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Biomedical subjects

G Elfenbein

Publications and source records attributed to G Elfenbein.

At least 19 recordsLinked to original sources

Syngeneic hematopoietic stem cell transplantation for women with metastatic breast cancer.

Metastatic breast cancer has been a common indication for autologous hematopoietic stem cell transplantation (HSCT). Previous reports indicate 3-year survival and progression-free survival (PFS) rates after autotransplant to be about 30 and 15%, respectively. Most deaths are from recurrent disease. One potential cause for high relapse rates is graft contamination with tumor. We describe 14 women with metastatic breast cancer transplanted between 1991 and 1998 with hematopoietic cells from identical twins. Median age was 41 y (range 34-50). Most women (12 of 14) were treated with mastectomy, and all received anthracycline-based regimens in their pretransplant course; nine women also received a taxane, seven radiotherapy and three hormonal therapy. Four women were in complete remission (one CR, three CRU) at transplant, five were in partial remission, two had stable disease and two had progressive disease. Eight women have died, one of treatment-related causes and seven of progressive breast cancer. Three-year survival was 48% (21-71%) and 3-year PFS was 21% (5-45%). Although the number of patients is small, outcomes for women transplanted with syngeneic grafts are similar to those of women receiving autologous grafts. This suggests that residual cancer in the patient is the major contributor to relapse after transplantation for breast cancer.

Adult↗

Improved survival of patients with chronic myelogenous leukemia undergoing allogeneic bone marrow transplantation.

A total of 28 patients with chronic myelogenous leukemia (CML) in chronic phase (CP) received bone marrow allografts from HLA-matched siblings at the University of Florida between August 1984-July 1992. The present study compares the disease-free survival (DFS) for those patients who were transplanted before or after August 1988 using the same conditioning regimen. The analysis shows significant difference in 3-year DFS for those patients transplanted post- vs. pre-August 1988 (69.6% vs. 20%, respectively; P = 0.006). A decrease in pneumonitis due to different etiologies from pre-August 1988 (6/13, 46%) to post-August 1988 (1/15, 7%) was statistically significant (P = 0.029). A decrease, although statistically insignificant, in the overall incidence and severity of acute and chronic graft vs. host disease (GVHD) after August 1988 was also noticed. This study indicates significantly improved outcome for patients with CML in CP who have been treated in the University of Florida after August 1988. Better supportive care and prophylaxis for GVHD most likely contributed to such improvement.

Adult↗

The platelet-refractory bone marrow transplant patient: prophylaxis and treatment of bleeding.

Refractoriness to platelet transfusions remains a significant problem for oncology patients, occurring in 30% to 70% of multiply transfused recipients with bone marrow failure. Nonimmune causes are often present and include disseminated intravascular coagulation, concurrent use of amphotericin B, infection, presence of palpable spleen, use of antibacterial antibiotics, bleeding, veno-occlusive disease, and fever. Immune causes are also commonly responsible for refractoriness, with HLA alloimmunization dominating the list of immune factors. HLA antibodies can be identified in 25% to 30% of transfused leukemia patients and can be present in as many as 80% of aplastic anemia patients. Developing a consistent approach to managing these refractory patients is essential to preventing and treating bleeding manifestations. An HLA type should be obtained for all patients anticipated to have chronic transfusion requirements. Screening for lymphocytotoxic antibodies can confirm suspected HLA alloimmunization. Histocompatible platelets (cross-match compatible and HLA matched) should be provided for all patients with HLA antibodies. A number of other therapeutic modalities have been used in an effort to manage the alloimmunized patient; most of these methods have had little or no proven benefit. When bleeding develops in the alloimmunized patient, there are few therapeutic choices. If histocompatible platelets are unavailable or unsuccessful, massive platelet transfusions of pooled platelet concentrates are commonly used, although this practice is of no proven benefit. While antifibrinolytic agents have been available for over 30 years, they are only recently being applied to control bleeding in chronic thrombocytopenia. We have successfully managed bleeding episodes in thrombocytopenic bone marrow transplant recipients with the use of epsilon aminocaproic acid. A number of these patients were platelet refractory with demonstrable platelet antibodies. Platelet refractoriness continues to plague multiply transfused oncology patients. While preventative measures may ultimately benefit some patients, this problem will continue to manifest itself. A consistent approach to transfusion support needs to be implemented to best manage this challenging patient population.

Aminocaproic Acid↗

Myeloablative chemoradiotherapy and autologous bone marrow infusions for treatment of neuroblastoma: factors influencing engraftment.

