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Biomedical subjects

F R Appelbaum

Publications and source records attributed to F R Appelbaum.

At least 235 records · Page 13Linked to original sources
PubMed1994

Treatment outcome with chemotherapy in acute promyelocytic leukemia: the Southwest Oncology Group (SWOG) experience.

Because of interest in new approaches to treatment of patients with acute promyelocytic leukemia (APL), we analyzed APL treatment outcome in SWOG with chemotherapy from 1982-1991. To evaluate effects of change in nonspecific patient care factors over time we evaluated outcome in two temporal groups (1982-1986, 1986-1991), corresponding to two groups of treatment protocols encompassing all new de novo AML patients entered on acute myeloblastic leukemia (AML) protocols during those years. Surprisingly, APL patients in the 1982-1986 group (n = 45) had much better treatment outcome (complete remission (CR) rate 71%, median overall survival (OS) 106 months, median disease-free survival (DFS) > 105 months) than the later group (n = 96) (CR rate 47%, median OS 13 months, median DFS 28 months) (p = 0.0063, 0.0015, and 0.0001 respectively). All APL patients but two in the 1982-1986 time period were treated on SWOG protocol 8124, which included induction with total daunorubicin (DNR) 210 mg/m2 i.v./course, consolidation with two courses with identical dosage of DNR, and intensification at 4 months including another course of identical dosage DNR. We analyzed factors affecting treatment outcome for all patients with APL treated from 1982 to 1991. In multivariate analysis, higher DNR induction dose was significantly associated with CR rate, OS, and DFS (p < 0.001, < 0.0001, and < 0.0001, respectively). Cytosine arabinoside (ARA-C) dose and inclusion of other agents did not correlate significantly with outcome. Because these studies were not randomized for DNR dosage, other factors contributing to outcome cannot be completely excluded, although none were found. Most deaths occurred within 3 months of initiation of therapy on 8124; there were no relapses with higher DNR dosage after 3 years. This excellent outcome should be considered in evaluating newer modalities of therapy such as all-trans retinoic acid (ATRA) for APL. If the high CR induction rate and minimal early deaths with ATRA therapy can be combined successfully with this chemotherapy, most patients with APL may be curable.

Antineoplastic Agents↗
PubMed1994

Phase I study of recombinant human interleukin-1 beta (rhIL-1 beta) in patients with bone marrow failure.

The administration of recombinant human interleukin-1 beta (rhIL-1 beta) stimulates pluripotent cell growth and reduces mortality from infection in animal models. In this phase I trial, rhIL-1 beta (0.02-0.50 microgram/kg) was administered by 30-minute intravenous infusion once daily for 2 or 5 consecutive days. The dose was escalated with the subsequent cycle in the same patient if no hematologic response was observed. Nineteen patients with severe bone marrow failure received 60 courses of IL-1 beta. Diagnoses included autologous bone marrow transplant (BMT) (n = 5), allogeneic BMT (n = 7) or idiopathic aplastic anemia (n = 6) and 1 patient with chronic myeloid leukemia. Toxicities included fever (89%), chills (85%), hypertension (89%), hypotension (57%) and headache (95%). No complications were life-threatening and all either spontaneously resolved or were managed pharmacologically. In 8 of 19 patients there was an acute, transient increase in neutrophil counts. In 2 patients there was a transient increase in platelet count; however, no durable, clinically significant effects on peripheral blood counts were observed. In conclusion, administration of rhIL-1 beta in this population of patients had limited efficacy and moderate toxicity.

Adolescent↗
PubMed1994

Phase I study of high-dose busulfan, melphalan and thiotepa with autologous stem cell support in patients with refractory malignancies.

