Biomedical subjects

R K Shadduck

Publications and source records attributed to R K Shadduck.

At least 37 records · Page 2Linked to original sources

PubMed1996

Pilot study of combined cryosupernatant and protein A immunoadsorption exchange in the treatment of grade 3-4 bone marrow transplant-associated thrombotic microangiopathy.

Bone marrow transplant-associated thrombotic microangiopathy (BMT-TM) ranges in severity from a self-limiting to a fatal disorder. There is no specific therapy for this condition to date. We have previously described a simple clinical grading system (grade 0-4) for BMT-TM; patients with grade 3-4 BMT-TM do poorly. A previous study in our institution suggested that a combination of exchange with cryosupernatant replacement and protein-A immunoadsorption (PAI) might be of benefit. Therefore we performed a pilot study to evaluate the effectiveness of cryosupernatant alternating with PAI exchange for 2 weeks in a series of 13 patients with grade 3-4 BMT-TM. Twelve of 13 patients had undergone allogeneic-BMT a median of 25 days (range of 5-458 days) prior to the onset of grade 3-4 BMT-TM. The thirteenth patient had undergone autologous peripheral stem cell transplant 11 days prior to grade 4 BMT-TM. Pre-therapy, 10 patients had grade 4 BMT-TM and three had grade 3. Eight (62%) showed a response to treatment. Post-therapy, four responders had grade 3, three had grade 2 and one had grade 0 BMT-TM. The median follow-up of the responders is 90 days (range 21 to 464). Three responders have died at 21, 44, and 226 days following the development of BMT-TM of interstitial pneumonia in one, aspergillus in one, and multiorgan failure syndrome (MOFS) in one. The remaining responders are alive 66-465 days post-TM. All non-responders died of MOFS at 6-31 days post-TM. These results suggest that combined exchange with cryosupernatant alternating with PAI is effective therapy for some patients with moderate to severe BMT-TM and may improve survival.

Adult↗

PubMed1995

Ex vivo purging of allogeneic marrow with L-Leucyl-L-leucine methyl ester. A phase I study.

L-Leucyl-L-leucine methyl ester (LLME) is a lysosomatropic compound that is converted by dipeptidyl peptidase I to metabolites that are membranolytic for cytotoxic T cells, NK cells, and LAK cells. Ex vivo treatment of murine marrow with LLME ameliorates acute graft-versus-host-disease (GVHD), which led to consideration of a clinical study. A phase I study design was initiated to evaluate the effects of ex vivo purging of allogeneic marrow on engraftment, since LLME also suppresses human progenitor cells. All patients received a preparative regimen of cyclophosphamide plus total body irradiation. GVHD prophylaxis consisted of cyclosporine +/- corticosteroids. This study included 19 patients with high risk disease undergoing allogeneic transplantation from an HLA-identical sibling (n = 12) or a partially HLA-matched family donor (n = 7). Marrow mononuclear cells were treated ex vivo in a dosage escalation study with LLME concentrations of 0.25 mM, 0.375 mM, and 0.5 mM. Marrow NK and LAK activities were essentially eliminated at concentrations > or = 0.375 mM LLME. CD8+ cells were also reduced. Granulocyte macrophage colony-forming unit recovery was 3% at 0.5 mM LLME. The median time to an absolute neutrophil count of 500/microliters was 17 days after transplantation (95% confidence interval = 14-18 days). One patient that received marrow treated with 0.5 mM LLME died of secondary graft failure. Complete donor chimerism was documented in each evaluable case. NK recovery was delayed at LLME concentrations > or = 0.375 mM LLME. Grade II/IV GVHD occurred in 4/18 evaluable patients. Ex vivo treatment of human marrow with LLME diminishes NK activity, LAK activity, CD8+ cells, and granulocyte macrophage colony-forming units, but does not totally prevent acute GVHD.

Acute Disease↗

PubMed1995

Identification of a growth factor for primary murine stroma as macrophage colony-stimulating factor.