Bone marrow harvested from cancer patients for autologous bone marrow reinfusion (ABMR) after myeloablative treatment may be injured, in both its proliferating and stromal cell pools, by either previous treatment or manipulation at the time of harvest. We have examined the relative effects of seven covariates on hematologic recovery after ABMR in children with neuroblastoma (NBL) using univariate and step-up analysis. We measured recovery by times to achieve (1) white blood cell counts greater than 1,000/microL; (2) absolute neutrophil counts greater than 500/microL; and (3) platelet counts greater than 20,000/microL without transfusion. In univariate analysis, recovery was significantly associated with the amount of prior chemotherapy and the interval between last chemotherapy and marrow harvest. Patient sex, the number of granulocyte-macrophage colonies infused, harvest-to-freeze interval, and use of purging were marginally associated. After adjusting for potential confounders in a multivariate model, the amounts of chemotherapy and granulocyte-macrophage colonies infused were independently significant predictors of time to total white blood cell count recovery; chemotherapy courses and chemo-to-harvest interval were predictors of neutrophil count recovery; and sex, use of purging, and harvest-to-freeze interval were marginal predictors of platelet recovery. The speed of hematologic recovery after ABMR seems to depend mainly on pre-existing factors and marginally on manipulation of the marrow after harvest. These factors may affect both proliferating and stromal cell pools.

Antineoplastic Combined Chemotherapy Protocols↗

High-dose chemoradiotherapy supported by marrow infusions for advanced neuroblastoma: a Pediatric Oncology Group study.

We conducted a pilot protocol at seven Pediatric Oncology Group (POG) institutions to examine the feasibility, toxicity, and efficacy of using a common regimen of high-dose chemoradiotherapy (HD CT/RT) supported by autologous or allogeneic marrow infusions in children with metastatic neuroblastoma (NBL) in first or second remission. During a 57-month period, we accrued 101 patients. We report here results for the 81 who completed treatment at least 2 years ago. The HD CT/RT regimen consisted of melphalan 60 mg/m2/d for three doses, and total body irradiation (TBI) either 1.5 Gy (n = 27) or 2.0 Gy (n = 54) twice daily for six doses. Twenty-three patients also received irradiation consisting of 1.2 Gy twice daily for 10 doses to persisting disease sites. Seventy-four were given autologous and seven allogeneic marrow, 64 autologous marrows being purged immunomagnetically. Fifty-four children were in first complete (CR) or partial (PR) remission and 27 in second CR or PR. As of October 1, 1990, follow-up was from 32 to 72 months. Forty-seven of these 81 children relapsed, 10 died of complications, one of unknown cause, and 23 continue in remission, including 21 of the 54 treated in first remission, and 16 who completed treatment more than 3 years ago. The 2-year actuarial event-free survival (EFS) probabilities are first CR (CR1) 32% (SE 10%), first PR (PR1) 43% (SE 9%), second CR (CR2) 33% (SE 27%), and second PR (PR2) 5% (SE 5%). Probability of EFS correlated with remission number (first better than second, P less than .001), with interval from diagnosis to HD CT/RT (greater than 9 months better than less than 9 months, P = .055), and with TBI dose (12 Gy better than 9 Gy, P = .031). These encouraging results may partly reflect selection for this treatment of patients with NBL who have a slower disease pace.

Adolescent↗

Allogeneic bone marrow transplantation for patients with high-risk acute lymphoblastic leukemia.

Seventy-four consecutive patients with high-risk acute lymphoblastic leukemia (ALL) were given cyclophosphamide (CY; 50 mg/kg on each of 4 days) plus total body irradiation (TBI; 300 rad on each of 4 days) followed by a human leukocyte antigen (HLA)-identical allogeneic bone marrow transplant (BMT). Eighteen patients in first complete remission (CR1), 36 in CR2, 16 in CR3, and four in CR4 were transplanted. Patients in CR1 were transplanted 1 to 8 months (median, 3 months) after attaining CR. All 18 patients in CR1 had one or more poor risk factors: age more than 18 (N = 17), initial leukocyte count greater than or equal to 20,000 (N = 11), Ph 1 chromosome (N = 2), delay in attaining CR more than 6 weeks (N = 8), or extramedullary disease (N = 1). Of those transplanted in CR2, 72% had relapsed on therapy. The 5-year event-free survival (EFS) rates for patients transplanted in CR1, CR2, and CR3 are 42%, 43%, and 25%, respectively, at median follow-up times of 57, 54, and 72 months, respectively. Children aged less than 18 years transplanted in CR2 have a 5-year EFS rate of 54%. All CR4 patients died early after transplant. The actuarial probability of relapse is 20%, 26%, and 48% for those transplanted in CR1, CR2, and CR3, respectively. Although there was substantial transplant-associated mortality, it decreased over the decade of the study (P = .01). This study indicates that BMT offers an attractive alternative to postremission chemotherapy in patients in CR1 with poor prognostic factors and in patients in second remission.

Adolescent↗

A multicenter trial of antithymocyte globulin in aplastic anemia and related diseases.

