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Biomedical subjects

R E Champlin

Publications and source records attributed to R E Champlin.

At least 91 records · Page 5Linked to original sources

Survival of patients with chronic myelogenous leukaemia relapsing after bone marrow transplantation: comparison with patients receiving conventional chemotherapy.

Treatment with busulphan and/or hydroxyurea rarely produces remission in patients with chronic myelogenous leukaemia (CML) in chronic phase. HLA-identical sibling transplants almost always produce remission, and only about 20% of patients relapse post-transplant. The increased anti-leukaemic efficacy of transplants results from intensive pretransplant treatment and immune-mediated anti-leukaemia effects. We studied 433 patients surviving > or = 2 years after diagnosis of CML to determine if patients who have relapsed after a transplant in chronic phase have longer survival from diagnosis than comparable subjects receiving chemotherapy. The chemotherapy cohort included 344 adults < 50 years of age treated on consecutive trials of the Italian Cooperative Study Group on CML between 1973 and 1986. The transplant cohort included 89 patients reported to the International Bone Marrow Transplant Registry who relapsed after an HLA-identical sibling bone marrow transplant carried out between 1978 and 1992. Survivals in the two groups were compared using Cox proportional hazards regression to adjust for prognostic variables. Median survival was 65 months in the chemotherapy cohort and 86 months in the transplant cohort. The 7-year probability (95% confidence interval) of survival was 34% (28-39%) in the chemotherapy cohort and 57% (43-70%) in the transplant cohort (P=0003). There was no difference in survival of patients relapsing after T-cell depleted and non-T-cell-depleted transplants. We conclude that patients who relapse after an HLA-identical sibling bone marrow transplant for CML in chronic phase have longer survival from diagnosis than comparable patients receiving chemotherapy. This effect is most likely to be the result of intensive chemotherapy and/or radiation given for pretransplant conditioning.

Adolescent↗

Impact of selection process on response rate and long-term survival of potential high-dose chemotherapy candidates treated with standard-dose doxorubicin-containing chemotherapy in patients with metastatic breast cancer.

PURPOSE: Most of the data about high-dose chemotherapy (HDCT) for metastatic breast cancer are derived from phase II studies. The interpretation of these data depends on comparisons with data from properly selected historical control patients treated with standard therapy under similar circumstances. We report the long-term results of patients with metastatic breast cancer who were eligible for HDCT but were treated with doxorubicin-containing standard-dose chemotherapy. PATIENTS AND METHODS: Prospectively collected data from 18 successive doxorubicin-containing protocols for the treatment of metastatic breast cancer were evaluated. Using common eligibility criteria for HDCT, we identified patients who would have been candidates for HDCT. We analyzed response rates, progression-free survival (PFS), and overall survival (OS) for all patients, potential HDCT candidates, and noncandidates. RESULTS: A total of 1,581 patients was enrolled onto the 18 studies. Six hundred forty-five were HDCT candidates, and 936 were noncandidates. The complete response rate was 27% for HDCT candidates and 7% for noncandidates; median PFS was 16 and 8 months and median OS was 30 and 17 months, respectively. Survival rates for HDCT candidates and noncandidates, respectively, were 21% and 6% at 5 years and 7% and 2% at 10 years. CONCLUSION: This study suggests that encouraging results of single-arm trials of HDCT could partially be due to selection of patients with better prognoses and further stresses the importance of completing ongoing randomized trials of HDCT to assess the relative efficacy of HDCT in patients with metastatic breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Phase I pharmacokinetic study of multicycle high-dose carboplatin followed by peripheral-blood stem-cell infusion in patients with cancer.