Knowledge of the stromal microenvironment is crucial for understanding the hematopoietic system. We took advantage of an assay that permits analysis of primary stroma-initiating cells (SICs) on the clonal level, and further characterized SICs and the factors that regulate SICs. Stroma formation in this assay is dependent on a high-molecular-weight factor secreted by the stromal cell line AC3.U. Here we show that this factor is identical to macrophage colony-stimulating factor (M-CSF), and that purified M-CSF is sufficient for induction of stroma formation. M-CSF, isolated from the line AC3.U, as well as from L929 cells and COS cells transfected with an expression vector encoding M-CSF, migrated in two peaks as 160- and 650-kD species after gel filtration. These molecular-weight species encompassed all stroma-inducing activity, and both stimulated macrophage colony formation. Affinity chromatography and blocking studies with antibodies specific for M-CSF and c-fms confirmed M-CSF as the sole factor in the supernatant of the stromal cell line AC3.U that promotes stroma formation. Culture of marrow, for as little as 1 week, depleted M-CSF-dependent SIC while increasing the incidence of replatable, factor-independent SIC. This suggests that culture changes the properties of SICs, perhaps by inducing differentiation into mature stromal cells. Thus, our results show a novel function of M-CSF as an important modulator of stroma formation.

Animals↗

PubMed1995

Colony-stimulating factor-1 secreted by fibroblasts promotes the growth of dendritic cell lines (XS series) derived from murine epidermis.

We have established recently from mouse epidermis long-term dendritic cell lines (XS series) that resemble epidermal Langerhans cells (LC) by their surface phenotype, Ag-presenting profile and cytokine mRNA profile. The growth of XS lines was promoted maximally by granulocyte-macrophage-CSF or by a factor secreted by NS lines, which are fibroblastic cell lines established from dispase-separated specimens of mouse epidermis. The purpose of this study was to determine the identity of XS cell growth factor secreted by NS cells. We report the following: 1) NS cells express constitutively mRNA for CSF-1; 2) XS cells express the CSF-1R at mRNA and protein levels; 3) rCSF-1 mimics NS culture supernatant in its ability to promote XS cell growth; 4) NS supernatant-dependent XS cell growth is blocked completely by each of two Abs against the CSF-1R. We conclude that CSF-1 is responsible for the XS growth-promoting activity secreted by NS lines. We also report the following: 5) LC freshly isolated from skin express CSF-1R mRNA; and 6) fibroblasts derived from specimens of dermis also express mRNA and secrete large amounts (50-100 ng/ml) of CSF-1. These observations give rise to a new concept that dermal fibroblasts may support the survival and growth of LC (and their precursors) through the paracrine effect of elaborated CSF-1.

Animals↗

PubMed1995

Inhibition of day-12 spleen colony-forming units by a monoclonal antibody to the murine macrophage/monocyte colony-stimulating factor receptor.

Primitive hematopoietic stem cells differentiate into committed progenitors that are thought to selectively express hematopoietic growth factor receptor(s), thereby acquiring hematopoietic growth factor responsiveness. To assess whether hematopoietic stem cells express hematopoietic growth factor receptors, the progenitor activity of bone marrow (BM) fractions, isolated by expression of receptors for macrophage/monocyte colony-stimulating factor (M-CSF), were examined. Recovery of day-12 spleen colony-forming units (CFU-S) is diminished in both M-CSF receptor-positive (M-CSFR+) and M-CSFR- fractions, indicating antibody inhibition of day-12 CFU-S. Incubation of BM cells with antibody without fractionation inhibits 50% to 60% of day-12 CFU-S. This inhibition is specific (control antibodies have no effect) and reversible by removal of bound antibody at low pH. Incubating BM cells with control or antireceptor antibody does not affect day-8 CFU-S, which are predominantly erythroid. Treating sublethally irradiated mice with antibody inhibits endogenous day-12 CFU-S. These results indicate that some early progenitors express M-CSFRs, and blocking M-CSFRs inhibits the ability of these progenitors to form colonies, possibly because of inactivation caused by prolonged receptor blockade.

Animals↗

PubMed1995

High-dose cyclosporine and corticosteroids for prophylaxis of acute and chronic graft-versus-host disease.