The purpose of this study was to determine the maximal tolerated dose of thiotepa administered with busulfan 12 mg/kg and melphalan 100 mg/m2 followed by autologous stem cell transplantation in patients with refractory malignancies. Twenty-eight patients with refractory malignancies received high-dose busulfan 12 mg/kg, melphalan 100 mg/m2 and escalating doses of thiotepa 450-550 mg/m2 followed by infusion of cryopreserved autologous peripheral blood stem cells (n = 26) or marrow (n = 2). The maximum tolerated dose was determined to be busulfan 12 mg/kg, melphalan 100 mg/m2 and thiotepa 500 mg/m2. Two of three patients receiving thiotepa 550 mg/m2 experienced grade 3 colitis. Twenty patients were enrolled at the maximum tolerated dose and the incidence of grade 3-4 regimen-related toxicity and mortality was 10% and 5%, respectively. Ninety-five per cent of patients experienced grade 1-2 mucositis, 50% grade 1-2 gastrointestinal toxicity, 35% grade I hepatic toxicity and 20% experienced grade 1-2 skin toxicity. The median time to achieve a granulocyte count of 0.5 x 10(9)/I was 10 days (range 8-20 days) and platelet transfusion independence was 10 days (range 1-26 days). Five of ten patients with stage 4 refractory breast cancer achieved a complete and two a partial remission with a complete response rate of 50% and a overall response rate of 70%. In conclusion, busulfan, melphalan and thiotepa can be administered in high doses with tolerable mucositis as the major side-effect. This combination has significant activity in patients with breast cancer, and phase II studies in patients with breast cancer and other chemotherapy sensitive malignancies are warranted.

Adolescent↗
PubMed1994

Comparison of morbidity and mortality after marrow transplantation from HLA-genotypically identical siblings and HLA-phenotypically identical unrelated donors.

The nature and incidence of life-threatening or fatal toxicity after marrow transplantation were analyzed in 52 patients who received HLA-A, B, DR, Dw-phenotypically identical marrow transplants from unrelated volunteer donors (URD). An age and disease-matched cohort of 104 patients transplanted from HLA-genotypically identical siblings was used as a comparative group. The actuarial probability of grade 3 or 4 regimen-related toxicity was 31% after URD transplants and 21% after matched sibling transplants (log-rank p = 0.1041). The median duration of first hospitalization was 33 days for recipients of genotypically-identical marrow and 36 days for recipients of URD marrow (p = 0.0244). Sixty percent of genotypically identical marrow recipients and 51% of unrelated volunteer donor marrow recipients were discharged home from Seattle free of disease at a median of 99 days post-transplant (p = 0.5095). The percentage of patients requiring readmission to hospital and the actuarial probability of requiring either hemodialysis or mechanical ventilation were not statistically different between the two groups. We conclude that matched URD marrow transplantation is not associated with significantly greater regimen-related toxicity or mortality than transplantation from HLA-genotypical siblings.

Adolescent↗
PubMed1994

Recipient-specific donor cytotoxic T lymphocytes enhance engraftment of unrelated, DLA non-identical canine marrow.

Resistance to canine marrow grafts from unrelated DLA non-identical donors can be overcome by infusion of viable donor peripheral blood leukocytes or thoracic duct cells in addition to the marrow. The mechanisms by which these cells enhance engraftment are unknown but are likely to include a graft-versus-host reaction. The current study investigated whether recipient-specific, donor alloreactive cytotoxic lymphocytes mediating a graft-versus-host reaction could abrogate resistance to canine marrow grafts. To this purpose, cytotoxic donor lymphocytes (CTL) specific for recipient DLA antigens were generated in vitro and expanded in culture by exogenous interleukin-2 (IL-2). Two groups of dogs were studied. All were given 9.2 Gy total body irradiation followed by 3.7 x 10(8) marrow cells/kg from an unrelated DLA non-identical donor on day 0 and 1.2 x 10(8) host-specific CTL/kg on days 1 and 2. Dogs in group 2 were given, in addition, subcutaneous injections of recombinant human IL-2, 10,000 U/kg twice daily on days 1 through 10 post-grafting. Ten of 16 dogs in the two groups showed hematopoietic engraftment regardless of whether they received in vivo IL-2. Engraftment in current dogs was significantly better than that in 47 controls given marrow alone (p = 0.001), although it was worse than that in 64 dogs given marrow and an order of magnitude higher number of viable mononuclear cells obtained from the peripheral blood (p = 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Stimulation of hematopoiesis in vivo by stem cell factor.

