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Biomedical subjects

E Naparstek

Publications and source records attributed to E Naparstek.

At least 55 records · Page 3Linked to original sources
PubMed1995

Bacterial pneumonia in recipients of bone marrow transplantation. A five-year prospective study.

Bacterial pneumonia as an important complication of bone marrow transplantation (BMT) has not been subjected to comprehensive analysis. Two hundred fifty-five consecutive allogeneic and autologous BMT recipients, ranging in age from 1 month to 53 years, were prospectively followed for 3 days to 3 years (median, 108 days) for development of bacterial pneumonia. Etiology, place acquired, chest radiography, and outcome were recorded and the association between bacterial pneumonia and demographic and clinical variables was analyzed. Thirty-seven (15%) patients experienced 52 episodes of bacterial pneumonia: onset of 13 episodes occurred within 30 days after transplantation, 10 episodes occurred on days +31 to +100, and 29 episodes occurred thereafter. Bacterial pneumonia was the terminal event or contributed to fatal outcome in 8 patients (22% of bacterial pneumonia cases, 3% total study population). Mortality due to hospital-acquired pneumonia (6/21) was significantly higher than (P = 0.03). Bacterial pathogens were identified in 27 (52%) episodes. During the first 100 days after BMT, hospital-acquired Gram-negative bacteria predominated, caused mainly by Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter lwoffi, and Enterobacter cloacae. After day +100, community-acquired, Gram-positive bacteria predominated, particularly Streptococcus pneumoniae. Haemophilus influenzae occurred periodically. Considering all episodes, significant association was found between bacterial pneumonia and veno-occlusive disease (VOD) (P < 0.01) and chronic graft-versus-host disease (GVHD) (P < 0.02). For culture-positive episodes, the association between bacterial pneumonia and VOD was significant (P < 0.001) and borderline for acute GVHD (P = 0.07). It is concluded that VOD and GVHD are positively associated with post-BMT bacterial pneumonia. Its incidence, etiology, risk factors, and outcome are important considerations in its prevention and treatment.

Adolescent↗
PubMed1995

Analysis of beta-globin mutations shows stable mixed chimerism in patients with thalassemia after bone marrow transplantation.

Beta-thalassemia major (TM) is caused by any of approximately 150 mutations within the beta-globin gene. To establish the degree of chimerism after bone marrow transplantation (BMT), we have performed molecular analysis of beta-globin mutations in 14 patients with TM over a period of 10 years. All patients underwent T cell-depleted allogeneic BMT from HLA-identical related donors, using either in vitro T-cell depletion with CAMPATH 1M and complement or in vivo depletion using CAMPATH 1G in the bone marrow collection bag. To date, at different time periods after BMT, seven patients have some degree of chimerism; six of these patients, all blood transfusion-independent, have donor cells in the range of 70% to 95%, with stable mixed chimerism (MC). The seventh patient has less than 10% donor cells with, surprisingly, only minimal transfusion requirements. The detection of beta-globin gene point mutation, as used here, is a highly specific and sensitive marker for engraftment and MC in patients with thalassemia. In light of its specificity, the method is applicable in all cases of TM, as it is independent of sex and other non-globin-related DNA markers. The high incidence of MC found in our patients may be a consequence of the pre-BMT T-cell depletion. Because MC was associated with transfusion independence, complete eradication of residual host cells for effective treatment of TM and possibly other genetic diseases may prove not to be essential.

Alleles↗
PubMed1995

Successful matched unrelated transplantation from a donor with idiopathic thrombocytopenic purpura (ITP).

The case of a 5 year old male is described who had acute myeloblastic leukaemia (AML M5) and was in third remission when he underwent an allogeneic T cell depleted bone marrow transplantation (BMT). The bone marrow was from an HLA matched unrelated donor (MUD) who suffered from chronic idiopathic thrombocytopenic purpura (ITP). In spite of this, the patient had rapid platelet engraftment post BMT (> 50 x 10(9) l-1 on day 20). He is now 12 months post-transplantation and has normal platelet counts, without any clinical or laboratory evidence of ITP. Autoimmune manifestations such as ITP occurring in bone marrow recipients following BMT have been previously reported. Furthermore, severe and protracted thrombocytopenia is a known complication following MUD transplantation and with its respective high risk of graft versus host disease (GVHD). In this case, no signs of ITP could be detected in the recipient despite the fact that the donor had ITP. Our data suggest that in the absence of an alternative choice, a person with ITP should be considered as an appropriate donor for transplantation.