Twenty-eight consecutive recipients of HLA-identical sibling marrow grafts received prophylaxis for GVHD with high-dose cyclosporine (CsA) and corticosteroids. CsA 5 mg/kg/day (2.5 mg/kg infused over 4 h twice daily) was started on day -1 and continued until patients could take oral CsA (15 mg/kg/day). CsA doses were adjusted to maintain concentrations between 200-800 ng/ml (whole-blood HPLC) until the tapering period (days 268-361). Methylprednisolone 0.5 mg/kg/day was started on day 7, increased to 1 mg/kg/day during days 15-28, and tapered thereafter until discontinuance on day 194. Low CsA trough levels occurred in 15 patients (54%) during the i.v. administration period. Ten patients (36%) developed grade I and 3 patients (11%) developed grade II acute GVHD; there were no cases of grade III or IV disease. The actuarial incidence of chronic GVHD was 29% at 1 year but 57% at 2 years due to development of chronic GVHD after discontinuation of immunosuppressive agents. High blood CsA concentrations in stable outpatients led to dose-limiting nephrotoxicity. Infections occurred throughout the period of extended immunosuppression (from 6 to 12 months) but were not life-threatening. The actuarial incidence of leukemic relapse was 18% at 1 year and 25% at 2 years. Actuarial survival at 1 and 2 years was 68 and 51%, respectively. Despite the frequent occurrence of low CsA trough levels, this regimen appeared to be effective in preventing acute GVHD. Immunosuppressive prophylaxis beyond 1 year may be required to reduce late-onset chronic GVHD.

Adolescent↗

PubMed1995

Enhancement of monocytopoiesis by granulocyte colony-stimulating factor: evidence for secondary cytokine effects in vivo.

Granulocyte colony-stimulating factor (G-CSF) is used with increasing frequency to reduce the neutropenic interval following dose-intensive chemotherapy. In mice, exogenous G-CSF reduces neutrophil recovery after 5-fluorouracil (5-FU) treatment from 14 to 8 days. G-CSF treatment also enhances recovery of blood monocytes; colony assays show increased numbers of macrophage and granulocyte-macrophage progenitors (CFU-M and CFU-GM) in the marrow. This unexpected effect of G-CSF treatment is dependent on endogenous M-CSF; antiserum to murine M-CSF inhibits both peripheral monocyte and monocytic progenitor recovery without affecting neutrophil or CFU-GM recovery. Conversely, the effect of M-CSF depletion is seen only in G-CSF-stimulated recovery; monocyte levels in mice treated with antiserum to M-CSF after 5-FU are indistinguishable from mice given 5-FU alone. No synergy between G-CSF and M-CSF can be demonstrated in vitro with either normal or 5-FU-treated marrow, indicating this G-CSF/M-CSF interaction must be indirect. These results reveal an unpredicted beneficial effect of G-CSF treatment on monocyte recovery and a role for endogenous M-CSF in rebound hematopoiesis.

Animals↗

PubMed1995

Cyclophosphamide-mobilized peripheral blood stem cells in patient with lymphoid malignancies.

Mobilization of peripheral blood stem cells (PBSC) can be accomplished with cytokines or rebound from myelo-suppressive chemotherapy. In this study, patients were mobilized with cyclophosphamide (CY) 4 g/m2 either alone or followed by GM-CSF 250 micrograms/m2 or G-CSF 600 micrograms. Colony-stimulating factors were administered subcutaneously. Eligibility included patients with non-Hodgkin's lymphoma (NHL; n = 29), Hodgkin's disease (n 4) and acute lymphoblastic leukemia (n = 2). One patient died from mobilization-related complications. Admission for neutropenic fevers and other complications occurred in 73% of patients receiving CY alone compared with 32% received CY + G-CSF or GM-CSF (P < 0.05). Apheresis was initiated when the white blood count approached 1 x 10(9)/l and continued until approximately 6 x 10(8) mononuclear cells/kg were collected. Mobilization with CY + GM-CSF led to significantly greater numbers of collected CFU-GM than with CY alone. Colony-stimulating factors were not administered after transplantation. collected progenitor cells correlated with the peak cell counts after mobilization. Following transplantation, an ANC > = 500 x 10(6)/l was achieved at 14.5 days and a platelet count > = 50 x 10(6)/l was achieved on day 20. Days to achieve an ANC > = 500 x 10(6)/l did not correlate with any of the analyzed variables. Platelet engraftment correlated with harvested BFU-E, thawed CD34+ cells and peak counts following mobilization. for patients with NHL, CR was obtained in 82% of evaluable cases. Median time to relapse was 343 days. Twenty five per cent of patients remain disease-free at 900+ days of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1995

Late graft failure due to dual bone marrow infection with variants A and B of human herpesvirus-6.

