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Biomedical subjects

E Naparstek

Publications and source records attributed to E Naparstek.

At least 91 records · Page 5Linked to original sources
PubMed1991

Acute inflammatory demyelinating polyneuropathy following bone marrow transplantation.

Acute inflammatory demyelinating polyneuropathy (AIDP) appeared in two patients following allogeneic bone marrow transplantation (BMT). In one transplanted patient (but not in the donor) T cells were sensitized against peripheral nervous system myelin. This could reflect a change in the T cell repertoire in a different milieu. In this context, AIDP might be part of graft-versus-host disease or another associated autoimmune disorder following BMT.

Adolescent↗
PubMed1991

Transient elevation of serum lactic dehydrogenase following autologous bone marrow transplantation.

Transient elevated levels of serum lactic dehydrogenase (LDH) were reported immediately following autologous bone marrow transplantation consecutively in 15 patients. Isoenzyme 2 was the predominant elevated isoenzyme of LDH, suggesting that the source of LDH is either hemolysis of RBCs, which occurs during freezing and thawing of bone marrow in the bags and in vivo following infusion of residual dimethyl sulfoxide.

Adolescent↗
PubMed1990

Interstitial pneumonitis after total body irradiation: effect of partial lung shielding.

The potential beneficial effects of partial lung shielding were investigated in 44 patients conditioned by whole body radiotherapy as part of the conditioning for bone marrow transplantation (BMT). The first 23 patients were irradiated with fractionated total body irradiation (TBI) to a total dose of 12 Gy. In the second series of 21 patients a 50% transmission lung shield was utilized following 6 Gy TBI. This treatment was combined in the second group with four fractions of 1.5 Gy total lymphoid irradiation (TLI), given in 2 d. The rate of idiopathic interstitial pneumonitis (IP) was 26% in the first group, compared to none in the second.

Adolescent↗
PubMed1990

The use of recombinant cytokines for enhancing immunohematopoietic reconstitution following bone marrow transplantation. II. The influence of lymphokines on CFU-GM colonies from human untreated, ASTA-Z or Campath-1M treated bone marrow.

Patients undergoing bone marrow transplantation (BMT) are subjected to the risk of pancytopenia in the immediate post-BMT period. Recipients of bone marrow (BM) autografts purged in vitro by chemical agents such as mafosfamide (ASTA-Z) are even more likely to develop a delayed engraftment. In a previous study in mice, we showed earlier immunohematopoietic reconstitution after syngeneic marrow grafting with BM cells precultured with single or combined cytokines. In this work we determined optimal culture conditions for the use of single and various cytokine combinations in order to activate progenitor cells following in vitro cultures of untreated, ASTA-Z purged or T cell-depleted human BM preparations prior to BMT. The best single cytokine for enhancing CFU-GM was found to be GM-CSF (0.1 mg/ml) which produced an increase of up to 8-fold over controls after 3 days' incubation. Addition of recombinant human interleukin 3 (rhIL3) (0.1 mg/ml) to rhGM-CSF had an additive effect. The same enhancing effect of in vitro CFU-GM by both cytokines was observed following ASTA-Z purging of BM cells obtained from patients undergoing autologous BMT. Similarly, depletion of lymphocytes from BM using the monoclonal rat anti-human lymphocyte antibody Campath-1M and human complement did not diminish the beneficial influence of rhIL3 and rhGM-CSF. When combined with rhGM-CSF and rhIL3, rhIL1 and rhIL2 had no appreciable enhancing effect on CFU-GM and occasionally even reduced it. We suggest that enhancement of differentiation of hematopoietic progenitor cells may be accomplished by in vitro incubation of BM cells without continuous administration of cytokines in vivo following BMT.

Antineoplastic Agents↗
PubMed1990

The graft-versus-leukemia (GVL) phenomenon: is GVL separable from GVHD?

Graft-versus-leukemia (GVL) is a major component of the overall beneficial effects of allogeneic bone marrow transplantation (BMT) in the treatment of leukemia. Although several clinical trials have suggested a direct relationship between GVL effects and acute and chronic graft-versus-host disease (GVHD), it is not yet known whether GVL can be separated from GVHD. However, several investigations in murine models of human leukemia indicate that the two may be at least partially separable. Moreover, analysis of clinical data from the International Bone Marrow Transplant Registry suggest that allogeneic BMT may be more advantageous than syngeneic BMT, regardless of the GVHD. Likewise, T lymphocyte depletion is associated with an increased incidence of relapse, independently of GVHD. Recent investigations in murine leukemia suggest that GVL-like effects may be inducible following syngeneic BMT by recombinant cytokines with no overt GVHD. Taken together, current data in experimental animals and man suggest that GVL may be at least partially separable from GVHD. Hence, further understanding of effector and target cells of GVL as well as our ability to induce antitumor effector cells, especially those that are MHC nonrestricted, may lead to new approaches for potentiating anti-tumor effector mechanisms without inducing severe, clinically overt GVHD. Successful attempts in these directions may also lead to improved results following autologous BMT as a result of activation of GVL-like effects by recombinant cytokines that are capable of activating effector cells with anti-leukemic activity in vivo, such as recombinant human IL2, alpha interferon or perhaps a synergistic combination of factors.

