis, aleukemic myelosis, nonleukemic myelosis, myelosclerosis, leukoerythroblastic anemia with diffuse osteosclerosis, megakaryocytic splenomegaly, anemia, bone marrow fibrosis, extramedullary hematopoiesis, leukoerythroblastosis, hepatosplenomegaly, hematopoietic system, chronic myeloid leukemia, CML, chronic myelogenous leukemia, chronic myelocytic leukemia, polycythemia vera, essential thrombocytosis

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Contributor Information and Disclosures

Author

Asheesh Lal, MBBS, MD, Physician, Department of Internal Medicine, Lexington Medical Center
Asheesh Lal, MBBS, MD is a member of the following medical societies: American Society of Clinical Oncology and American Society of Hematology
Disclosure: Nothing to disclose.

Medical Editor

Karen Seiter, MD, Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College
Karen Seiter, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, and American Society of Hematology
Disclosure: Novartis Honoraria Speaking and teaching; Schering Honoraria Speaking and teaching; Cephalon Honoraria Speaking and teaching

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Troy H Guthrie, Jr, MD, Director of Cancer Institute, Baptist Medical Center
Troy H Guthrie, Jr, MD is a member of the following medical societies: American Federation for Medical Research, American Medical Association, American Society of Hematology, Florida Medical Association, Medical Association of Georgia, and Southern Medical Association
Disclosure: Nothing to disclose.

CME Editor

Rajalaxmi McKenna, MD, FACP, Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University
Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, and New York Academy of Sciences
Disclosure: Nothing to disclose.

 
 
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