14.          Non-Leukemic Chronic Myeloproliferative Disorders

14.1        General considerations

The non-leukemic chronic myeloproliferative disorders (CMPD) are a group of pre-leukemic disorders characterized by proliferation of one or more lineages of the myelo-erythroid series. The WHO classification of the CMPD recognizes seven entities, including four non-leukemic ones.

• From Vardiman et al

Literature: for review e.g.

      BENCH et al, Best Pract. Res. Clin. Haematol. 14 (2001): 531-551

      CERVANTES, Pathol. Biol. 49 (2001): 148 – 152

• VADIRMAN et al, Blood 100 (2002): 2292 – 2302 (WHO classification of the  myeloid neoplasms)

14.2        Chronic idiopathic myelofibrosis (myelofibrosis with metaplasia, MMM)

General considerations

Myelofibrosis with myeloid metaplasia (MMM) is the designation of a myeloproliferative disorder in which fibrosis of normal bone marrow compartment (occurring in response to an abnormal stem cell clone of megakaryocytic or monocytic origin) is accompanied by extramedullary hematopoiesis in the enlarged spleen, liver and other atypical sites. Massive splenomegaly can also lead to a significant sequestration of erythrocytes and platelets, which exacerbates the underlying cytopenias caused by marrow hypofunction.

Current conventional therapy of MMM has its focus on palliation but has no impact on survival. It includes red blood cell transfusions and treatment of anemia with androgens (nandrolone, oxymetholne, fluoxymesterolone, methandrostenolone, testosterone ethenate). Corticosteroids or erythropoietin. Peripheral signs of hyperproliferation can be treated with hydroxyurea (recommended initial dose 30 mg/kg twice weekly, maintainance dose 500 mg/d ) or interferon alpha (e.g. 5 x 10⁶ IU s.c. 3-5 times weekly, especially for patients < 45 years).

Splenectomy is another palliative procedure in selected patients with progressive transfusion-dependent anemia, painful splenomegaly or hypercatabolic symptoms associated with cytopenia.

Achieving a complete histohematological remission as a prerequisite for a cure is only possible with an allogeneic stem cell transplantation. More recently, preliminary results support the feasibility of reduced- intensity fludarabine- based conditioning prior to allogeneic transplant for older patients.

            Literature: for review e.g.

                        BAROSI, J. Clin. Oncol. 17 (1999): 2954 – 2970 (review)

                        CERVANTES, Pathol. Biol. 49 (2001): 148 – 152  (review)

CERVANTES et al, Br. J. Haematol. 102 (1998): 684 – 690 (allogeneic stem cell transplantation )

DEVINE et al, Blood 99 (2002): 2255-2258 (reduced-intensity conditioning prior to allogeneic stem cell transplantation)

                        GUARDIOLA et al, Blood 93 (1999): 2831 – 2838 (allogeneic stem cell transplantation)

HESSLING et al. Br. J. Haematol. 119 (2002): 769- 772 (reduced- intensity conditioning prior to allogeneic stem cell transplantation)

                        MESA and TEFFERI, Leuk, Lymphoma 42 (2001): 901 – 911 (splenectomy)

                        L1 and DEEG, Leukemia 15 (2001): 465 – 467 (splenectomy)