The ligand for c-kit, known as stem cell factor, mast cell growth factor, or kit ligand, plays a central role in normal hematopoietic stem cell, melanocyte, and gametocyte development and function during embryogenesis and in adult life. In vitro, stem cell factor promotes the survival of hematopoietic progenitors and enhances their proliferation in response to specific growth factors. Administration of recombinant soluble stem cell factor to rodents, dogs, and baboons produces a broad array of effects on hematopoiesis, though not all lineages are equally stimulated. At doses of more than 100 micrograms/kg/d stem cell factor stimulates neutrophilia, lymphocytosis, basophilia, and reticulocytosis and increases mast cells in multiple tissues. In vivo mast cell activation can occur. Marrow cellularity is increased and progenitor cells are increased in marrow, spleen, and blood, and marrow-repopulating cells are increased in the circulation of stem cell factor-treated animals. Stem cell factor synergizes with other hematopoietic growth factors in vivo. Low-dose stem cell factor, 25 micrograms/kg/d, that does not elicit a detectable biological response, enhances the effects of granulocyte colony-stimulating factor in vivo, increasing the neutrophilia and circulation of progenitor and marrow-repopulating cells above that which is achieved with either factor alone. In phase I human trials, dose-limiting toxicities, related to mast cell activation, were reached at 25 to 50 micrograms/kg/d of recombinant human stem cell factor. At these doses, progenitor and long-term culture-initiating cells are increased in marrow and increases in circulating levels of progenitor cells of multiple types are observed. Phase I-II trials of low-dose stem cell factor in combination with granulocyte colony-stimulating factor show that the combination increases the circulation of CD34+ cells and colony-forming progenitor cells. Further studies are needed to determine the therapeutic role of stem cell factor and its effects on expansion and maintenance of hematopoietic stem cells in vivo.

Animals↗
PubMed1994

Hematopoietic effects and clinical uses of granulocyte-macrophage colony-stimulating factor and PIXY321.

The clinical uses of granulocyte-macrophage colony-stimulating factor (GM-CSF) are expanding. GM-CSF was originally approved for use after autologous bone marrow transplantation. More recent phase III studies using GM-CSF after allogenic marrow transplantation show a similar reduction in the duration of neutropenia and monocytopenia. In phase III trials following standard-dose chemotherapy, GM-CSF significantly reduced treatment-related neutropenia and morbidity and, in one study, mortality. Nonrandomized studies using GM-CSF prior to and during chemotherapy for acute myeloid leukemia to improve remission rates have not demonstrated an obviously significant benefit. Other studies of GM-CSF to augment cancer therapies directly and to aid in the treatment of infection are in progress. PIXY321 is a fusion protein of GM-CSF and interleukin-3. PIXY321 was developed, in part, because in vitro and in vivo laboratory studies suggested synergy between its two components. Phase I-II clinical studies using PIXY321 are preliminary but show encouraging results with stimulation of multilineage hematopoiesis.

Animals↗
PubMed1993

The use of colony stimulating factors in marrow transplantation.

Colony stimulating factors (CSF) are now widely used in marrow transplantation. Randomized trials have shown that granulocyte macrophage-CSF accelerates marrow recovery after autologous marrow transplantation, resulting in fewer infections, shorter hospitalization, and lower costs. Similar results have been seen with granulocyte-CSF. Both factors also can accelerate engraftment after allogenic marrow transplantation, but there is, so far, less evidence for clinical benefit in this setting. Both granulocyte macrophage-CSF and granulocyte-CSF benefit some patients with graft failure. The recent demonstration that both granulocyte-CSF and granulocyte macrophage-CSF can mobilize large numbers of hematopoietic stem cells into peripheral blood has resulted in the widespread use of this technique as an alternative to autologous marrow transplantation. A number of colony stimulating factors, including IL-1, IL-3, and steel factor, which act on early hematopoietic progenitors, have recently been entered into clinical trials, with the hope that the progress already made with G-CSF and GM-CSF can be continued.

Bone Marrow Transplantation↗
PubMed1993

Phase I trial with recombinant human interleukin-3 in patients with lymphoma undergoing autologous bone marrow transplantation.

Recombinant human interleukin-3 (rhIL-3) was administered to 30 patients undergoing autologous bone marrow transplant (ABMT) for treatment of lymphoma. In this phase I dose escalation study, rhIL-3 was administered from day 0 to 20 after ABMT by 2-hour intravenous infusion at dose levels of 1, 2, 5, and 10 micrograms/kg/d. Seventeen patients did not complete therapy with rhIL-3. Eleven requested early discontinuation for malaise, confusion, transplant complications, or rapid engraftment and were removed from the study, whereas six patients developed grade III toxicity, including fever (three patients), or headache (three patients) possibly attributable to rhIL3. Other common toxicities included diarrhea, rigors, mucositis, and rash. The maximum tolerated dose of rhIL-3 was 2 micrograms/kg/d. No evidence of earlier hematopoietic cell recovery was observed compared with similar historical patients treated with recombinant human granulocyte-macrophage colony-stimulating factor. Future trials will be needed to determine alternate schedules of administration of rhIL-3 or the use of rhIL-3 in combination or in sequence with other growth factors.