Animals↗
PubMed1990

Immunotherapy in conjunction with autologous bone marrow transplantation.

Although high-dose chemoradiotherapy used for conditioning prior to autologous bone marrow transplantation (BMT) represent an effective tool for eradication of certain malignant hematological disorders, relapses indicate that the last tumor cell is unlikely to be completely eradicated. We are investigating several approaches for controlling residual tumor cells escaping from chemoradiotherapy by cellular adoptive immunotherapy and amplification of natural defense mechanisms, using recombinant human IL2 (Cetus, Emeryville CA), in a murine model of leukemia/lymphoma disease (BCL1).

Animals↗
PubMed1989

Osteogenic response to marrow aspiration: increased serum osteocalcin and alkaline phosphatase in human bone marrow donors.

It has been shown recently in experimental animals that regeneration of bone marrow after ablation is associated with enhanced osteogenic growth factor activity and a systemic increase in bone formation. To assess the possible occurrence of a similar phenomenon in humans, serum markers of bone formation, osteocalcin and alkaline phosphatase, were measured in marrow donors before the aspiration of large amounts of iliac marrow and 1 day to 5 weeks thereafter. Both osteocalcin and alkaline phosphatase showed significant increases, with peak values 1-3 and 2-4 weeks postaspiration, respectively. The absolute maximal increase in osteocalcin was significantly higher in adolescent and child donors than in adults. When evaluated together with studies on systemic changes during fracture healing and marrow regeneration, these findings suggest that marrow aspiration in humans evokes a systemic osteogenic response.

Adolescent↗
PubMed1989

Severe giardiasis in two patients undergoing bone marrow transplantation.

Two patients undergoing bone marrow transplantation developed severe gastrointestinal symptoms, one during the peri-transplantation period and the other several months post-transplantation and following documented intestinal graft-versus-host disease. After detection of Giardia lamblia trophozoites in a stool specimen from one patient and a duodenal aspirate from the other, treatment with metronidazole was administered and all symptoms resolved. Giardiasis should be considered in transplant patients with diarrhea. Negative stool examinations do not rule out this possibility, and consideration should be given to examining a sample of small intestinal contents for Giardia trophozoites.

Adult↗
PubMed1988

T-cell depleted bone marrow transplantation for plasma cell myeloma. Report of a case and review of the results of BMT for myeloma.

A 37-year-old male patient with advanced refractory plasma cell myeloma underwent T-cell depleted bone marrow transplantation (BMT) after 7 years of active disease previously treated with combination chemotherapy and irradiation. After the BMT there was marked clinical improvement and the patient is currently in good clinical condition two years after the BMT was performed. However, residual myeloma cells are still seen in the marrow and stable levels of paraprotein are still present in the serum. No GVHD was encountered after BMT. The problems of BMT in myeloma are discussed with a review of the current pertinent literature.

Adult↗
PubMed1988

Bone marrow transplantation in beta-thalassemia major. The Israeli experience.

The present report summarizes our experience in applying a new approach in bone marrow transplantation for the treatment of beta-thalassemia major. Ex-vivo pretransplant T-lymphocyte depletion with CAMPATH-1 was used for prevention of acute and chronic graft versus host disease and total lymphoid irradiation was added for the conditioning regimen for abrogation of potential rejection of T-cell depleted marrow allografts. Ten patients with homozygous beta-thalassemia major were 9-48 months of age (median 18.5 months) and received HLA-identical allogeneic T-cell depleted marrow after treatment with total lymphoid irradiation, busulfan and cyclophosphamide. Seven patients are alive and free of disease, 3-46 months post-transplantation. The actuarial probability of survival and of disease-free survival at two years was 70%. Three patients died: one of intracranial hemorrhage post-transplantation, one from busulfan interstitial pneumonitis, and one who rejected the first graft and developed fatal chronic graft versus host disease after a second transplant. Seven patients are alive and well with follow-up of 3-45 months, with no signs of acute or chronic GVHD. We conclude that T-cell depleted bone marrow transplantation is indicated for homozygous transfusion dependent young patients with beta-thalassemia who are minimally transfused, particularly in areas where optimal conventional therapy is not feasible.

