LeukemiaResearchVol.16.No.1, pp. 95-100.1992.

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T H E R A P E U T I C ASPECTS OF MYELODYSPLASTIC SYNDROMES IN C H R O N I C P H A S E ROBERT HASTt AND EVA HELLSTROM:~ Divisions of Hematology, Departments of Medicine, tDanderyd Hospital and ~Huddinge Hospital, Karolinska Institute, Stockholm, Sweden Abstract--Myelodysplastic syndromes (MDS) include hemopoietic cytopenias of different origin, which are usually refractory to treatment. Therefore MDS patients should generally be treated conservatively. Transfusions of packed red cells (given in a strict regimen to minimize the risk for secondary hemochromatosis) may be sufficient to maintain a good quality of life. Indications for cytotoxic treatment include signs of progression of the disease. In patients with symptomatic cytopenias low-dose cytarabine (ara-C) should be tried. It is essential then to monitor each patient individually and to avoid fixed treatment schedules. Standard (high-dose) chemotherapy in MDS, is associated with a high mortality and a low response rate, and should be considered only in younger patients with advanced MDS. Allogeneic bone marrow transplantation (BMT) may be offered to younger MDS patients, when a suitable donor is available. Treatment with differentiation inducers has not met with expectations and should not be used outside clinical trials at the present. The use of recombinant hemopoietic growth factors (GF) seems promising. GF, like GM-CSF, G-CSF, IL-3, and erythropoietin, can be used either alone or in combinations, to support failing peripheral blood values, and decrease the risk for lethal complications. GF can also be given together with chemotherapy, in an effort to make the leukemic clonogenic cells more susceptible to cytotoxic drugs. Other treatments for MDS include: IFN-et and etoposide, with responses primarily in chronic myelomonocytic leukemia; hem arginate, whose role is still not clear; and corticosteroids, but only in carefully selected cases. Key words: Myeiodysplasia, MDS, treatment, cytotoxic drugs, differentiation induction, growth

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INTRODUCTION

i.e. below 50 years, seem to have a more malignant course than the elderly [1]. Twenty to 30% of all MDS patients develop acute leukemia while about 10% of the patients run a stable and asymptomatic course for many years. MDS patients can be divided into five subgroups according to a suggestion by the FAB-group [1]. The subgroups, MDS 1-5, are defined by the degree of bone marrow dysmaturation at diagnosis. The FAB classification will only give a rough estimate of the prognosis in MDS. The assessment of prognosis in individual cases is helped by the identification of abnormal localization of immature precursors (ALIP) in the bone marrow [3], cytogenetic studies [4], or the use of scoring systems like the Bournemouth score [5] or the Dutcher score [6], both of which also take the peripheral blood values into account. During the 1970s and 1980s we learned a great deal about the nature of MDS, but nevertheless we cannot say which is the best way to treat our patients. Attempts have been made using immunotherapy,

MYELODYSPLASTIC syndromes (MDS) belong to a group of hematopoietic stem cell disorders of clonal origin. MDS is characterized by maturation disturbances in the bone marrow, which result in qualitative and quantitative abnormalities of the peripheral blood cells. The majority of MDS patients are elderly. The etiology is not known, but secondary cases have been described after exposure to mutagenic treatment, especially among younger patients. At diagnosis most patients are in a chronic phase with anemia, often in combination with varying degrees of granulocytopenia and thrombocytopenia. The clinical course of most MDS patients is progressive with increasing degree of bone marrow dysplasia and peripheral blood cytopenia. Younger MDS patients, *Supported by The Karolinska Institute, and Trygg Hansa AB. Correspondence to: Dr Robert Hast, Division of Hematology, Department of Medicine, Danderyd Hospital, S-182 88 Danderyd, Sweden. 95

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hormones, various cytoreductive regimens, differentiation induction agents, bone marrow transplantation, and most recently growth factors. Surprisingly few controlled therapeutic studies have been performed, where active treatment was compared to the outcome of supportive care only. Therefore, current experiences of clinical management of MDS is based mainly on uncontrolled studies. SUPPORTIVE T R E A T M E N T MDS patients should generally be treated conservatively. During the stable chronic phase, packed red cell transfusions may be given, but in a strict regimen to minimize the risk for secondary hemochromatosis. Most patients readily tolerate hemoglobin levels around 80-90 g/l. Patients with recurrent infections may benefit from long-term antibiotic treatment. Transfusions of platelets are rarely needed at this stage. Careful observation of the progression of the disease is the mainstay of the clinical management of MDS. The appearance of septic infections or major bleedings could indicate a progression of the MDS to a more acute stage, where aggressive treatment has to be considered. There are no indications that an earlier start of anti-leukemic therapy would improve the prognosis of the disease. CHEMOTHERAPY Standard (high-dose) chemotherapy is associated with considerable side-effects and a high mortality in the majority of MDS patients. However, successful cases

Therapeutic aspects of myelodysplastic syndromes in chronic phase.

Myelodysplastic syndromes (MDS) include hemopoietic cytopenias of different origin, which are usually refractory to treatment. Therefore MDS patients ...
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