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Sir, - It would certainly be nice if what Amotz Asa-El prescribed were to be done (\"Time to fight Egypt's cold war,\" November 22). Hosni Mubarak's hypocrisy and the danger to Israel of an increasingly heavily armed Egypt under his rule, as well as the influence of Egypt's \"elites,\" cannot be underestimated. Sir, - Aside from the religious consideration of desecrating Shabbat - a very serious matter - secularists should realize that once you start opening businesses on Shabbat you create a situation that completely changes the Jewish complexion of the State of Israel (\"Shabbat opening of Kfar Saba mall sparks religious-secular struggle,\" November 24). Sir, - In response to Nissim Yosha (Letters, November 20) and \"Court orders Yad Vashem to open Righteous Among the Nations files\" (November 13), the title of Righteous is awarded to persons who either risked their lives or their positions in assisting Jews, preventing their deportation, and/or speaking out against the persecution of Jews.

The myelodysplastic syndromes are characterized by ineffective hematopoiesis and refractory cytopenias. In an attempt to improve hematopoiesis, we administered recombinant human granulocyte–macrophage colony-stimulating factor (GM-CSF) to eight patients with myelodysplastic syndrome, as part of a Phase I trial. The GM-CSF was given by continuous intravenous infusion daily for two weeks and then again after a two-week rest period. Over the entire dose range tested (30 to 500 μg per square meter of body-surface area), treatment was associated with marked increases in peripheral-blood leukocytes (5- to 70-fold), including granulocytes (5- to 373-fold), in all eight patients. The absolute number of monocytes, eosinophils, and lymphocytes increased in all patients. Three of eight patients also had 2- to 10-fold increases in platelet counts and improvement in erythropoiesis, with the result that two of three patients who had required red-cell and platelet transfusions no longer needed them (at 20 to 27 weeks of follow-up). Treatment was also associated with increased marrow cellularity and a decreased percentage of blasts in the bone marrow of patients with excess blasts, resulting in an increase in the ratio of differentiated myeloid cells to immature myeloid cells. We observed relatively few side effects, but bone pain was dose-limiting when it was associated with high white-cell counts. Our results showed that GM-CSF is a potent stimulator of hematopoiesis in vivo and may produce hematologic improvement in the short term (8 to 32 weeks of observation) in patients with myelodysplastic syndrome. More experience, with longer follow-up periods, will be necessary to assess the long-term safety and efficacy of this new treatment. (N Engl J Med 1987; 317:1545–52.) THE myelodysplastic syndromes are a group of stem-cell disorders characterized by maturation defects resulting in ineffective hematopoiesis, refractory cytopenias often leading to infection or hemorrhage, and an increased risk of leukemic transformation. 1 2 3 4 5 6 7 No currently available treatment has been shown to be consistently effective in producing sustained improvement in hematopoiesis or in delaying leukemic evolution. 8 9 10 11 Several agents, including retinoids, vitamin D analogues, and cytotoxic drugs such as low-dose cytarabine have been used to treat patients with myelodysplastic syndrome 9 10 11 12 13 14 15 16 17 18 ; this therapy has been based mainly on the agents' potential for inducing differentiation of established leukemic cell lines in vitro. 19 20 21 22 23 The results . . .

Aplastic anemia is a syndrome in which pancytopenia occurs in the presence of hypocellularity of the bone marrow. To assess the biologic activities of recombinant human granulocytemacrophage colony-stimulating factor (GM-CSF) in aplastic anemia, we gave GM-CSF (60 to 500 μg per square meter of body-surface area) to 10 patients with moderate or severe disease, by continuous intravenous infusion daily for two weeks, and repeated the treatment after a two-week rest period. The treatment increased the white-cell count (1.6- to 10-fold) in all patients, primarily because of an increase in the numbers of neutrophils (1.5- to 20-fold), eosinophils (12- to >70-fold), and monocytes (2- to 32-fold). Rates of hydrogen peroxide production in purified granulocyte fractions increased during GM-CSF treatment. Increases in bone marrow cellularity, myeloid precursor cells, and myeloid:erythroid cell ratios accompanied the white-cell response. Despite the in vivo response of the white cells, the concentration of colony-forming cells remained the same. Measurable concentrations of interleukin-2 (2 to 15 units per milliliter) were found in the serum of 8 patients, and high levels of erythropoietin (81 to 1200 IU per liter) were found in 10 patients. The predominant side effects were constitutional symptoms. These results indicate that recombinant human GM-CSF is effective in stimulating myelopoiesis in patients with severe aplastic anemia and may benefit some patients in whom the disorder is refractory to standard forms of therapy. (N Engl J Med 1988; 319:1628–34.) APLASTIC anemia is a hematopoietic disorder characterized by bone marrow failure and pancytopenia. Several mechanisms have been implicated in the pathogenesis of this disease, including the loss of pluripotent stem cells, dysfunction of progenitor cells, defects in the microenvironment of the bone marrow, abnormalities of humoral regulators of hematopoiesis, and autoimmune inhibition of hematopoiesis. 1 2 3 4 5 Transplantation of bone marrow from a histocompatible donor is currently the treatment of choice for patients under the age of 40. 6 7 8 This choice is not available, however, to a majority of patients with severe aplastic anemia, because they either are older or lack a histocompatible donor. . . .