PURPOSE: To examine the feasibility of escalating carboplatin area under the concentration-time curve (AUC), using dose predictions based on individual estimates of drug clearance, in a phase I trial of multicycle carboplatin, paclitaxel, and cyclophosphamide chemotherapy with peripheral-blood stem-cell (PBSC) replacement. PATIENTS AND METHODS: Forty-four patients (37 breast, seven ovarian) received 165 courses. Initial target carboplatin AUC was 10 mg/ml x min, with interpatient escalation in increments of 25%. Initial carboplatin dose estimates used creatinine clearance (CrCl) to estimate carboplatin clearance. Subsequent clearance and dose estimates were determined using a model incorporating Bayesian estimation and two measured carboplatin plasma ultrafiltrate concentrations. RESULTS: Median clearance was 80.5 mL/min/m2 (range, 41.6 to 131.8). Carboplatin doses up to 2,440 mg/m2 per course were administered without major extramedullary toxicity. Doses varied 2.6-fold at each exposure level. Using the Bayesian model, AUC was predicted with a mean accuracy of 101.2% (83% using CrCl). Ninety-six of 117 courses were within 25% of the target AUC. This model was less biased (0.15 v -2.35 mg/mL x min) and more precise (2.76 v 3.52) in predicting AUC compared with one using CrCl. Hematologic recovery was not prolonged with increasing exposure. The carboplatin maximum-tolerated systemic exposure (MTSE) was 13.3 mg/mL x min (level five). The dose-limiting toxicity was cardiac toxicity, which occurred at dose levels six and seven. CONCLUSION: Results demonstrate that (1) CrCl is a poor estimator of carboplatin clearance in this population, and (2) the use of a model incorporating limited sampling and Bayesian estimation improves the precision of carboplatin clearance estimation and is suitable for targeting carboplatin exposure in an ambulatory setting.

Ambulatory Care↗

Safeguarding the administration of high-dose chemotherapy: a national practice survey by the American Society for Blood and Marrow Transplantation.

Overdoses of high-dose chemotherapy before hematopoietic cell transplantation are serious adverse events, but their frequency and etiology are unknown. The American Society for Blood and Marrow Transplantation (ASBMT) conducted an anonymous national survey to identify errors in safety practices during the administration of high-dose chemotherapy. The questionnaire was returned from 115 (68%) of 170 hematopoietic transplant centers in the United States. Ninety-four of the programs were university or affiliated centers, 19 were community hospitals, and 41 were founded since 1990. A total of 7650 transplants were reported for 1994: 22% of the programs performed 1-20 transplants, 60% performed 21-100 transplants, and 18% performed more than 100 transplants. Fifteen of the 115 responding centers reported a total of 18 patients inadvertently given overdoses of cisplatin (n=3), carboplatin (n=2), busulfan (n=2), cytosine arabinoside (n=2), cyclophosphamide (n=2), interleukin-2 (n=2), or other agents (n=5) between 1989 and 1994. Cumulative drug doses given as a daily dose (six cases) and nursing infusion errors (six cases) were the most common errors. The estimated chemotherapy overdose error rate was 0.06%, or 6 cases/10,000 transplants, with 95% confidence limits of 0.03-0.11%. The overdose rate among more experienced centers in operation before 1990 was lower than that among newer centers (p < 0.01). Large centers (> 100 transplants performed in 1994) experienced errors at rates lower than those in medium-sized centers (21-100 transplants, p = 0.03). Although the number of events was small in this self-reporting survey, overdoses were noted in 13% of the responding centers, especially among more recently established units. Safety practices need to emphasize multidisciplinary checkpoints at the physician, pharmacist, nursing, and institutional levels. Based on these survey results, ASBMT recommendations for further safeguards for high-dose chemotherapy administration are proposed.

Adult↗

Neutropenias following allogeneic bone marrow transplantation: response to therapy with high-dose intravenous immunoglobulin.

Cytopenias following bone marrow transplantation may be severe and life-threatening. These have been described post-allogeneic Klumpp, 1991: Bone Marrow Transplant 8:159-171. or post-autologous bone marrow transplants Khouri et al., 1994: J Clin Oncol 12:748-758. as well as with peripheral blood stem cell transplantation Klumpp et al., 1992: Am J Hematol 41:215-217. It can be immune mediated, associated on occasions with graft-versus-host disease (GVHD) Anasetti et al., 1989: Blood 4:1054-1058; however, in most cases, the underlying mechanism is uncertain. The treatment of post-transplant cytopenias is not well established, and they are often refractory to immunosuppressive therapy with steroids. Herein we describe two cases of neutropenia after allogeneic bone marrow transplantation that improved after therapy with high-dose intravenous immunoglobulin.