Bone Marrow Transplantation↗
PubMed1988

Treatment with itraconazole of widespread tinea corporis due to Trichophyton rubrum in a bone marrow transplant recipient.

An immunocompromised patient, 6 weeks after bone marrow transplantation, developed extensive skin infection due to Trichophyton rubrum. Because she could not tolerate ketoconazole and was hypersensitive to griseofulvin, she received itraconazole with complete recovery within 30 days. This case demonstrates that itraconazole may be effective treatment for dermatophytosis, even in immunocompromised hosts, and that there is no cross-reactivity between ketoconazole and itraconazole.

Adult↗
PubMed1988

Interstitial pneumonitis in T cell-depleted bone marrow transplantation.

The incidence of interstitial pneumonitis (IP) was reviewed in 80 consecutive patients who received allogeneic T lymphocyte-depleted bone marrow transplantation (BMT) for malignant and non-malignant diseases. Pretransplant conditioning used in malignant disorders included total lymphoid irradiation (TLI) 150 cGy x 4, total body irradiation (TBI) 200 cGy x 6, and cyclophosphamide (CY) 120 mg/kg. In non-malignant diseases conditioning included no TBI, but adjusted doses of TLI in addition to CY (severe aplastic anemia) or CY and busulfan (severe beta-thalassemia major). In the malignant group only one patient developed graft-versus-host disease (GVHD) grade I; IP developed in 12 out of 61 patients (19.7%) and IP-associated fatality occurred in five patients (8.2%). Cytomegalovirus (CMV) was associated with only two of the five fatal IP. In the non-malignant group there was no GVHD; one patient out of 19 (5.2%) had IP, which was fatal and not associated with CMV. These data indicate that fatal IP may appear in the absence of GVHD. The relatively low incidence of IP-related mortality in recipients of allogeneic T lymphocyte-depleted BMT suggests that although prevention of GVHD and elimination of drugs used for GVHD prevention may reduce the incidence of fatal pulmonary complications, other approaches have to be investigated for complete prevention of IP which still represents a major complication in patients with malignant hematologic disorders treated by allogeneic BMT.

Adult↗
PubMed1988

Preliminary characterization of functional residual host-type T lymphocytes following conditioning for allogeneic HLA-matched bone marrow transplantation (BMT).

Host T lymphocytes which escape the effects of chemoradiotherapy may proliferate and lead to graft rejection, particularly in recipients of T cell-depleted bone marrow (BM) allografts. We studied the efficacy of several conditioning regimens including a new immunosuppressive regimen--total lymphoid irradiation (TLI) plus conventional chemotherapy and total body irradiation (TBI)--in abrogating residual host T lymphocytes as assessed by their ability to grow in vitro. A total of 38 patients were evaluated, 29 with hematologic malignancies, six with severe aplastic anemia (AA) and three with beta-thalassemia major (TM), of whom 32 were transplanted with HLA-identical T cell-depleted allogeneic BM from sibling donors. The median observation period was 15 months (range 3-21) posttransplant. Peripheral blood mononuclear cells (PBMC) taken from each patient on the day of transplant were cultured with interleukin 2 (IL-2) + phytohemagglutinin + irradiated donors' PBMC. Survival of cells for less than 2 weeks in vitro without proliferation was observed in 20 of 29 cases with malignancies and was considered negative. In this group only two leukemia (L) patients rejected the graft. Limited cell growth (less than or equal to 3 weeks) was seen in four L patients, two of whom showed early graft failure. Vigorous T cell growth (greater than 5 weeks, 62-96% CD4+ cells) was noted in eight cases (two L, four AA, two TM; none received TBI). In this group, sustained engraftment was observed in 7/7 patients who were treated with cyclosporin A (CSA) post grafting. Overall, we could demonstrate no clear correlation between graft failure and cell growth in vitro. The proliferating cells exhibited considerable cytotoxic activity in vitro against several tumor cell lines and were susceptible to pharmacological doses of CSA. The low incidence of continuous T cell proliferation in vitro in PBMC of L patients suggests that a combination of TLI, TBI and cyclophosphamide (CY) is highly effective in abrogating the host T cells and subsequent graft rejection. Since a rather small number of patients was included in this study, further studies are needed to determine the possible value of the in vitro T cell proliferation assay as a means for predicting graft failure.

Adolescent↗