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F Appelbaum

Publications and source records attributed to F Appelbaum.

At least 19 recordsLinked to original sources
PubMed2005

Serious graft-versus-host disease after hematopoietic cell transplantation following nonmyeloablative conditioning.

The efficacy of allogeneic hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning depends on the balance between the desirable antineoplastic effects of donor cells weighed against the undesirable morbidity of graft-versus-host disease (GVHD). Development of serious acute or chronic GVHD was analyzed retrospectively in 171 consecutive patients, who had related or unrelated nonmyeloablative HCT for hematologic malignancies. GVHD was defined as serious when it resulted in (1) death, (2) disability, (3) three or more major infections in 1 year, (4) prolonged hospitalization or (5) suicide or hospitalization for suicidal ideation. According to this definition, 43 of 171 (25%) patients developed serious GVHD with a median follow-up of 30 (range, 12-65) months. The incidence of serious GVHD was similar after related and unrelated HCT. Among the 43 patients with serious GVHD, 20 had grade III-IV acute GVHD, and 30 had extensive chronic GVHD. Among the 171 patients, seven had grade III acute GVHD and 84 had extensive chronic GVHD that did not meet criteria for serious GVHD. Assessment of serious GVHD provides additional useful information to acute GVHD grades and classification of limited and extensive chronic GVHD in describing the overall risk and impact complications caused by donor cells.

Activities of Daily Living↗
PubMed2003

Autologous stem cell transplantation for Hodgkin's disease: busulfan, melphalan and thiotepa compared to a radiation-based regimen.

We evaluated prognostic factors and treatment outcome of patients with relapsed/refractory Hodgkin's disease (HD) receiving autologous stem cell transplantation (ASCT). In total, 92 patients received total body irradiation, cyclophosphamide and etoposide (TBI/CY/E) (n=42) or busulfan, melphalan and thiotepa (Bu/Mel/T) (n=50) supported with ASCT. A total of 33 (66%) patients receiving the Bu/Mel/T regimen had a prior history of dose-limiting irradiation. Mucositis, hepatic and pulmonary toxicities were the main causes of morbidity and mortality, irrespective of the conditioning regimen. The transplant-related mortality was 15%. With a median follow-up of 6 years (range 2.5-11), the cumulative probabilities of survival, event-free survival (EFS) and relapse at 6 years were 55, 51 and 32%. The 6-year Kaplan-Meier (KM) probabilities of EFS for patients with less advanced disease (patients in first chemotherapy-responsive relapse or second remission (n=42)) and more advanced disease (all other patients (n=50)) were 60 and 44%. No differences in toxicities and efficacy between the conditioning regimens were found. ASCT is an effective treatment for patients with refractory/relapsed HD. Female patients and patients with less advanced disease at transplant had a better outcome. Patients with prior irradiation benefited from the Bu/Mel/T regimen.

Adolescent↗
PubMed2003

Outcome following haematopoietic cell transplantation in patients with myelodysplasia and del (5q) karyotypes.

The deletion (5q) karyotype [del (5q)] in patients with myelodysplastic syndrome (MDS) is considered a good risk feature, while the impact of del (5q) combined with other karyotypic abnormalities [del (5q)+] is less well defined. We analysed the outcome of haematopoietic cell transplants (HCT) in patients with MDS with del (5q) or del (5q)+. Fifty-seven patients, aged 6-72 years, with MDS and del (5q) abnormalities received HCT from related (n = 32) or unrelated (n = 25) donors. By French-American-British (FAB) criteria, 27 patients had refractory anaemia (RA), 10 RA with excess blasts (RAEB), eight RAEB in transformation (RAEB-T) and 12 acute myeloid leukaemia evolving from MDS (tAML). Non-relapse mortality at 1-year post-transplantation was 30% for del (5q) and 38% for del (5q)+ patients. Relapse occurred in one of 20 del (5q) patients and 15 of 37 del (5q)+ patients (P = 0.001). After adjusting for del (5q) status, blast count (<5%) was the only factor significantly associated with relapse-free survival. Patients with del (5q), either as a '5q- syndrome' or with MDS in general, had better outcomes than did patients with del (5q)+. The indication for transplantation in patients with del (5q) was generally severe cytopenias, compared with disease progression to a more advanced FAB stage in patients with del (5q)+. Conceivably, outcome for patients with del (5q)+ would be improved with transplantation earlier in the disease course.