Adult↗

Community respiratory virus infections among hospitalized adult bone marrow transplant recipients.

From 1 November 1992 through 1 May 1993 and from 1 November 1993 through 1 May 1994, we conducted a prospective surveillance study at the University of Texas M.D. Anderson Cancer Center (Houston) to evaluate the role of community respiratory virus infections in hospitalized adult bone marrow transplant (BMT) recipients, Respiratory secretions were obtained from all adult BMT recipients with acute respiratory illnesses. During these two winters, a community respiratory virus was isolated from 37 (36%) of 102 patients and 30 (26%) of 115 patients, respectively. Approximately half (49%) of these infections were due to respiratory syncytial virus (RSV); the remainder were due to influenza virus (18%), picornaviruses (18%), parainfluenza virus (9%), or adenovirus (6%). Fifty-eight percent of these infections were complicated by pneumonia, with an associated mortality of 51%. The pneumonias that complicated RSV infection were almost exclusively viral in origin and were associated with a mortality of 100% if not treated promptly with antiviral agents. In contrast, many of the pneumonias that complicated the other viral infections, such as influenza, appeared to be either self-limited viral pneumonias or secondary bacterial or fungal pneumonias. Community respiratory viruses are frequent causes of acute respiratory illnesses in adult BMT recipients hospitalized during the winter and are associated with substantial morbidity and mortality.

Adenovirus Infections, Human↗

Bone marrow transplants from HLA-identical siblings in advanced Hodgkin's disease.

PURPOSE: To determine the outcome of HLA-identical sibling bone marrow transplants in advanced Hodgkin's disease. PATIENTS AND METHODS: We reviewed the data on 100 consecutive patients with Hodgkin's disease who received HLA-identical sibling bone marrow transplants between April 1, 1982 and August 12, 1992, reported to the International Bone Marrow Transplant Registry (IBMTR). The median interval from diagnosis to transplant was 2.5 years (range, < 1 to 14). All had advanced disease. Eighty-nine of 100 patients were not in remission at the time of transplant. Fifty had pretransplant Karnofsky scores less than 90% and 27 had active infection in the week before transplant. Patients received a variety of conditioning regimens; 45 received total-body radiation. RESULTS: The 100-day probability of acute graft-versus-host disease (GVHD) was 35% (95% confidence interval [CI], 26% to 46%); the 3-year probability of chronic GVHD was 45% (95% CI, 31% to 59%). The 3-year probability of relapse was 65% (95% CI, 50% to 78%). The 3-year probability of survival was 21% (95% CI, 14% to 30%). The 3-year disease-free survival rate was 15% (95% CI, 9% to 24%). CONCLUSION: HLA-identical sibling bone marrow transplants have a limited role in advanced Hodgkin's disease.

Adolescent↗

Chemotherapy versus transplants for acute myelogenous leukemia in second remission.

The best therapy for persons with acute myelogenous leukemia (AML) in 2nd remission is unknown. Bone marrow transplants from an HLA-identical sibling are reported to be better than chemotherapy but this is controversial. The objective of the study was to compare 3-year leukemia-free survival (LFS) in comparable subjects receiving chemotherapy or a transplant. 485 persons with AML in 2nd remission were studied. The chemotherapy cohort included 244 persons treated on trials of the British Medical Research Council, Eastern Cooperative Oncology Group and MD Anderson Hospital. The transplant cohort included 257 persons transplanted worldwide and reported to the international Bone Marrow Transplant Registry (16 were also chemotherapy subjects.) Subjects were selected for comparable age and year of treatment. Preliminary analyses identified two factors correlated with LFS: age < or = or > 30 years and 1st remission duration < or = or > 1 year; subsequent analyses were partitioned accordingly. Three-year probabilities of treatment-related mortality with chemotherapy and transplants were 7% (95% confidence interval, 3-15%) vs 56% (49-63%). Three-year leukemia relapse probabilities were 81% (74-86%) vs 41% (33-49%). Three-year probabilities of LFS were 17% (12-23%) vs 26 (20-32%). Cohort analysis showed significantly higher LFS with transplants vs chemotherapy in persons < or = 30 years and 1st remissions > 1 year (41% (29-53%) vs 17% (7-32%); P = 0.017) and those in > 30 years with 1st remissions < or = 1 year (18% (9-29%) vs 7% (2-16%); P = 0.046). Others had comparable LFS with both treatments. These data indicate better LFS with HLA-identical sibling transplants than chemotherapy in some persons with AML in 2nd remission.