Adult↗
PubMed1995

T-cell-depleted allogeneic bone marrow transplantation for acute leukaemia using Campath-1 antibodies and post-transplant administration of donor's peripheral blood lymphocytes for prevention of relapse.

One hundred and forty-six patients with acute leukaemia (81 with ANLL and 65 with ALL) received allogeneic bone marrow transplantation from their fully matched siblings. 121 patients underwent T-cell depletion (TCD) using Campath 1 monoclonal rat anti-human lymphocyte (CDw52) antibodies; 67 with Campath 1M and 54 with Campath 1G isotypes. Patients were conditioned for transplant using either total body irradiation combined with chemotherapy (125 patients) or busulfan and cyclophosphamide (21 patients). 112 recipients of T-cell depleted allografts received in addition total lymphoid irradiation (TLI) for prevention of rejection. Engraftment of neutrophils (> 0.5 x 10(9)/l) and platelets (> 25 x 10(9)/l) occurred on days 15 and 18, and on days 18 and 20 in recipients of Campath 1M and Campath 1G treated marrows respectively. Rejection was documented in 6.8% of T-cell depleted transplants. Leukaemia relapse-free survival at 2 years was 83% for patients transplanted in first CR, 76% in second CR (P2 = 0.34) and 42% in advanced leukaemia (P2 = 0.009). 81 marrow recipients, 38 with Campath 1M and 43 with Campath 1G treated marrow, received post-transplant graded increments of donor's peripheral blood lymphocytes (PBL) to induce graft-versus-leukaemia (GVL) effects. Administration of donor's PBL was associated with clinically significant GVHD and with decreased relapse rate especially in patients with ALL. Our data suggest that in patients receiving marrow allografts depleted of T cells by Campath 1 monoclonal antibodies, rejection can be reduced by adequate pregrafting immunosuppression. In patients with advanced disease, post-transplant cell-mediated immunotherapy (CMI) using donor's PBL may be beneficial; however, further studies are needed to define the optimal schedule of CMI for safe and effective prevention of relapse following TCD bone marrow transplantation in malignant haematological diseases.

Acute Disease↗
PubMed1995

Modification of M1 cells by exogenous introduction of IL6 gene: a model for gene therapy of acute and chronic myeloid leukemia in mice.

A number of recent studies has shown that animals immunized with cytokine secreting primary tumors show resistance against an unmodified tumor cell challenge. In the present study we have evaluated the potential role of IL6, a myeloid differentiation inducing factor, in modifying myeloid leukemia cells, a tumor so far not challenged by this approach. M1 cells transduced with N2 based retrovirus carrying the murine IL6 gene exhibit morphological and functional alterations. Genetically modified M1 cells show significant reduction in the growth constant coefficient and in the ability to form hematopoietic colonies. Flow cytometry analysis demonstrate increased expression of CD11b, CD18, F4/80, FcR and MHC class II, suggesting driven differentiation towards commitment. Transduced cells secrete high level of autocrine IL6 and, upon activation with LPS, high levels of TNF further indicating a functional alteration and differentiation. The insertion of IL6 gene coding for signals of cell activation and improved expression of MHC antigens into myeloid leukemia cells may enable more effective tumor recognition in vivo, and boost the local as well as the systemic immune-mediated anti-leukemia response.

Acute Disease↗
PubMed1995

Ex vivo expansion of megakaryocyte precursors by preincubation of marrow allografts with interleukin-3 and granulocyte-macrophage colony-stimulating factor in vitro.