Hematopoietic effects of human Herpesvirus-6 (HHV-6) infection following bone marrow transplantation (BMT) include delayed engraftment and early myelosuppression. Variant A has not been isolated after BMT. A case of graft failure is reported following an HLA-identical BMT for chronic myelogenous leukemia (CML) in chronic phase. Evaluation of bone marrow during the period of graft failure revealed variants A and B of HHV-6 by culture, immunofluorescence, polymerase chain reaction (PCR), and immunohistochemistry. Evidence for other cases of graft failure, including cytomegalovirus (CMV), could not be found. A hypothesis is proposed that late graft failure in this case was due to variant A of HHV-6.

Adult↗

PubMed1995

Bone marrow transplant-associated thrombotic microangiopathy: a case series.

Bone marrow transplant-associated thrombotic microangiopathy (BMT-TM) has been reported with widely varying frequencies and outcomes. Therefore a BMT-TM grading system (0-4) was developed based on the lactate dehydrogenase (LD) level and percentage (%) fragmented cells (FC) as follows: grade 0, normal or increases LD and FC < or = 1.2%; grade 1, normal LD and FC > or = 1.3%; grade 2, increases LD and FC = 1.3-4.8%; grade 3 increases LD and FC = 4.9-9.6%; and grade 4, increases LD and FC > or = 9.7%. Patients with grade 0 and grade 1 BMT-TM did not differ in clinical parameters. Twenty two patients had BMT-TM grade 2-4. These were observed for outcome. Seven of 10 with grade 2 BMT-TM had resolution of BMT-TM a median of 99 days (range 50-229 days) from diagnosis. This occurred spontaneously in five and following discontinuance of cyclosporine (CsA) in two. The remaining three had persistent BMT-TM at grade 2 (two patients) and grade 1 (one patient). In contrast, none with grade 3-4 BMT-TM had resolution. Seven with grades 3-4 BMT-TM underwent a variety of plasma exchange procedures; six had partial hematologic responses. Patients with grades 3-4 BMT-TM had a poorer survival (median survival = 60 days) than those with grade 2 BMT-TM where the median survival has not been reached (P = 0.018). These results indicate that BMT-TM is common following allogeneic-BMT and the outcome is dependent on the grade. Those with grade 1-2 BMT-TM generally do well.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1994

Phase I study of recombinant interleukin-1 beta in patients undergoing autologous bone marrow transplant for acute myelogenous leukemia.

A phase I trial was conducted with recombinant human interleukin-1 beta (rhIL-1 beta) in patients undergoing autologous bone marrow (BM) transplantation for acute myelogenous leukemia. rhIL-1 beta was administered at 3 dose levels (0.01, 0.02, 0.05 microgram/kg) by 30 minute intravenous infusion once a day beginning on the day of BM infusion and continuing for a total of 5 doses. A total of 17 patients were entered on the trial, and their results were compared with those of 74 consecutive historical control patients that did not receive colony stimulating factors. Moderate toxicity was observed in all patients. All 17 patients developed fever and chills within 30 minutes after initiation of rhIL-1 beta, and hypotension was observed in 14 of 17 patients 5 to 8 hours after the infusion. A total of 30% of patients required therapy (normal saline or dopamine) for treatment of hypotension. Therefore, dose escalation was discontinued at the 0.05 microgram/kg dose level. The number of days required to achieve an absolute neutrophil count greater than 500 mL in patients who received rhIL-1 beta was less than in historical patients (25 v 34; P = .02). This appeared to correlate with a reduced incidence of infection between days 0 and 28 after BM infusion (12% v 23%; P = .049). Median bilirubin, median creatinine, platelet recovery, and days in the hospital were not different between study patients and historical controls. Survival of patients who received rhIL-1 beta compared with that of historical patients was improved (30% v 20%; P = .04). These possible benefits were achieved at the cost of moderate toxicity during rhIL-1 beta administration.

Adolescent↗

PubMed1994

Human MCF activates monocytes to produce IL-1 but not TNF or CSF-1.

Monocyte cytotoxicity inducing factor (MCF) is a novel cytokine which was originally characterized by its ability to induce monocyte cytotoxicity against tumor targets. The present studies were undertaken to define the mechanisms of cytotoxicity. Since the cytotoxic state may be mediated, in part, by the secretion of monokines, MCF's effect on IL-1, TNF and CSF-1 were measured. MCF caused human peripheral blood monocytes to secrete large amounts of IL-1 but not TNF. In contrast monocytes produce CSF-1 in culture and this production was not enhanced by MCF. IL-1 neither appeared to directly lyse the target K562 nor was able to activate macrophages for cytotoxicity. However, IL-1 may be necessary for lysis of K562 by activated macrophages through its cytostatic effect on K562. MCF increased monocyte surface expression of DR-beta (when studied by fluorescent microfluorometry) and messenger RNA for DR-beta after 24 h in culture. These functional studies indicate that MCF is a cytokine with a distinct spectrum of biologic activities whose functions may be mediated by synthesis and secretion of IL-1.