Adolescent↗

Peripheral blood progenitor cells: a replacement for marrow transplantation?

Peripheral blood progenitor cells (PBPCs) are an effective source of hematopoietic stem cells for autologous or allogeneic transplantation. Progenitors must be mobilized into the circulation to allow efficient collection. Some promising mobilizing regimens include the use of stem cell factor and growth factors such as interleukin-3, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor. Transplantation of PBPCs has several advantages over bone marrow transplantation: larger numbers of progenitors can be collected, general anesthesia and multiple bone marrow aspirations can be avoided, and hematologic recovery appears to be more rapid and predictable with PBPCs. The disadvantages of using PBPCs for transplantation include the costs of multiple aphereses and purging procedures, the requirement for a mobilizing regimen, and the necessity for vascular access. Several uncertainties remain regarding the transplantation of PBPCs, including the optimal dose and composition of cells for transplantation.

Antigens, CD34↗

Risk factors for hepatic veno-occlusive disease following HLA-identical sibling bone marrow transplants for leukemia.

The objective was to analyze risk factors for veno-occlusive disease of the liver (VOD) after allogeneic bone marrow transplantation. A cohort of 1717 recipients of HLA-identical sibling transplants for leukemia between 1988 and 1990, in 200 transplant teams worldwide, was studied. Patients were scored as having VOD if liver tissue showed typical histologic features or if they had all three of the following: (1) jaundice; (2) hepatomegaly and right upper quadrant abdominal pain; and (3) ascites and/or unexplained weight gain. Patients surviving more than 7 days post-transplant without histologic or any of these clinical features of VOD were classified as not having VOD. Patient-, disease- and transplant-related characteristics of 95 patients with VOD were compared to those of 1514 without VOD. Variables correlated with an increased risk of VOD were: pretransplant conditioning with busulfan and cyclophosphamide compared to total body radiation (relative risk (RR) 2.8; P < 0.0001), pretransplant fungal infection (RR 4.1; P = 0.011), pretransplant Karnofsky performance score < 90% (RR 1.9; P = 0.012), prior liver disease (RR 1.9; P = 0.05) and age > 20 years (RR 1.8; P = 0.05). In patients receiving radiation for conditioning, intravenous immune globulin decreased VOD risk (RR 0.26; P = 0.003). This analysis identifies risk factors for VOD. The data suggest several strategies for modifying transplant regimens to reduce VOD risk and which patients might be suitable subjects for trials of strategies of VOD prevention.

Acute Disease↗

Results with high-dose chemotherapy and unpurged autologous stem cell transplantation in 73 patients with chronic myelogenous leukemia: the MD Anderson experience.