Adult↗
PubMed1993

Radiolabeled-antibody therapy of B-cell lymphoma with autologous bone marrow support.

BACKGROUND: Radiolabeled monoclonal antibodies recognizing B-lymphocyte surface antigens represent a potentially effective new therapy for lymphomas. We assessed the biodistribution, toxicity, and efficacy of anti-CD20 (B1 and 1F5) and anti-CD37 (MB-1) antibodies labeled with iodine-131 in 43 patients with B-cell lymphoma in relapse. METHODS: Sequential biodistribution studies were performed with escalating doses of antibody (0.5, 2.5, and 10 mg per kilogram of body weight) trace-labeled with 5 to 10 mCi of 131I. The doses of radiation absorbed by tumors and normal organs were estimated by serial gamma-camera imaging and tumor biopsies. Patients whose tumors were estimated to receive greater doses of radiation than the liver, lungs, or kidneys (i.e., patients with a favorable biodistribution) were eligible for therapeutic infusion of 131I-labeled antibodies according to a phase 1 dose-escalation protocol. RESULTS: Twenty-four patients had a favorable biodistribution, and 19 received therapeutic infusions of 234 to 777 mCi of 131I-labeled antibodies (58 to 1168 mg) followed by autologous marrow reinfusion, resulting in complete remission in 16, a partial response in 2, and a minor response (25 to 50 percent regression of tumor) in 1. Nine patients have remained in continuous complete remission for 3 to 53 months. Toxic effects included myelosuppression, nausea, infections, and two episodes of cardiopulmonary toxicity, and were moderate in patients treated with doses of 131I-labeled antibodies that delivered less than 27.25 Gy to normal organs. CONCLUSIONS: High-dose radioimmunotherapy with 131I-labeled antibodies is associated with a high response rate in patients with B-cell lymphoma in whom antibody biodistribution is favorable.

Antibodies, Monoclonal↗
PubMed1993

Syngeneic transplantation with peripheral blood mononuclear cells collected after the administration of recombinant human granulocyte colony-stimulating factor.

Five syngeneic transplants were performed in four patients following myeloablative therapy using unmodified peripheral blood mononuclear cells (PBMCs) collected after the administration of recombinant human granulocyte colony stimulating factor (rhG-CSF) to normal donors. The only toxicity experienced by the four normal donors was bone pain. Four patients received two collections of PBMCs, and a second transplant was performed in one patient with one collection. The patients received a median of 20.53 x 10(8) total nucleated cells/kg (range 20 to 25.5), 11.3 x 10(8) total mononuclear cells/kg (range 6.52 to 17.2), 113.1 x 10(4)/kg CFU-GM (range 46.7 to 211.8) and 9.6 x 10(6) CD34+ cells/kg (range 1.6 to 12.6) Post-transplant growth factors were not administered. The median time to an absolute neutrophil count greater than 0.5 x 10(9)/L was 14 days (range 10 to 18). The median time to platelet transfusion independence was 11 days (range 10 to 13). Two patients had the number of CD3+ T lymphocytes determined in the pheresis product. An average of 3.04 x 10(10) CD3+ cells were collected per pheresis. This represents an approximate 1 log increase over the number of T lymphocytes in a typical bone marrow transplant. Rh-GCSF can be used to mobilize peripheral blood progenitor cells from normal donors with minimal toxicity. Studies of allogeneic transplants using PBMCs collected after rhG-CSF administration to determine permanent grafting ability and the incidence and severity of graft-versus-host disease are warranted.

Adult↗
PubMed1993

A randomized controlled trial of pentoxifylline for the prevention of regimen-related toxicities in patients undergoing allogeneic marrow transplantation.

This study evaluated the effect of pentoxifylline (PTX) on the incidence of regimen-related toxicity in patients receiving allogeneic marrow transplants from related donors. All patients received a regimen of methotrexate and cyclosporine as prophylaxis against acute graft-versus-host disease (GVHD). Patients were randomized to receive PTX or a placebo for 70 days and the outcome was examined in a blinded fashion. Forty-four patients were evaluate in each study arm. PTX had no significant effect on engraftment, the incidence of GVHD, venocclusive disease of the liver, infection, the need for oxygen, posttransplant survival, or the duration of hospitalization. Patients receiving PTX were significantly more likely to develop major elevations of serum creatinine levels. PTX was poorly tolerated and induced significantly more vomiting than the placebo. PTX as administered in this randomized study was associated with significant toxicity and offered no benefit in reducing transplant-related morbidity or mortality.