Protracted thrombocytopenia and bleeding remain serious complications in bone marrow transplantation (BMT). Major progress has been made in facilitating myeloid and erythroid engraftment, but little has been made in accelerating thrombopoiesis post-BMT. We report that in vitro preincubation of T cell-depleted BM allografts with a combination of interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) (0.1 microgram/mL each) (n = 8), for 3 days prior to infusion, expands megakaryocyte (MK) precursors. MK-progenitor proliferation was assessed in plasma clot colony assays and liquid cultures following pre-exposure to IL-3/GM-CSF. We observed a 2.8-fold increase in the number of colony-forming units-megakaryocyte (CFU-MK) (17.3 +/- 5.2 vs. 6.1 +/- 3.4) (p = 0.001) and a two-fold increase in burst-forming units-megakaryocyte (BFU-MK) (0.2 vs. 0.1) (p = 0.01) per 2 x 10(5) cells/mL compared to control BM samples cultured for 3 days in medium alone. In secondary cultures, the continued presence of IL-3 and GM-CSF increased the number of CFU-MK by 200-fold (p < 0.0001) over controls and by 9.7-fold over fresh BM. A 33-fold increase (p < 0.0001) in the number of BFU-MK was elicited compared to controls. In addition, IL-3 plus GM-CSF supported increased cellularity within the colonies. The presence of IL-3 or GM-CSF alone resulted in fewer MK colonies and fewer cells per colony than both cytokines combined. In liquid cultures, the percentage of cells expressing platelet glycoprotein (GP) IIb/IIIa in the continued presence of IL-3 and GM-CSF increased following preincubation, yielding a total of 16.0 +/- 2.3 x 10(4) MK/2 x 10(6) cells at day 10 of culture. We propose that ex vivo preincubation with IL-3 and GM-CSF can expand the number of MK precursors and may facilitate platelet recovery post-BMT.

Bone Marrow Transplantation↗
PubMed1995

Successful immunization of autologous bone marrow transplantation recipients against hepatitis B virus by active vaccination.

Patients undergoing autologous bone marrow transplantation (BMT) are severely immunosuppressed. These patients are exposed to various infections agents due to delayed and efficient reconstitution of their immune system. Forty-eight patients with hemato-oncological malignancies were immunized against hepatitis B virus (HBV) following autologous BMT. Twenty one were vaccinated more than 10 days before BMT, 17 on days 1-9 before and 10 day after BMT. Thirty three patients (68.7%) seroconverted within 40 days after autologous BMT after receiving one dose of the vaccine before autologous BMT with a relatively low level of anti-HBs, whereas in 11 no anti-HBV antibodies could be detected. Nineteen patients remained seropositive but in 11 the seroconversion was only transient no correlation was found between permanent or transient seroconversion and basic disease, conditioning regimens, post-transplant therapy, immunotherapy and day of vaccination in relation to autologous and day of vaccination in relation to autologous BMT. Active HBV immunization of patients with malignancy undergoing autologous BMT is feasible and levels of antibodies, although low, are above the conventional protective titers. Therefore active immunization of some patients may reduce hepatitis-related complications in the setting of autologous BMT.

Adolescent↗
PubMed1995

Cytosine arabinoside as a major risk factor for Streptococcus viridans septicemia following bone marrow transplantation: a 5-year prospective study.

The incidence and clinical course of nosocomial septicemia with Streptococcus viridans was evaluated prospectively in 242 consecutive bone marrow transplant (BMT) recipients throughout their 15-213 days' (median 47) hospitalization, including 4-58 days (median 18) of neutropenia. Initial empiric therapy for febrile neutropenia consisted of mezlocillin, gentamicin and cefazolin; glycopeptide was excluded. S. viridans septicemia occurred in 23/209 (11%) subjects with underlying malignant disease, and only during neutropenia with concomitant mucositis: in 20 subjects (four with ampicillin-resistant strains), S. viridans septicemia occurred at onset of febrile neutropenia, 1-5 days (median 4.5) post-BMT. All survived with an uncomplicated clinical course. Thus, glycopeptide seems unnecessary in the initial empiric antibiotic regimen. The other three subjects demonstrated S. viridans septicemia (two with ampicillin-resistant strains) on day 11 post-BMT; two died. The major risk identified was cytosine arabinoside administration in the conditioning regimen (P < 0.01).

