Biomedical subjects

J Kapelushnik

Publications and source records attributed to J Kapelushnik.

At least 37 records · Page 2Linked to original sources

PubMed1999

Donor lymphocyte infusion post-non-myeloablative allogeneic peripheral blood stem cell transplantation for chronic granulomatous disease.

Chronic granulomatous disease (CGD) is a primary immunodeficiency disease symptomized by failure to generate superoxide and recurrent bacterial and fungal infections. Allogeneic bone marrow transplantation (BMT) is one of the therapeutic options available. However, it presents considerable risk to the recipient, especially if the patient is already at an advanced stage of disease, after repeated bacterial and fungal infections and organ damage. We present a case report of a 6-year-old child with long-standing CGD, severe clubbing, and jeopardized pulmonary function after multiple bacterial pulmonary infectious episodes, who had failed treatment with sulphamethazole trimethoprim, multiple antibiotic courses, itraconazole, as well as steroid and interferon-y therapy. He underwent allogeneic peripheral blood stem cell transplantation (alloPBSCT) from his HLA-matched MLC non-reactive sister following non-myeloablative conditioning. His ANC did not fall below 0.2 x 10(9)/l, his lowest WBC was 0.6 x 10(9)/l, and his platelets did not fall below 28 x 10(9)/l. He had normal engraftment, with no mucositis or organ toxicity. Neither parenteral nutrition nor platelet infusions were necessary. Partial donor chimerism following alloPBSCT was converted to full donor chimerism and superoxide production reverted to normal after donor lymphocyte infusions (DLI) from his HLA-matched sister. Twenty four months post transplant the patient is well, with stable and durable engraftment, 100% donor chimerism, normal superoxide production, no GVHD, and stabilization of his pulmonary condition. We suggest that alloPBSCT preceded by non-myeloablative conditioning and followed by DLI may constitute a successful mode of therapy for patients suffering from advanced CGD with recurrent infectious episodes resulting in organ dysfunction, enabling them to achieve full donor chimerism and normal superoxide production with minimal risk of transplant-related toxicity and GVHD.

Child↗

PubMed1999

Graft-versus-lymphoma effect after allogeneic peripheral blood stem cell transplantation for primary central nervous system lymphoma.

Allogeneic peripheral blood stem cell transplantation (allo PBSCT) is a recognized treatment modality for hematological malignancies resistant to conventional chemoradiotherapy. The post-transplant immune-mediated graft-versus-leukemia effect has major curative potential. In this case presentation, the allogeneic approach to resistant recurrent primary central nervous system (CNS) lymphoma using peripheral blood stem cells from an HLA identical sibling after immuno-suppressive non-myeloablative conditioning, was examined clinically. The patient in question had relapsing refractory primary CNS lymphoma and is the first to be treated with this modality. She developed early skin and liver-localized grade II graft-versus-host disease after allo PBSCT, which then responded to short-term treatment. Chimeric studies at the time showed 100% donor cells and repeated magnetic resonance imaging of the brain revealed gradual shrinkage of the tumor. Three months after transplant the cerebral mass was no longer evident and currently, 30 months after transplantation, the patient continues to be disease free. The absence of any signs of malignancy suggests the development of a durable graft-versus-lymphoma effect in this brain tumor and indicates that this effect may be achieved even after non-myeloablative conditioning.

Adult↗

PubMed1998

Bone marrow transplantation from a cadaveric donor.

A 2.5-year-old girl with neurogenic Gaucher's disease was transplanted with donor bone marrow from her HLA-compatible 12-year-old brother whose marrow was harvested 30 min post-mortem, after he suffered a severe head and neck injury. The marrow was stored in liquid nitrogen for 30 days prior to infusion. The post-transplantation period was uneventful with good engraftment and no signs of graft-versus-host disease. Currently, 6 months post-allogeneic bone marrow transplantation (alloBMT), analysis of both bone marrow and blood samples by PCR documented only cells of donor origin. This case demonstrates the feasibility of cadaveric marrow as a source of donor cells. To our knowledge, this patient is the only survivor of alloBMT from a cadaveric donor.

Bone Marrow Transplantation↗

PubMed1998

Chronic graft-versus-host disease treated with UVB phototherapy.

Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic bone marrow transplantation. Immunosuppressive treatment regimens carry the potential of causing severe morbidity and mortality, so that additional modes of therapy with fewer side-effects are clearly needed. Five cGVHD patients (sclerodermoid cGVHD in two patients, lichenoid cGVHD in one patient and intraoral cGVHD in two patients), who had not responded to standard immunosuppressive drugs, were treated with adjuvant UVB phototherapy. The patient with lichenoid cGVHD experienced complete clearing of cutaneous lesions, whereas both patients with sclerodermoid cGVHD experienced significant relief of pruritus, but showed no change of the sclerodermoid skin lesions. Intraoral lesions cleared in one patient. The effects of UVB phototherapy were furthermore documented by measurement of skin viscoelasticity and mouth opening. No side-effects were encountered. This preliminary study suggests that UVB phototherapy is useful as an adjuvant therapeutic modality in intraoral and cutaneous lichenoid cGVHD.