Adolescent↗
PubMed1993

Long-term follow-up of patients with invasive fungal disease who received adjunctive therapy with recombinant human macrophage colony-stimulating factor.

Mortality of bone marrow transplant (BMT) patients who develop invasive fungal infection is greater than 80%. Long-term follow-up of 46 consecutive BMT patients who received recombinant human macrophage colony-stimulating factor (rhM-CSF) as adjunctive therapy with standard antifungal treatment who were entered into phase I/II trials at The Fred Hutchinson Cancer Research Center is reported. rhM-CSF (100 micrograms/m2 to 2,000 micrograms/m2; Chiron/Cetus Corporation, Emeryville, CA) was administered from day 0 to 28 after determination of progressive fungal disease. Results of long-term follow-up of fungal infection, relapse, and survival were compared with 58 similar historical controls. Multivariable analysis of the patients who received rhM-CSF showed two factors that significantly correlated with poor survival: Karnofsky score < or = 20% and Aspergillus infection. Overall, survival of patients who received rhM-CSF was greater than that of historical patients (27% v 5%) and was entirely because of a 50% survival rate in patients with Candida infection and Karnofsky scores greater than 20%. Prospective, randomized, controlled trials to determine efficiency of rhM-CSF are indicated and should be directed at patients with invasive candidiasis.

Adult↗
PubMed1993

Allogeneic bone marrow transplantation for 93 patients with myelodysplastic syndrome.

We treated 93 patients with myelodysplastic syndrome using cyclophosphamide and either total body irradiation (n = 88) or busulfan (n = 5) followed by marrow transplantation. Sixty-five marrow donors were genotypically HLA-identical siblings and 28 were other family members or unrelated donors. Before transplantation all patients had either severe neutropenia or thrombocytopenia or had greater than 5% blasts in the marrow or peripheral blood. The probabilities of disease-free survival, relapse, and non-relapse mortality at 4 years were 41%, 28%, and 43%, respectively. Multivariate analysis revealed that younger age and shorter disease duration were significantly associated with improved disease-free survival and decreased non-relapse mortality. Relapse was seen only in patients with excess blasts at the time of transplantation (51% at 4 years). Patients younger than age 40 and without excess blasts had a 4-year disease-free survival of 62%. This study confirms that allogeneic marrow transplantation can cure some patients with myelodysplasia. Because of the favorable outcome in younger patients without excess blasts, we recommend that transplantation be considered early for patients younger than age 40, before disease progression or development of life-threatening cytopenias. For older patients and those with excess blasts, changes in the transplant procedure will be necessary to improve outcome.

Adolescent↗
PubMed1993

Marrow toxicity of fractionated vs. single dose total body irradiation is identical in a canine model.

PURPOSE: We explored in dogs the marrow toxicity of single dose total body irradiation delivered from two opposing 60Co sources at a rate of 10 cGy/min and compared results to those seen with total body irradiation administered in 100 cGy fractions with minimum interfraction intervals of 6 hr. Dogs were not given marrow transplants. RESULTS: We found that 200 cGy single dose total body irradiation was sublethal, with 12 of 13 dogs showing hematopoietic recovery and survival. Seven of 21 dogs given 300 cGy single dose total body irradiation survived compared to 6 of 10 dogs given 300 cGy fractionated total body irradiation (p = .18). One of 28 dogs given 400 cGy single dose total body irradiation survived compared to none of six given fractionated radiation (p > .20). With granulocyte colony stimulating factor administered from day 0-21 after 400 cGy total body irradiation, most dogs survived with hematological recovery. Because of the almost uniform success with granulocyte colony stimulating factor after 400 cGy single dose total body irradiation, a study of granulocyte colony stimulating factor after 400 cGy fractionated total body irradiation was deemed not to be informative and, thus, not carried out. Additional comparisons between single dose and fractionated total body irradiation were carried out with granulocyte colony stimulating factor administered after 500 and 600 cGy of total body irradiation. As with lower doses of total body irradiation, no significant survival differences were seen between the two modes of total body irradiation, and only 3 of 26 dogs studied survived with complete hematological recovery. Overall, therefore, survival among dogs given single dose total body irradiation was not different from that of dogs given fractionated total body irradiation (p = .67). Similarly, the slopes of the postirradiation declines of granulocyte and platelet counts and the rates of their recovery in surviving dogs given equal total doses of single versus fractionated total body irradiation were indistinguishable. CONCLUSION: Within the limitations of the experimental design, we conclude that single-dose and fractionated total body irradiation have comparable marrow toxicity in dogs.