One hundred fifty patients with bone marrow failure were treated in three groups with antithymocyte globulin (ATG; Upjohn, Kalamazoo, MI) in a multicenter trial. Patients were assessed at 3, 6, and 12 months after initiation of treatment by three criteria: transfusion independence, clinical improvement, and blood counts. Group I consisted of 77 patients with acute severe aplastic anemia, randomized to receive either ten or 28 days of ATG. There was no significant difference between the two arms of this protocol: 47% of all patients were clinically improved and 31% were transfusion independent at 3 months. Of the severely affected patients, 27% died before 3 months; most deaths occurred early in treatment. Factors associated with survival in severely affected patients included male sex, age less than 40 years, absolute neutrophil count greater than 200/microL, and idiopathic etiology. Neutrophil counts generally increased by 8 weeks after treatment, but patients continued to show improvement to 1 year posttreatment. In Group II, 44 patients with moderate or chronic severe aplastic anemia were randomized to receive either ten days of ATG or 3 months of high-dose nandrolone decanoate. No patient initially treated with androgens recovered, but 28% of ATG-treated cases achieved transfusion independence at 3 months. Group III consisted of patients with a variety of bone marrow failure syndromes. Patients with pancytopenia and cellular bone marrow showed response rates similar to those of patients with chronic or moderate aplastic anemia.

Anemia, Aplastic↗

Intravenous immunoglobulin may lessen all forms of infection in patients receiving allogeneic bone marrow transplantation for acute lymphoblastic leukemia: a pediatric oncology group study.

Fifty patients with refractory acute lymphoblastic leukemia underwent allogeneic bone marrow transplantation after conditioning with high-dose cytosine arabinoside and fractionated total body irradiation. Twenty-nine received intravenous immunoglobulin (i.v.Ig) infusion, primarily to prevent cytomegalovirus infection, and 21 did not. The two groups were biologically comparable. Seven (24.5%) of the i.v.Ig-treated and 14 (66.7%) of the non-i.v.Ig-treated patients developed systemic viral, fungal or bacterial infections and/or interstitial pneumonitis (p less than 0.005), which were fatal in three and 12 cases respectively (p less than 0.001). Currently, 23 (79.3%) of the 29 i.v.Ig-treated and eight (38.1%) of the 21 non-i.v.Ig-treated patients are alive and well (p less than 0.01). We conclude that prophylactic i.v.Ig infusions may reduce the frequency of all forms of serious infection in patients with acute lymphoblastic leukemia undergoing allogeneic marrow transplantation, and thereby improve their survival expectation.

Bone Marrow Transplantation↗

Improved response of patients refractory to random-donor platelet transfusions by intravenous gamma globulin.

Because of frequent unavailability of HLA-compatible platelets or their inefficiency in increasing platelet counts in patients requiring platelet transfusions, platelet refractoriness remains a major problem. Since human gamma globulin has been shown to interfere with the binding of platelet-reactive immunoglobulin G (IgG) to platelets in vitro, and since gamma globulin has proved effective in reversing destruction of platelets in idiopathic thrombocytopenic purpura, we decided to investigate intravenous gamma globulin as an adjunct to random-donor platelet transfusions. We studied three patients, one with acute T-cell leukemia, and two with aplastic anemia. When a total dose of 2 g/kg of body weight of intravenous gamma globulin was infused over five to six days in these patients, two of them showed a remarkable increment in platelet counts and improved hemostasis with random-donor platelet transfusions. We conclude that intravenous gamma globulin may be used in critical situations to improve the response of patients refractory to random-donor platelet transfusions.

Adult↗

Successful engraftment of blood derived normal hemopoietic stem cells in chronic myelogenous leukemia.

The ability of blood-derived stem cells to restore hemopoietic function was investigated in a patient with chronic myelogenous leukemia with bone marrow cells containing the Philadelphia chromosome marker (Ph1+). After treatment with high dose cyclophosphamide, 26.3 X 10(9) blood mononuclear leukocytes, among them 26.2 X 10(5) granulocyte/macrophage progenitor cells (CFUC), were harvested by means of 5 successive leukaphereses when the bone marrow cells had converted to Ph1--. When the patient entered the aggressive phase (blast crisis), myeloablative treatment with busulfan (16 mg/kg) and cyclophosphamide (200 mg/kg) was given, followed by transfusion of the cryopreserved blood leukocytes. Restoration of marrow and blood cellularity was completed about 20 days after this autologous blood stem cell transplantation (ABSCT). Marrow CTUC recovery was complete 2 weeks after ABSCT, and all karyotypes of the patient's marrow cells were free of the marker chromosome. The patient died of toxicity but with normal bone marrow cellularity. This report confirms the therapeutic usefulness of autologous blood-derived stem cells harvested in remission in restoring hemopoietic function after myeloablative treatment.

Adult↗