Acute Disease↗
PubMed2002

Soluble TNF receptor fusion protein (etanercept) for the treatment of myelodysplastic syndrome: a pilot study.

Blockade of tumor necrosis factor (TNF)alpha by a soluble TNF receptor fusion protein (etanercept; Enbrel) improved in vitro hemopoiesis from the marrow of patients with myelodysplastic syndrome (MDS). Therefore, we enrolled 14 MDS patients (4 RA, 2 RARS, 6 RAEB, 2 CMML), 44-80 (median 60) years old, in a pilot trial. Etanercept, 25 mg, was given twice a week s.c. for 16 weeks (increased to three times a week if no response at 8 weeks). Among 12 evaluable patients, four had rises in hemoglobin by 1-1.5 gm/dl (three) or decreased transfusion requirements (one). Two patients had increased platelet counts (54% and 73%), and two increased neutrophils (63% and 120%). Baseline TNFalpha levels, determined in all patients, did not correlate with responses. Among eight marrows available for sequential in vitro assays, four showed increases in CFU-GM of 1.5- to 5-fold at 8 weeks, whereas three showed 3- to 10-fold decrements relative to baseline. Thus, etanercept treatment resulted in moderate improvements of cytopenias in some patients, while cell counts declined in others. Additional trials are needed to evaluate its clinical efficacy in MDS.

Adult↗
PubMed2001

Haemopoietic stem cell transplantation for advanced polycythaemia vera or essential thrombocythaemia.

Ten patients with polycythaemia vera (PV) and nine with essential thrombocythaemia (ET) received a haemopoietic stem cell transplant (HSCT) at the Fred Hutchinson Cancer Research Center between May 1988 and March 2000. HSCT was performed because of progression to the spent phase of the disease with myelofibrosis and splenomegaly in 10 patients and evolution into a myelodysplastic syndrome (MDS) or acute myelogenous leukaemia (AML) in nine patients. Patients were 18-59 years old (median 43). The interval from diagnosis to HSCT was 77-300 months (median 170). Seven patients were splenectomized before transplantation, and all but five had been treated with cytotoxic agents. Eleven patients received a transplant from a related, and eight from an unrelated, donor following conditioning with chemotherapy only or chemotherapy plus total body irradiation regimens. All evaluable patients achieved sustained engraftment. Twelve patients are surviving 5-116 months (median 41) after transplant, 10 in continued complete remission, one in haematological remission with residual marrow fibrosis and one with mixed haemopoietic chimaerism currently receiving therapy with interferon. Seven patients (six with AML/MDS and one with myelofibrosis) died of transplant-related complications. These data show that HSCT can provide curative therapy for patients with PV and ET with advanced disease.

Adult↗
PubMed2000

Long-term follow-up of remission duration, mortality, and second malignancies in hairy cell leukemia patients treated with pentostatin.

The nucleoside analogue, pentostatin, has demonstrated high complete response rates and long relapse-free survival times in patients with hairy cell leukemia, a disease that historically had been unresponsive to treatment. Long-term data on duration of overall survival and relapse-free survival and incidence of subsequent malignancies with this agent are lacking. Patients completing the treatment phase of a randomized, intergroup study who received pentostatin as an initial treatment or who crossed over after failure of interferon alpha were followed for survival, relapse, and diagnosis of subsequent malignancies. Two hundred forty-one patients treated with pentostatin as initial therapy (n = 154) or who crossed over after failure of interferon alpha (n = 87) were followed for a median duration of 9.3 years. Estimated 5- and 10-year survival rates (95% confidence interval) for all patients combined were 90% (87%-94%) and 81% (75%-86%), respectively. In the 173 patients with a confirmed complete response to pentostatin treatment, 5- and 10-year relapse-free survival rates were 85% (80%-91%) and 67% (58%-76%), respectively. Survival curves for patients initially treated with pentostatin and those crossed over were similar. Only 2 of 40 deaths were attributed to hairy cell leukemia. The mortality rate and incidence of subsequent malignancies were not higher than expected in the general population. Pentostatin is a highly effective regimen for hairy cell leukemia that produces durable complete responses. Subsequent malignancies do not appear to be increased with pentostatin treatment.

Adult↗
PubMed2000

Treatment of chronic myelomonocytic leukaemia by allogeneic marrow transplantation.