Cytokines↗

PubMed1994

alpha-Interferon in myelofibrosis: a case report.

A patient with advanced myeloid metaplasia was treated with alpha-interferon (29 months) with a remarkable response. He had anaemia, thrombocytopenia and hepatosplenomegaly with infarction. The initial bone marrow showed replacement with fibrosis with no evident haemopoietic cells. Post-therapy, the patient became asymptomatic, transfusion independent and had normal blood counts. The repeat bone marrow was 30% cellular with 1 + reticulin and no fibrosis. Treatment was well tolerated without appreciable side-effects. These results indicate that prolonged therapy with alpha-interferon can improve haemopoiesis and reverse marrow fibrosis.

Biopsy, Needle↗

PubMed1994

Engraftment with peripheral blood stem cells using noncontrolled-rate cryopreservation: comparison with autologous bone marrow transplantation.

Peripheral blood stem cells (PBSC) are used increasingly as a source of stem cell support following myeloablative therapy. In this report, the results of 33 patients undergoing PBSC transplantation were compared to 17 concurrent patients undergoing autologous bone marrow transplantation (ABMT). PBSC were cryopreserved using 6% pentastarch and 5% dimethyl sulfoxide (DMSO) with noncontrolled-rate freezing. Many patients in the PBSC group were selected because they were excluded as candidates for ABMT due to prior pelvic irradiation, marrow tumor involvement, or other factors. PBSC were mobilized with high-dose cyclophosphamide (CY), CY+granulocyte-macrophage colony-stimulating factor (GM-CSF), or GM-CSF alone. Colony-stimulating factors were not administered after transplantation. A median of 7.4 x 10(8) mononuclear cells (MNC)/kg were collected containing a median of 3.2 x 10(4) granulocyte-macrophage colony-forming units (CFU-GM)/kg and 5.7 x 10(4) burst-forming units (BFU-E)/kg. After thawing, CFU-GM recovery was 67% and BFU-E recovery was 59%. The thawed, pooled PBSC contained 6.4 x 10(6) CD34+ cells/kg. The entire PBSC volume (median 870 mL) was infused over a median of 157 minutes. PBSC patients required a median of 15 days to achieve an ANC of 500/microL and 22 days for a platelet count of 50,000/microL. Neutrophil recovery was inversely correlated with the number of harvested progenitor cells (p = 0.014); the time to achieve a platelet count of 50,000/microL was inversely associated with CD34+ cells/kg (p = 0.005). PBSC transplant patients achieved an ANC of 500/microL 6 days faster (p < 0.05) and had a 10-day shorter hospitalization (p < 0.05) than ABMT patients. Use of noncontrolled-rate cryopreserved PBSC is associated with faster engraftment and shorter hospital duration than ABMT.

Adolescent↗

PubMed1993

Fluconazole prophylaxis of fungal infections in patients with acute leukemia. Results of a randomized placebo-controlled, double-blind, multicenter trial.