Adolescent↗

PubMed1998

Allogeneic cell-mediated and cytokine-activated immunotherapy for malignant lymphoma at the stage of minimal residual disease after autologous stem cell transplantation.

Immunocompetent donor-derived T lymphocytes play a crucial role in the elimination of residual leukemic cells post allogeneic bone marrow transplantation. Because this graft versus leukemia (GVL) effects is absent after autologous stem cell transplantation (ASCT), a high rate of relapse ensues. We introduced cell-mediated immunotherapy at the stage of minimal residual disease in lymphoma patients to help effect a GVL-like reaction by adoptive transfer of immunocompetent human leukocyte antigen-matched donor peripheral blood lymphocytes (PBL). Thirteen consecutive patients with high-risk lymphoma were treated with allogeneic cell therapy (AlloCT) after having undergone ASCT. In the absence of graft-versus-host disease, cell therapy-induced graft-versus-lymphoma reaction was amplified by human recombinant interleukin 2 (rIL-2) during 3 days to activate donor PBL in vivo, followed by infusion of in vitro rIL-2 activated donor lymphocytes combined with 3-day rIL-2 therapy. Nine of the patients underwent the treatment protocol well. In the four other patients, in whom the AlloCT resulted in marrow aplasia due to elimination of host hematopoietic cells, treatment with donor marrow cell infusion without further conditioning was performed. Adoptive cell therapy in the form of AlloCT may turn out to be an effective therapeutic modality for the treatment of resistant residual disease in lymphoma patients.

Adolescent↗

PubMed1998

Use of fiberoptic bronchoscopy in bone marrow transplant recipients.

Bone marrow transplantation (BMT) has become the therapy of choice for a number of malignant and nonmalignant hematologic and nonhematologic disorders. A frequent complication after BMT is pulmonary disease which is associated with a high mortality rate. We examined the results of 79 bronchoscopies performed between May 1991 and May 1995 in 62 patients for the evaluation of pulmonary complications after BMT. In all cases bronchoalveolar lavage (BAL) was performed, in 10% transbronchial biopsy (TBB) was also carried out and in 13% bronchoscopy was followed by open lung biopsy. Positive results were found in 67% of bronchoscopies. Fungal infection (Candida and Aspergillus species) was the most common finding (18%), bacterial infection was found in 13%, mixed (fungal and bacterial) infection in 6%, cytomegalovirus in 11% and Pneumocystis carinii pneumonia in 4%. Diffuse alveolar hemorrhage was detected in 11% of cases. Idiopathic pneumonia syndrome (IPS) was diagnosed by TBB in 3% of procedures. We conclude that BAL is a safe and accurate procedure for the evaluation of pulmonary complications after BMT. TBB should be considered in the absence of thrombocytopenia for the diagnosis of IPS. If bronchoscopy findings are negative, open lung biopsy should be considered.

Adolescent↗

PubMed1998

Allogeneic cell-mediated immunotherapy for breast cancer after autologous stem cell transplantation: a clinical pilot study.

Allogeneic cell therapy (allo-CT) is emerging as an effective treatment for patients relapsing after allogeneic bone marrow transplantation (BMT), indicating that tumor cells resisting chemoradiotherapy may still respond to immunocompetent allogeneic lymphocytes. We investigated possible graft-versus-tumor (GVT) effects in six patients with metastatic breast cancer that would be comparable to the graft-versus-leukemia (GVL) phenomenon occurring after allogeneic BMT in hematologic malignancies. The patients were cytoreduced with high-dose chemotherapy and autologous stem cell transplantation (ASCT), and were treated ambulatory with allo-CT consisting of adoptive transfer of HLA-matched donor peripheral blood lymphocytes (PBL) activated in vivo with human recombinant interleukin-2 (rIL-2). If no graft-versus-host disease (GVHD) developed, allo-CT was augmented with infusion of donor PBL, preactivated in vitro with rIL-2. Treatment was well tolerated, with low therapy-related toxicity in all patients. Two patients developed signs and symptoms compatible with GVHD grade I-II, one of whom shows no evidence of disease at more than 34 months out. In the remaining patients, progression-free survival following allo-CT ranged between 7 and 13 months. Allogeneic cell-mediated, cytokine-activated immunotherapy might be utilized for induction of GVT in metastatic breast cancer. A search for techniques to boost chimerism without severe GVHD is indicated.