We evaluated the outcome of allogeneic bone marrow transplantation (BMT) in 21 patients with chronic myelomonocytic leukaemia (CMML) who were treated at the Fred Hutchinson Cancer Research Center between 1990 and 1998. There were 11 male and 10 female patients with a median age of 47.4 years (range 1.0-62.9). Patients were conditioned either with total body irradiation (TBI) and chemotherapy, with or without antithymocyte globulin (n = 19), or with chemotherapy alone (n = 2). The marrow donor was an HLA-identical sibling in 12 patients, an HLA-non-identical related donor in three patients and an unrelated volunteer donor in six patients. All evaluable patients achieved sustained engraftment. Fifteen patients developed grades II-IV acute graft-versus-host disease (GVHD). Nine patients (43.0%) are surviving disease free at 0.7-8.1 years (median 6.9) after transplantation. Five patients relapsed 75-660 d after transplant and all died. Five patients died with organ failure and two died with GVHD and associated infections. The Kaplan-Meier estimates of disease-free survival and relapse at 3 years were 39% and 25% respectively. The probability of survival was improved in patients with shorter disease duration compared with those with a long interval from diagnosis to BMT. Thus, as with other myeloproliferative diseases or myelodysplastic syndromes, BMT offers curative therapy for a proportion of patients with CMML. We suggest that patients with CMML who have a suitable donor should be considered for transplantation, probably early in their disease course. However, it will be important to develop new regimens with enhanced antileukaemic efficacy without further increasing regimen-related toxicity and mortality.

Adolescent↗
PubMed1998

Bone marrow transplants from unrelated donors for patients with chronic myeloid leukemia.

BACKGROUND: Chronic myeloid leukemia can be cured by marrow transplantation from an HLA-identical sibling donor. The use of transplants from unrelated donors is an option for the 70 percent of patients without an HLA-identical sibling, but the morbidity and mortality associated with such transplants have been cause for concern. We analyzed the safety and efficacy of transplants from unrelated donors for the treatment of chronic myeloid leukemia and identified variables that predict a favorable outcome. METHODS: Between May 1985 and December 1994, 196 patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase received marrow transplants from unrelated donors. RESULTS: The median follow-up was 5 years (range, 1.2 to 10.1). Graft failure occurred in 5 percent of patients who could be evaluated. Acute graft-versus-host disease of grade III or IV severity was observed in 35 percent of patients who received HLA-matched transplants, and the estimated cumulative incidence of relapse at five years was 10 percent. The Kaplan-Meier estimate of survival at five years was 57 percent. Survival was adversely affected by an interval from diagnosis to transplantation of one year or more, an HLA-DRB1 mismatch, a high body-weight index, and an age of more than 50 years. Survival was improved by the prophylactic use of fluconazole and ganciclovir. The Kaplan-Meier estimate of survival at five years was 74 percent (95 percent confidence interval, 62 to 86 percent) for patients who were 50 years of age or younger who received a transplant from an HLA-matched donor within one year after diagnosis. CONCLUSIONS: Transplantation of marrow from an HLA-matched, unrelated donor is safe and effective therapy for selected patients with chronic myeloid leukemia.

Adolescent↗
PubMed1998

Reproducibility in retrospective grading of acute graft-versus-host disease after allogeneic marrow transplantation.

We have undertaken a formal study to evaluate the reproducibility of retrospective assessments for grading the severity of acute GVHD. Using criteria previously established by the Seattle group, three reviewers independently assigned GVHD severity grades for a set of 100 marrow transplant patients. Significant differences were found in the distribution of GVHD grades assigned by one of the reviewers as compared to the other two reviewers. In only 40% of cases did all three reviewers assign the same GVHD grade, and in only 68-71% of cases did all three reviewers assign the same grade within 0-I vs II-IV or 0-II vs III-IV categories. Despite the high rate of disagreement between any two reviewers, at least two reviewers assigned the same overall GVHD grade in 93% of cases. These results suggest that current criteria for assessing the severity of GVHD by a single reviewer are not sufficiently reliable for rigorous clinical studies. As an alternative to the original criteria, we have developed and tested simplified criteria that summarize the clinical course of GVHD as reflected by the progression of disease and the amount of immunosuppressive treatment used to control the disease. Our results suggest that the revised criteria might yield more reproducible retrospective grading than the original criteria. Although the original criteria and the revised criteria might produce different results for individual patients, the overall distributions of grades with the two systems were similar. The proposed revised criteria could be implemented without disrupting the continuity and consistency with previous grading assigned by the original criteria.

