JUVENILE CHRONIC MYELOGENOUS LEUKEMIA - IN-VITRO CHARACTERIZATION BEFORE AND AFTER ALLOGENEIC BONE-MARROW TRANSPLANTATION

In previously published studies on patients with juvenile chronic myel ogenous leukemia (JCML), excessive proliferation of malignant monocyte -macrophage elements and impaired growth of normal hematopoietic proge nitors were demonstrated. A selective hypersentivity of granulocyte-ma chrophage progenitors (CFU-GM) to granulocyte-macrophage colon stimula ting factor (GM-CSF) seems to represent the main pathogenetic mechanis m. Allogeneic bone marrow transplantation (BMT) has been demonstrated to be the only curative strategy for patients with JCML. In this study , we evaluated the growth of peripheral blood hematopoietic progenitor s in semisolid cultures in two children with JCML before and after all ogeneic BMT. Serum levels of GM-CSF, interleukin-1 (IL-1) and tumor ne crosis factor-alpha (TNF-alpha) were also assessed. IL-1-beta, GM-CSF and TNF-alpha serum levels of the patients before and after BMT did no t differ significantly from those obtained in 45 healthy controls. Aft er marrow transplant, the engraftment of donor hematopoietic stem cell was associated with the disappearance of both pretransplant GM-CSF hy persensitivity and CFU-GM spontaneous growth. The inhibitory effect on the growth of normal hematopoietic progenitors also resolved. This co nfirms that the substitution of the pathological hematopoietic progeni tors represents the basis for the curvative effect of allogeneic BMT i n the treatment of JCML, abolishing both the excessive responsiveness of JCML progenitor cells even to very low concentrations of GM-CSF and the growth-inhibitory effect on normal hematopoiesis. (C) 1995 Wiley- Liss, Inc.