The purpose of this study was to evaluate the effectiveness of unpurged autologous stem cell transplantation (ASCT) for chronic myelogenous leukemia (CML) and its impact on the survival of patients in first and late chronic phase (CML-CP) including those resistant to or unable to tolerate interferon alfa (IFN-alpha) therapy. Between 1982 and 1993, 73 patients with CML who underwent ASCT were evaluated. Twenty-eight patients had signs of transformation, 20 were in second or subsequent CP, 22 had CML-CP and had shown resistance to or were unable to tolerate IFN-alpha therapy, and there had Philadelphia (Ph) chromosome-negative CML. Survival of patients in CML-CP who underwent ASCT was compared to controls who were in first CP receiving INF-a therapy. Patients and controls were matched for age, decade of therapy, response to IFN-alpha therapy (resistance vs toxicity) and the time to ASCT (study group) vs time to resistance (control group). Nine 12% patients failed to achieve hematologic recovery, and five (7%) had early death secondary to toxicity. Twenty-seven (58%) patients who received transplants in advanced-stage CML and 18 (82%) transplanted in CML-CP achieved complete hematologic remission (CHR). The incidence of complete cytogenetic response was 10 and 14%, respectively. The median survival of these two groups of patients was 5 and 34 months, respectively (P < 0.001). However, the survival of patients in CML-CP was not significantly different from controls (34 vs 49 months; P = 0.17). We conclude that unpurged ASCT does not prolong the survival of patients in CML-CP who are resistant to IFN-alpha therapy. Progress in autotransplantation in CML might require innovative approaches to eradicate the leukemic cells from the autologous stem cells prior to transplants.

Adolescent↗

HLA-identical sibling bone marrow transplants vs chemotherapy for acute myelogenous leukemia in first remission.

There is controversy whether adults with acute myelogenous leukemia (AML) in first remission are best treated with chemotherapy or an HLA-identical sibling bone marrow transplant. We studied 1097 adults, 16-50 years old, with AML in first remission. Results of transplants from HLA-identical siblings reported to the International Bone Marrow Transplant Registry (IBMTR; n = 901) were compared with results of chemotherapy in comparable persons treated by the German AML Cooperative Group (GAMLCG; n = 196). Preliminary analyses identified subject- and disease-related variables differing between the cohorts and associated with treatment outcome within each cohort. We adjusted for these variables and differences in time-to-treatment in subsequent comparisons of treatment-related mortality, relapse, survival and leukemia-free survival (LFS). Five-year probability of treatment-related mortality was greater for transplants than chemotherapy (43% (95% confidence interval, 37-49%) vs 7% (3-11%); P< 0.0001). Five-year relapse probability was less for transplants than chemotherapy (24% (20-28%) vs 63% (55-71%); P< 0.0001). Five-year probability of survival was similar with transplants and chemotherapy (48% (43-53%) vs 42% (33-51%); P = 0.24). Five-year LFS probability was higher for transplants than chemotherapy (46% (42-50%) vs 35% (28-41%); P= 0.01). These data indicate that bone marrow transplants from HLA-identical siblings result in comparable survival but greater LFS than chemotherapy in adults with AML in first remission.

Adolescent↗

Allogeneic blood stem cell transplantation: peripheralization and yield of donor-derived primitive hematopoietic progenitor cells (CD34+ Thy-1dim) and lymphoid subsets, and possible predictors of engraftment and graft-versus-host disease.