Adolescent↗
PubMed1995

Allogeneic cell therapy for relapsed leukemia after bone marrow transplantation with donor peripheral blood lymphocytes.

Allogeneic bone marrow transplantation (BMT) is the treatment of choice for hematologic malignancies resistant to conventional chemotherapy and for patients who are at high risk for relapse. Until recently, no cure could be offered to patients relapsing following allogeneic BMT. We present our long-term observations of the first patient with remission reinduced by allogeneic cell therapy (allo-CT) using donor peripheral blood lymphocytes (PBL). In addition, we review the cumulative international experience with allo-CT used to treat 163 patients, 105 with CML and 58 with other hematologic diseases, who relapsed following allogeneic BMT. The first patient treated by allo-CT was diagnosed with acute resistant pre-B lymphoblastic leukemia (ALL) in extensive third hematologic and extramedullary relapse shortly after BMT. He was given infusions of donor (sister) PBL in multiple increments. Subsequently, he developed mild, reversible graft-vs-host disease (GVHD) in parallel with regression of all hematologic and cytogenetic disease manifestations. More than 8 years after allo-CT, he is disease-free with Karnofsky score 100% and no evidence of residual male cells by PCR. International data show that relapse after BMT was successfully reversed by donor PBL treatment in 97 of 158 evaluable patients; 72/100 (72%) with chronic myeloid leukemia (CML) and 25/58 (44.8%) with other malignant hematologic diseases including acute leukemia, lymphoma, and myelodysplastic syndrome. T cell depletion (TCD) for prevention of GVHD was performed for 60/105 (57%) patients with CML and 31/58 (53.4%) patients with other hematologic malignancies. Complete response after allo-CT was obtained in recipients of both TCD-BMT and unmodified BMT. GVHD due to allo-CT developed in 86/158 (54.4%) of the patients, 63/100 (63.0%) with CML and 23/58 (39.6%) with other hematologic diseases. alpha-interferon (IFN-alpha) was given to 67.9% of patients with CML and 28.1% of patients with other diseases. The cumulative experience shows that allo-CT can successfully reverse chemoradiotherapy-resistant relapse of acute leukemia and even more effectively of chronic leukemia independently of alpha-interferon therapy. Although GVHD was frequent among responders, accompanied occasionally by transient or irreversible marrow aplasia, remissions were also obtained in patients with no GVHD. Allo-CT should therefore be considered as treatment of choice for overt relapse or de novo minimal residual disease post-BMT. Administration of donor peripheral blood lymphocytes in graded increments at an early stage of relapse may be the best approach for combining optimal timing at the stage of minimal disease while controlling and minimizing the risk of GVHD on an individual basis.

Adolescent↗
PubMed1994

The anti-emetic efficacy and tolerability of tropisetron in patients conditioned with high-dose chemotherapy (with and without total body irradiation) prior to bone marrow transplantation.

Nausea and vomiting are among the most distressing side-effects of chemoradiotherapy. Conditioning protocols for patients undergoing bone marrow transplantation consist of highly emetogenic high-dose chemotherapy with or without total body irradiation. Marked improvement in controlling emesis and nausea was achieved by the introduction of a new class of antiemetic drugs, the 5HT3 serotonin-receptor antagonists. Tropisetron is a highly potent, selective antagonist of 5HT3 receptors. Previous studies have used a single 5-mg dose i.v. of tropisetron to control nausea and vomiting in cancer patients. The present study was undertaken to evaluate the efficacy and safety of a single daily dose of tropisetron in controlling emesis in patients receiving high-dose chemotherapy (with or without total body irradiation) prior to bone marrow transplantation. The anti-emetic efficacy was investigated in a non-homogeneous cohort in a prospective and open study. Of 11 patients evaluated, 9 (81%) showed complete or major control, 1 (9%) minor control and 1 (9%) failed to respond. The most common adverse events reported during the study included diarrhea (46%) and headache (18%), no patients being withdrawn because of side-effects. Our data suggest that a single 5-mg i.v. dose of tropisetron is safe and effective in preventing chemotherapy-induced emesis in patients receiving bone marrow transplantation conditioning. A larger randomized study is warranted to confirm our preliminary results.