OBJECTIVE: To evaluate the efficacy and safety of fluconazole for prevention of fungal infections. DESIGN: A randomized, placebo-controlled, double-blind, multicenter trial. PATIENTS: Adults (257) undergoing chemotherapy for acute leukemia. INTERVENTION: Patients were randomly assigned to receive either fluconazole (400 mg orally once daily or 200 mg intravenously every 12 hours) or placebo. The study drug was started at initiation of chemotherapy and continued until recovery of neutrophil count, development of proven or suspected invasive fungal infection, or the occurrence of a drug-related toxicity. MEASUREMENTS: Fungal colonization, proven superficial or invasive fungal infection, empiric antifungal therapy with amphotericin B, drug-related side effects, and mortality. MAIN RESULTS: Fluconazole decreased fungal colonization (83 of 122 [68%] placebo patients compared with 34 of 119 [29%] fluconazole patients colonized at end of prophylaxis, P < 0.001) and proven fungal infections (27 of 132 [21%] placebo patients compared with 11 of 123 [9%] fluconazole patients infected, P = 0.02). Superficial fungal infections occurred in 20 of 132 (15%) placebo patients but in only 7 of 123 (6%) fluconazole patients (P = 0.01), whereas invasive fungal infections developed in 10 of 132 (8%) placebo patients and in 5 of 123 (4%) fluconazole patients (P = 0.3). Fluconazole was especially effective in eliminating colonization and infection by Candida species other than Candida krusei (66 of 122 [64%] placebo patients colonized at end of prophylaxis compared with 11 of 119 [9%] fluconazole patients, P < 0.001; 22 of 132 [17%] placebo patients infected compared with 7 of 123 [6%] fluconazole patients, P = 0.005). Aspergillus infections were infrequent in both fluconazole (3 cases) and placebo groups (3 cases). The use of amphotericin B, the incidence of drug-related side effects, and overall mortality were similar in both study groups. CONCLUSION: Prophylactic fluconazole prevents colonization and superficial infections by Candida species other than Candida krusei in patients undergoing chemotherapy for acute leukemia and is well tolerated. Fluconazole could not be clearly shown to be effective for preventing invasive fungal infections, reducing the use of amphotericin B, or decreasing the number of deaths.

Acute Disease↗

PubMed1993

Increased macrophage colony-stimulating factor levels in immune thrombocytopenic purpura.

Thrombocytopenia is a dose-limiting toxicity of macrophage colony-stimulating factor (M-CSF) in preclinical and initial phase I trials. Modulation of macrophage-mediated platelet destruction in immune thrombocytopenic purpura (ITP) may be affected by M-CSF activity. In this study, plasma levels of M-CSF were determined by a sensitive radioimmunoassay in 23 patients with ITP. These were compared with control levels measured in 24 healthy subjects. M-CSF levels were significantly higher in the ITP patients than in the control subjects (218 v 179, P < .02); however, there was a great deal of overlap. The highest M-CSF levels (median = 299 U/mL) were observed in three patients with Evan's syndrome. Patients with severe ITP (platelets < 25,000/microL) had intermediate M-CSF levels (median = 231 U/mL) and those with mild thrombocytopenia (> 25,000/microL) had normal levels (median = 173 U/mL). Sixteen patients were treated with corticosteroids: 10 responded and 6 did not. Median M-CSF levels were higher in those who failed to respond compared with responders (272 v 202, P < .05). These findings suggest M-CSF may influence macrophage-mediated platelet destruction in ITP.

Adolescent↗

PubMed1993

Effectiveness of cryosupernatant therapy in refractory and chronic relapsing thrombotic thrombocytopenic purpura.

This report describes objective improvement in two patients with poorly responsive thrombotic thrombocytopenic purpura (TTP) syndromes (with cryosupernatant). The first had a partial response to plasma exchange with whole plasma (fresh frozen plasma; FFP) and responded dramatically when switched to plasma exchange with cryosupernatant replacement. The second had chronic TTP (three relapses in 9 months) that required prolonged courses of exchange with FFP (approximately 1 month each) to achieve remission. Attempts to manage her recurrent TTP with infusion of two units of FFP had been unsuccessful. The latter patient was tried on cryosupernatant infusions (2 units daily) and responded within 4 days. Moreover, she has been in continuous remission for 12 months while receiving 2 units (one to three times per week). These results suggest that cryoprecipitate-poor plasma may offer advantages over whole plasma in the management of both acute and chronic forms of TTP.

Chronic Disease↗

PubMed1993

Recombinant human erythropoietin (rHuEPO) for treatment of myelodysplastic syndrome.

Sixteen patients (ages 53 to 85) with myelodysplastic syndrome (MDS) were treated with recombinant human erythropoietin (rHuEPO) to observe its effects on hematopoiesis. All were transfusion dependent and had Hb levels less than 9.0 g/dl and less than 10% marrow blasts. Eight patients had refractory anemia (RA), one had refractory anemia with excess blasts (RAEB), and seven had refractory anemia with ringed sideroblasts (RARS). A response was defined as an increase in Hb by greater than 2 g/dl and/or a decrease in transfusion requirement by greater than 50%. Patients were considered to be evaluable if on study greater than two months. Three of thirteen evaluable patients had a response. One patient with RA had a sustained trilineage hematologic response with no evidence of disease progression. None of the patients had trouble with hypertension or with thrombotic events. This suggests than an occasional patient with MDS will respond to rHuEPO. In some patients, this may be beneficial clinically.

Aged↗