Apheresis-derived hematopoietic progenitor cells have recently been used for allogeneic transplantation. Forty-one normal donors were studied to assess the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) (12 micrograms/kg/d) on the peripheralization of hematopoietic progenitor cells and lymphoid subsets. The white blood cell, polymorphonuclear cell (PMNC), and lymphocyte concentrations at the peak of rhG-CSF effect in the donor's peripheral blood (PB) exceeded baseline by 6.4-, 8.0-, and 2.2-fold, respectively. Corresponding concentrations of PB CD34+ cells and primitive subsets such as CD34+ Thy-1dim, and CD34+ Thy-1dim CD38- cells increased by 16.3-fold, 24.2-fold, and 23.2-fold, respectively in eight normal donors. The percentage of CD34+ Thy-1dim and CD34+ Thy-1dim CD38- cells among CD34+ cells increased as well, suggesting an additional peripheralization effect of rhG-CSF on primitive CD34+ subsets. The preapheresis PB CD34+ and CD34+ Thy-1dim cell concentrations were predictive of their corresponding apheresis yield per liter of donor blood processed PB lymphoid subsets were not significantly affected by rhG-CSF treatment. The mean apheresis-derived yield of CD34+, CD34+ Thy-1dim, and CD34+ Thy-1dim CD38- cells per kilogram of recipient body weight and per liter of donor blood processed was 48.9 x 10(4) (n = 41), 27.2 x 10(4) (n = 10), and 1.9 x 10(4) (n = 10), respectively. As compared with 43 single bone marrow (BM) harvest, the CD34+ cell yield of peripheral blood progenitor cell allografts of 41 normal donors exceeded that of BM allografts by 3.7-fold and that of lymphoid subsets by 16.1-fold (CD3+), 13.3-fold (CD4+), 27.4-fold (CD8+), 11.0-fold (CD19+), and 19.4-fold (CD56+CD3-). All PBPC allografts were cryopreserved before transplantation. The mean recovery of CD34+ cells after freezing, thawing, and washing out dimethylsulfoxide was 86.6% (n = 31) and the recovery of lymphoid subsets was 115.5% (CD3+), 121.4% (CD4+), 105.6% (CD8+), 118.1% (CD19+), and 102.4% (CD56+CD3-). All donors were related to patients: 39 sibling-to-sibling, 1 parent-to-child, and 1 child-to-parent transplant. Thirty-eight transplants were HLA fully identical, two transplants differed in one and two antigens. Engraftment occurred in 38 recipients; two patients died too early to be evaluated, and one patient did not engraft. The lowest CD34+ cell dose transplanted and resulting in complete and sustained engraftment was 2.5 x 10(6)/kg of recipient body weight. There was no significant correlation between the total number of CD34+ cells transfused and the time to reach PMNC >0.5 x 10(9)/L or platelets > 50 x 10(9)/L posttransplant, nor was there a correlation found between the total number of CD3+, CD4+, and CD8+ cells transfused and the development of acute graft-versus-host disease (GVHD). The actuarial probability of developing acute GVHD in 38 evaluable patients was 48%. In 13 patients followed longer than 100 days posttransplant, the actuarial probability of developing chronic GVHD was 66% (median follow-up, 264 days).

Adolescent↗

Bone marrow transplantation for Fanconi anemia.

Fanconi anemia is a genetic disorder associated with diverse congenital abnormalities, progressive bone marrow failure, and increased risk of leukemia and other cancers. Affected persons often die before 30 years of age. Bone marrow transplantation is an effective treatment, but there are few data regarding factors associated with transplant outcome. We analyzed outcomes of HLA-identical sibling (N = 151) or alternative related or unrelated donor (N = 48) bone marrow transplants for Fanconi anemia performed between 1978 and 1994 and reported to the International Bone Marrow Transplant Registry. Fanconi anemia was documented by cytogenetic studies in all cases. Patient, disease, and treatment factors associated with survival were determined using Cox proportional hazards regression. Two-year probabilities (95% confidence interval) of survival were 66% (58% to 73%) after HLA-identical siblings transplants and 29% (18% to 43%) after alternative donor transplants. Younger patient age (P .0001), higher pretransplant platelet counts (P = .04), use of antithymocyte globulin (P = .005), and use of low-dose (15 to 25 mg/kg) cyclophosphamide plus limited field irradiation (P = .009) for pretransplant conditioning and cyclosporine for graft-versus-host disease prophylaxis (P = .002) were associated with increased survival. Bone marrow transplants are effective therapy for Fanconi anemia. The adverse impact of increasing age and lower pretransplant platelet count on transplant outcome favors earlier intervention, especially when there is an HLA-identical sibling donor.

Adolescent↗

Hypermetaphase fluorescence in situ hybridization for quantitative monitoring of Philadelphia chromosome-positive cells in patients with chronic myelogenous leukemia during treatment.