Bone Marrow Transplantation↗
PubMed1998

Isolation of CD34+ cells from blood stem cell components using the Baxter Isolex system.

The CD34 antigen is expressed by human hematopoietic progenitor and stem cells. These cells are capable of reconstituting marrow function after marrow-ablative chemo-radiotherapy. Several different technologies have been developed for the separation of CD34+ cells from bone marrow or peripheral blood stem cell (PBSC) components. We used an immunomagnetic separation technique to enrich CD34+ cells from PBSC components in anticipation of autologous transplantation for patients with B lymphoid malignancies. Twenty-nine patients enrolled on this study and received mobilization chemotherapy followed by G-CSF. Of these, 21 achieved a peripheral blood CD34+ cell level of at least 2.0 x 10(4)/l required by protocol for separation of the stem cell components. A median of three components per patient was collected for processing. The average CD34+ cell concentration in the components after apheresis was 1.0 +/- 1.2%. After the CD34+ cell selection, the enriched components contained 0.6 +/- 0.6% of the starting nucleated cells. The recovery of CD34+ cells, however, averaged 58.4 +/- 19.2% of the starting cell number, with a purity of 90.8 +/- 6.5%. Overall depletion of CD34- cells was 99.96 +/- 0.06%. Nineteen patients were treated with marrow-ablative conditioning regimens and received an average of 6.2 +/- 2.0 x 10(6) CD34+ cells/kg body weight. These patients recovered to an ANC >0.5 x 10(9)/l at a median of 11 days (range 8-14), and platelet transfusion independence at a median of 9 days (range 5-13). Four patients died of transplant-related complications or relapse before 100 days after transplantation. No patient required infusion of unseparated cells because of failure of sustained bone marrow function. These data demonstrate that peripheral blood-derived CD34+ cells enriched by use of an immunomagnetic separation technique are capable of rapid engraftment after autologous transplantation.

Adult↗
PubMed1998

Retrospective analysis of infectious disease in patients who received recombinant human granulocyte-macrophage colony-stimulating factor versus patients not receiving a cytokine who underwent autologous bone marrow transplantation for treatment of lymphoid cancer.

Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) significantly shortens the number of days required to achieve an absolute neutrophil count of >500/mm3 after autologous bone marrow transplantation (ABMT); however, the ability of rhGM-CSF to enhance neutrophil and macrophage function in vivo has been incompletely characterized. In this retrospective study, the authors compared the incidence of infection from the day of transplantation to 28 days posttransplantation between two groups of previously studied patients who underwent ABMT at the Fred Hutchinson Cancer Research Center. A control group that received no cytokine was compared with a study group that received rhGM-CSF while participating in phase I, II, or III trials. During the posttransplantation period when both study groups had severe neutropenia, 40% (38 of 95) of control patients were found to have an infection, whereas only 13% (6 of 46) of rhGM-CSF patients developed an infection (p = 0.001). Most infections occurred before an absolute neutrophil count of > 100/mm3 was achieved. There was a trend toward fewer fungal infections (14% vs. 4%; p = 0.093); gram-negative bacterial infections (6% vs. 0%; p = 0.083); pulmonary infections (12% vs. 2%; p = 0.062); fewer days of amphotericin B (p = 0.0305); and fewer days of intravenous antibiotics (p = 0.0791) in rhGM-CSF-treated patients. These results support in vivo findings that the function-enhancing effect of rhGM-CSF may reduce infection-related complications.

Adolescent↗
PubMed1997

Use of alpha-2a-interferon to treat cytogenetic relapse of chronic myeloid leukemia after marrow transplantation.