Adolescent↗
PubMed1994

Intracranial haematomas following bone marrow transplantation.

Intracranial haemorrhage (ICH) is a known grave complication of leukaemia and has been described post mortem following bone marrow transplantation (BMT). Ante mortem following BMT, the incidence and significance of ICH is not well defined. The records of 471 bone marrow transplantation recipients over 11 years at the Hadassah University Hospital Bone Marrow Transplantation Department were reviewed. The relevant data of all patients with ICH were analysed. A resolute diagnostic and treatment protocol for subdural haematomas had been employed. The indication for transplantation in 273 of the patients was leukaemia. Thirteen of these patients developed subdural haematomas within 42 days of the transplant, and nine of these haematomas were bilateral. None of the 198 patients with other malignancies or nonmalignant indications for BMT (predominantly aplastic anaemia and beta thalassaemia major) had subdural haematomas. One thalassaemia patient and three leukaemia patients had intracerebral haematomas. There was no mortality or major morbidity from the subdural haematomas, which were all successfully resolved. In contrast, all of the patients with intracerebral haematomas consequently died. Subdural haematomas occur in approximately 5% of patients with leukaemia following BMT, but the clinical outcome is relatively benign. Intracerebral haematomas are a sporadic, lethal complication following BMT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Combined therapy of granulocyte transfusions, intravenous opsonins and antibiotics for gram-negative pneumonia in neutropenic cancer patients.

Four patients with hematological malignancies, following bone marrow transplantation, who developed documented gram-negative [Klebsiella pneumoniae (2), Pseudomonas aeruginosa or Acinetobacter calcoaceticus] pneumonia during absolute neutropenia, were treated with a combination of antimicrobial therapy, granulocyte transfusions, and high-dose intravenous immunoglobulin. The patients recovered following this regimen, including 2 who had septic shock and respiratory failure, necessitating intubation and mechanical ventilation. These data suggest that therapy combining antimicrobial agents, granulocyte transfusions and opsonins may be effective in neutropenic patients who develop gram-negative pneumonia.

Adult↗
PubMed1994

Total lymphoid irradiation, anti-lymphocyte globulin and Campath 1-G for immunosuppression prior to bone marrow transplantation for aplastic anemia after repeated graft rejection.

Allogeneic BMT for severe aplastic anemia is associated with a significant rate of graft rejection, especially in patients who have been previously transfused. We report a child with aplastic anemia who rejected donor marrow twice despite adequate immunosuppression as part of the conditioning therapy but engrafted successfully following combined administration of three modalities of immunosuppression: antithymocyte globulin, total lymphoid irradiation and the monoclonal antibody Campath-1G. Restriction fragment length polymorphism studies > 1 year after BMT show full donor hematopoiesis with no evidence of autologous recovery.

Alemtuzumab↗
PubMed1993

Normal hematopoietic reconstitution following ASTA-Z 7557-purged grafts in the absence of in vitro CFU-GM colony growth.

Hematopoietic reconstitution was assessed in 26 consecutive patients who underwent autologous bone marrow transplantation (ABMT) with ASTA-Z 7557 purged bone marrows. Of the 26, 17 had acute non-lymphoblastic leukemia (ANLL), 7 had acute lymphoblastic leukemia (ALL), 1 had non-Hodgkin's lymphoma (NHL) and 1 had multiple myeloma (MM). Twelve patients had practically no CFU-GM growth after ASTA-Z treatment. No statistical difference was observed in hematopoietic reconstitution between patients with or without in vitro CFU-GM colony growth. No significant linear correlation was observed between CFU-GM content in the treated graft and day of engraftment. In vitro CFU-GM growth has no predictive value in assessing hematopoietic recovery in vivo. Patients with no CFU-GM growth demonstrated normal engraftment.

Adolescent↗