Using Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) as a model, our aim has been to develop a molecular cytogenetic method of high resolution analysis for monitoring the frequency of cells with nonrandom chromosome rearrangements in the bone marrow of patients receiving treatment for hematologic malignancies. Long-term exposure (24 hours) of bone marrow cultures to colcemid (0.1 microgram/mL) maximized a high frequency of metaphase collection. Such preparations were subjected to fluorescence in situ hybridization (FISH) using a 5 Mb probe that overlapped the region of the translocation at chromosome 9q34. This detected the Ph translocation in the resultant large number of overly contracted chromosome spreads. The procedure was validated and verified by studying 70 double-blind marrow samples from patients in different stages of Ph+ CML and from patients with Ph- hematologic malignancies (controls). This hypermetaphase FISH (HMF) method clearly identified Ph+ metaphases and allowed the analysis of 500 hypermetaphases per sample in less than 1 hour after FISH. HMF (1) identified statistically significant differences between the frequencies of Ph+ cells in samples that differed by less than 4%; (2) resolved such differences among patient samples that were all judged 100% Ph+ by standard G-band cytogenetics (CG); (3) resulted in the reclassification of response status in 23% of the patients initially classified by CG; (4) recognized Ph+ cells in 16% of patients characterized as having a complete cytogenetic response and in one patient with an original diagnosis of Ph- CML; and in one patient with an original diagnosis of Ph- CML; and (5) was informative where insufficient metaphases were obtainable for analysis by CG. HMF appears to be uniquely suitable for monitoring the status of patients with CML receiving treatment. It should also be applicable for patients with any hematologic diseases where chromosomal alterations are known and appropriate FISH probes are available.

Azure Stains↗

Long-term outcome of aplastic anemia in adults treated with antithymocyte globulin: comparison with bone marrow transplantation.

The outcome of 155 adult aplastic anemia (AA) patients treated with antithymocyte globulin (ATG, Upjohn, Kalamazoo, MI) at University of California, Los Angeles from 1977 to 1988 was evaluated. The median survival of the 146 patients who did not undergo bone marrow transplantation was 5.6 years, with 49% +/- 4% surviving more than 6 years. The most important predictor of survival was positive response to ATG (P < 0.001), which was observed in 48% of patients. Among pretreatment variables, disease severity was the best predictor of survival. Patients with moderate AA (MAA) had significantly better survival than those with severe (SAA) or very severe (VSAA) disease (P = 0.04). The 6-year actuarial survival rates of the three groups were 71% +/- 9%, 48% +/- 7% and 38% +/- 7%, respectively. Cox regression analysis found disease severity to be the only pretreatment variable significantly associated with survival (P = .02). Patient age, sex, disease etiology, concurrent treatment with androgens, or duration of ATG therapy were not associated with differences in survival or response to ATG. Late clonal hematologic complications (ie, myelodysplasia, acute myelogenous leukemia) were observed in 5 of the 77 patients followed for more than 2 years after ATG treatment. In addition, one case of non-Hodgkin's lymphoma and three solid tumors occurred in the ATG-treated patients. The survival of 56 ATG-treated patients with SAA or VSAA between the ages of 16 and 43 did not differ significantly from that of 55 adult AA patients who underwent bone marrow transplant (BMT) during the same time period (P = 0.6). However, 6-year survival rates improved from 43% for patients transplanted before 1984, to 72% for those who underwent BMT between 1984 and 1989. In contrast, there was no difference in the survival rates of patients treated with ATG during these two time periods (46% v 45%, respectively). The results suggest a superior long-term outcome for adult patients with SAA treated with BMT rather than with ATG alone, using current protocols.

Adolescent↗

Principles of bone marrow processing and progenitor cell/mononuclear cell concentrate collection in a continuous flow blood cell separation system.

The application of continuous flow apheresis technology to processing bone marrow for collection of the mononuclear progenitor cell population appears to follow the same principles as collection of mononuclear cells from peripheral blood. Unlike peripheral blood, however, where mobilization of cells from extravascular sites during the procedures contributes significantly to the final cell yield, the entire quantity of progenitor cells available for recovery from marrow is present in the original marrow when it is pooled. The process then becomes one of attempting optimal recovery of the cells of interest while excluding contaminating erythrocytes and cells of the myeloid series. This study reports the development of a protocol for recovery of MNC, CD33+, CD34+, and CD34+/DR- cells from harvested marrow for autologous and allogeneic transplants using a continuous flow blood cell separator, the variables influencing the recovery of the cells of interest and the clinical response to infusion of the processed cells.

Antigens, CD↗