Effect of Granulocyte Colony-Stimulating Factor after Intensive Induction Therapy in Relapsed or Refractory Acute Leukemia

Abstract

Background. Although colony-stimulating factors have been shown to accelerate recovery from severe neutropenia after intensive chemotherapy or bone marrow transplantation, their use in acute leukemia has been controversial because in vitro they stimulate leukemic colonies as well as normal granulocyte colonies. Methods. We conducted a prospective, randomized, controlled study to determine the safety and efficacy of recombinant human granulocyte colony-stimulating factor (CSF) after a standard course of intensive therapy in 108 patients with relapsed or refractory acute leukemia (67 with acute myelogenous leukemia, 30 with acute lymphocytic leukemia, 9 in blast crisis from chronic myelogenous leukemia, and 2 with acute leukemia arising from myelodysplastic syndromes). Treatment with granulocyte CSF (200 micrograms per square meter of body-surface area per day in a 30-minute infusion) was begun two days after the end of the chemotherapy and continued until the neutrophil count rose above 1500 per cubic millimeter. Results. Treatment with granulocyte CSF accelerated the recovery of neutrophils significantly (P less than 0.01), shortening it by about a week, but it had no effect on platelet recovery. Although the incidence of febrile episodes was almost the same, documented infections were significantly less frequent in the group treated with granulocyte CSF (P = 0.028). There was no evidence that granulocyte CSF accelerated the regrowth of leukemic cells. Fifty percent of 48 patients in the CSF group who could be evaluated and 36 percent of 50 controls had complete remission. The rate of relapse was almost the same in the two groups. Conclusions. It appears that recombinant human granulocyte CSF is safe in acute leukemia, accelerating neutrophil recovery and thereby reducing the incidence of documented infection without affecting the regrowth of leukemic cells. It should be used with caution, however, pending further confirmation of these early results.

Leukemic cells with 11q23 translocations express granulocyte colony-stimulating factor (G-CSF) receptor and their proliferation is stimulated with G-CSF

“…The results were shown as the stimulation index at each of the G-CSF concentrations. multicentric analysis will be required because G-CSF may improve event-free survival by preventing severe infections and/or shortening the interval between programs of chemotherapy, 40,41 as reported in AML by Ohno et al 12 On the contrary, it is highly possible that use of G-CSF during chemotherapy enhances the cytotoxic effects of anti-leukemic agents by inducing leukemic cells with 11q23 translocations from G 0 -phase into the chemotherapy-sensitive G 1 -and S-phases as reported in GM-CSF. 42 In this regard, it may be very useful to use G-CSF, together with a preconditioning regimen, in autologous or allogeneic bone marrow transplantation for leukemia with 11q23 translocations.…”

“…3,[7][8][9][10][11] Accordingly, in patients with these leukemias, granulocyte colony-stimulating factor (G-CSF) is commonly used for severe neutropenia following multidisciplinary chemotherapy and/or transplantation to help recovery of granulopoiesis. 12,13 Although G-CSF has been initially considered as a factor that acts specifically on cells committed to the neutrophilic granulocyte lineage, 13 it is now known that G-CSF supports the survival, proliferation, and differentiation of multipotential hematopoietic stem cells [14][15][16][17][18][19] as well as granulocytic precursors. In addition, we recently showed that normal B-precursor cells increased in bone marrow after chemotherapy, express G-CSF receptor (G-CSFR), suggesting a possible participation of the G-CSF/G-CSFR interaction in the process of B cell ontogeny.…”

Effects of interleukin-3 on myelosuppression induced by chemotherapy for ovarian cancer and small cell undifferentiated tumours

“…Use of haematopoietic growth factors may prove beneficial by reducing toxicity of chemotherapy. Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage CSF (GM-CSF) have clearly reduced the depth and extent of neutrophil nadirs, and reduced the incidence of serious infection (Ohno et al, 1990;Crawford et al, 1991;de Vries et al, 1991). Unfortunately, neither G-CSF nor GM-CSF could adequately ameliorate thrombocytopenia due to cytotoxic therapy and therefore may not permit significant dose escalation of drugs which are associated with thrombocytopenia.…”

Changes in the Incidence and Etiological Patterns of Bacteremia Associated with Acute Leukemia over a 25-Year Period.

“…1). The rhG-CSF was administered mainly to patients with ALLas well as those with relapsed or refractory acute leukemia (7). All but transplant patients were treated on one 40-bed hospital floor and exposed to similar potential environmental contaminants under routine hospital care.…”