Animals↗
PubMed1993

A prospective randomized comparison of total body irradiation-etoposide versus busulfan-cyclophosphamide as preparatory regimens for bone marrow transplantation in patients with leukemia who were not in first remission: a Southwest Oncology Group study.

Two novel preparatory regimens for conditioning of patients with leukemia for allogeneic bone marrow transplantation (BMT) from histocompatible sibling donors have been tested in a phase III trial under the auspices of the Southwest Oncology Group (SWOG 8612). These two regimens consisted either of fractionated total body irradiation and etoposide (FTBI/VP-16) or high-dose busulfan with cyclophosphamide (BU/CY). Only patients who had failed prior conventional management at least once were study eligible, ie, no patients with acute leukemia in first remission (CR) or in first chronic phase (CP) of chronic myelogenous leukemia (CML) participated. Patients were stratified according to the following risk criteria: "good-risk" patients were those who were in second CR of their acute leukemia or in accelerated phase (AP) of CML; "poor-risk" patients had further advanced stages of leukemia. During a 52-month period, 131 patients were registered of whom 122 (93%) were study eligible. Sixty-one eligible patients were randomized to the FTBI/VP-16 arm and 61 to the BU/CY regimen. Of these 122 patients, 114 (93%) proceeded to BMT according to protocol. Posttransplant immunosuppression to prevent graft-versus-host disease (GVHD) consisted of cyclosporine and prednisone (CSA/PSE). Neither overall survival nor disease-free survival (DFS) differed significantly between the two treatment groups (P = .89 and .69, respectively). Estimated DFS for "good-risk" patients who had been prepared with the FTBI/VP-16 regimen was 55% +/- 11%, as compared with patients treated with BU/CY whose DFS figure was 34% +/- 10% (P = .30). For "poor-risk" candidates, the DFS rates at 24 months were 17% +/- 6% (for FTBI/VP-16) and 24% +/- 8% (for BU/CY), respectively (P = .81). These figures do not differ significantly, especially in view of the fact that the "good-risk" patients prepared with the FTBI/VP-16 regimen were younger than those treated with BU/CY. Both regimens were well tolerated with no regimen-related deaths encountered during the 6-week period after BMT. This study also confirmed the efficacy of the CSA/PSE combination in the prevention of GVHD with 23 of 113 (20%) of BMT recipients developing moderate to severe acute GVHD. The leading cause for treatment failure was leukemic relapse (45 of the 114 BMT recipients suffered a recurrence of their leukemia), whereas 38 patients died without evidence of relapse. Thirty-one patients are alive and in continued CR after marrow transplantation; four are alive in relapse.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1993

The effects of daily recombinant human granulocyte colony-stimulating factor administration on normal granulocyte donors undergoing leukapheresis.

The effects of daily administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to eight normal volunteers donating granulocytes for neutropenic relatives undergoing marrow transplantation were studied. Granulocyte donors consisted of seven marrow donors (5 syngeneic, 2 HLA identical) and one haploidentical son who had not donated marrow. All donors were administered daily rhG-CSF at a mean dose of 5 micrograms/kg/d (range 3.5 to 6.0) for a mean of 11.75 days (range 9 to 14 days), and granulocytes were collected a mean of 7.6 times (range 4 to 12). RhG-CSF was well tolerated and only minor side effects were observed. All donors became anemic from marrow donation and the removal of red blood cells during the collection procedures. Red blood cell transfusions were not given. All donors had a decrease in platelet counts and the magnitude of the decrement appeared to be greater than in historical donors. This was due in part to increased removal of platelets with the collection product, but a direct effect of rhG-CSF on platelet production cannot be excluded. The mean precollection granulocyte level was 29.6 x 10(9)/L (range 11.8 to 79.8), which was a 10-fold increase over baseline. The mean number of granulocytes collected was 41.6 x 10(9) (range 1.3 to 144.1), which was a six-fold increase over historical donors not receiving rhG-CSF. The mean granulocyte level 24 hours after transfusion into neutropenic recipients was 0.95 x 10(9)/L (median 0.57 and range .06 to 9.47). This study indicates that rhG-CSF is safe to administer to normal individuals, significantly improves the quantity of granulocytes collected, and results in significant circulating levels of granulocytes in neutropenic recipients. Further studies to evaluate rhG-CSF in normal granulocyte donors are warranted.

Adult↗