Fourteen patients with cytogenetic relapse of chronic myeloid leukemia (CML) after transplantation with unmanipulated bone marrow were treated with alpha-2a-interferon. There were eight men and six women, median age, 33 years. Twelve patients received marrow from a related allogeneic donor and two received marrow from a syngeneic donor. The median percentage of Ph-positive metaphases at the time of starting interferon was 55% (10% to 87%). Daily interferon was started at a dose of 1 to 3 x 10(6) U/M2/d, depending on initial blood counts and was adjusted as tolerated to maintain the white blood count in the range of 2,000 to 3,000/microL and the platelet count greater than 60,000/microL. After a stable cytogenetic remission was achieved, the interferon dose was decreased to a maintenance level. Twelve patients achieved a complete cytogenetic remission on at least one occasion. Median time to achieve a complete cytogenetic remission was 7.5 months (range, 1.5 to 12). Eight patients remain in cytogenetic remission for 10+ to 54+ months from the time of first documented remission. After complete cytogenetic remission was established, nine patients were tested for the presence of the mRNA transcript of the bcr/abl fusion gene by polymerase chain reaction (PCR) testing. Four patients were PCR-negative on at least one occasion: two patients were PCR-negative on a single occasion; one patient had serial tests, which were PCR-negative; and one patient had serial PCR-negative peripheral blood tests with a single PCR-positive bone marrow obtained concurrently with a negative peripheral blood test. Median follow-up time for all patients is 44 months (range, 20 to 64). Interferon was generally well tolerated; only one responding patient was unable to continue interferon because of toxicity. Interferon induces durable cytogenetic remissions in a significant proportion (57%) of patients with cytogenetic relapse following bone marrow transplantation (BMT) without causing life-threatening toxicities.

Adolescent↗
PubMed1995

Factors that influence collection and engraftment of autologous peripheral-blood stem cells.

PURPOSE: To analyze factors that affect the collection of peripheral-blood stem cells (PBSC) before transplant and the tempo of engraftment after transplant. PATIENTS AND METHODS: A consecutive series of 243 patients with breast cancer (n = 87), malignant lymphoma (n = 90), multiple myeloma (n = 32), or other malignancies (n = 34) had PBSC collected following stimulation with colony-stimulating factors (CSFs) or after chemotherapy followed by CSF. Infusion of PBSC was performed following myeloablative chemotherapy with chemotherapy with or without total-body irradiation (TBI). Postinfusion CSFs were administered to 72 patients. An analysis of factors that influence CD34+ cell yield was performed by linear regression. Cox regression analysis was used to determine factors that affect the kinetics of granulocyte and platelet recovery following infusion of PBSC. RESULTS: Mobilization with chemotherapy followed by CSF, a diagnosis of breast cancer, absence of marrow disease, no prior history of radiation therapy, and fewer cycles of conventional-dose chemotherapy were associated with a higher average daily yield of CD34+ cells. In the multivariate analysis, the CD34 content of infused cells and the use of a posttransplant CSF influenced neutrophil recovery after infusion of PBSC. CD34 content was also important for predicting platelet recovery. The use of postinfusion CSF was associated with a significant delay in platelet recovery in patients who received less than 5.0 x 10(6) CD34+ cells/kg, but there was no discernable effect in patients who received greater than 5.0 x 10(6) CD34+ cells/kg. CONCLUSION: Disease status and prior treatment influence the ability to mobilize PBSC. CD34 cell dose is an important predictor of engraftment kinetics after PBSC transplant, regardless of disease or mobilization technique. The use of postinfusion CSF improves neutrophil recovery, but at low CD34 doses can delay platelet recovery.

Adolescent↗
PubMed1995

Phase III randomized, double-blind placebo-controlled trial of rhGM-CSF following allogeneic bone marrow transplantation.

Preliminary studies in allogeneic BMT suggest that recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) is well tolerated. This is a prospective, multicenter, randomized, double-blind, placebo-controlled trial. Yeast-derived rhGM-CSF 250 micrograms/m2/day or placebo was administered by 4-hour i.v. infusion starting on the day of marrow infusion (day 0) to day 20. All patients received HLA-identical sibling marrow and cyclosporine and prednisone for GVHD prophylaxis. Fifty three patients received rhGM-CSF and 56 received placebo. Comparison of demographics revealed no differences. The time to achieve an absolute neutrophil count of > 0.5 x 10(9) cells/l was shortened in rhGM-CSF treated patients (day 13 vs. 17, P = 0.0001). The incidences of grade III-IV mucositis and infection were significantly reduced (P = 0.005, P = 0.001, respectively) and duration of hospitalization was modestly shortened by 1 day (P = 0.02) in rhGM-CSF treated patients. No differences in platelet recovery, erythrocyte recovery, incidence of veno-occlusive disease, GVHD severity, relapse or survival were observed. In conclusion, rhGM-CSF is well tolerated and reduces post-transplant morbidity in patients undergoing HLA-identical allogeneic BMT.

Adult↗