Adult↗

PubMed1997

A fludarabine-based protocol for bone marrow transplantation in Fanconi's anemia.

Allogeneic bone marrow transplantation (BMT) is an effective therapy for Fanconi's anemia (FA). However, mortality and transplant-related complications are usually high due to increased sensitivity to the alkylating agents and radiation commonly used for pre-transplant conditioning. Fludarabine monophosphate is a purine analogue that has been proven effective as a conditioning agent for chronic lymphocytic leukemia patients. We report a child with FA in leukemic transformation with thrombocytopenia and 20% myeloblasts who underwent successful BMT following conditioning with fludarabine/ATG/cyclophosphamide. The regimen was well tolerated, no transplant-related complications were observed, and engraftment was rapid. The child is currently 10 months post-BMT, in excellent clinical condition with a normal blood count, 100% chimerism and no sign of graft-versus-host disease (GVHD). We suggest that this fludarabine-based regimen may be effective in the conditioning of standard, as well as transforming, FA patients for BMT.

Antineoplastic Agents↗

PubMed1997

Should soybean agglutinin purging be performed in breast cancer patients undergoing autologous stem cell transplantation? A retrospective analysis of 48 patients.

High-dose chemotherapy (HDC) followed by autologous stem cell transplantation (ASCT) has gained an increasing role in the treatment of high-risk Stage II-III and/or metastatic breast cancer patients. Several investigators reported on a high rate of tumor cells contaminating the bone marrow and peripheral blood stem cell collection. Nevertheless, the clinical implication of reinfusion of tumor cells with the stem cells to the relapse rate is still uncertain. In this retrospective analysis we compare the outcome and the toxicity of 29 patients with high-risk Stage II-III and 19 metastatic breast cancer patients who underwent HDC with ASCT. Thirteen patients underwent transplant with soybean agglutinin (SBA)-purged graft, while 35 consecutive patients received unmanipulated graft. Engraftment was significantly faster for the nonpurged transplant. No differences in disease-free survival, freedom from relapse, or overall survival were noted in both groups during a median follow up time of 14 months. We conclude that tumor cell purging using SBA in breast cancer patients is not warranted. New purging methods are needed to assess the role of tumor cell purging in breast cancer patients.

Adult↗

PubMed1996

Low molecular weight heparin for the prevention of veno-occlusive disease of the liver in bone marrow transplantation patients.

Hepatic veno-occlusive disease (VOD), a common complication of bone marrow transplantation (BMT), is a result of intensive conditioning by chemo-radiotherapy. Endometrial injury causes fibrin deposition in the affected hepatic venules, leading to abnormal laboratory parameters followed by lethal full-blown disease. Previous studies have shown that unfractionated heparin can prevent VOD in BMT patients. Since low molecular weight heparin (LMWH) preserves the antithrombotic, but not the anticoagulant, activity of unfractionated heparin, we initiated a pilot study to determine the safety of LMWH for the prevention of VOD. Sixty-one patients undergoing BMT (allogeneic, n=24; autologous, n=37) were randomized to receive subcutaneous injection of enoxaparin (40 mg/day x 1) or a placebo prior to BMT conditioning and until day 40 after transplantation or discharge from the hospital. LMWH administration did not influence marrow engraftment, nor was it associated with bleeding tendency. Hemorrhagic events occurred significantly less frequently (P=0.025) were shorter duration (P=0.006) in the LMWH group than in the placebo group. Time to platelet recovery was significantly shorter (16.5 vs 29.6 days, (P=0.0075), and platelet transfusion requirements were lower (p=0.05) in the LMWH patients. VOD parameters occurred less frequently in the experimental group, including duration of elevated bilirubin levels (P=0.01) and incidence of hepatomegaly (P=0.04). LMWH, which seems to enhance platelet recovery, may be safely administrated to BMT patients in an attempt to prevent VOD of the liver.

Adult↗

PubMed1996

Allogeneic cell therapy with donor peripheral blood cells and recombinant human interleukin-2 to treat leukemia relapse after allogeneic bone marrow transplantation.

Allogeneic bone marrow transplantation (BMT) is the only effective treatment for hematologic malignancies resistant to conventional chemotherapy. Until recently, no cure existed for patients who relapsed post-BMT. We present our long-term observations on remission induction, after relapse post-BMT, by allogeneic cell therapy (allo-CT) and the feasibility of remission induction in allo-CT-resistant patients by activation of antileukemia effector cells with recombinant human interleukin-2 (rhIL-2) in vitro and in vivo. The longest observation of successful allo-CT (event-free survival, greater than 8 years) was made in a patient with resistant pre-B lymphoblastic leukemia who received infusions with graded increments of donor (female) peripheral blood lymphocytes (PBL) as soon as bulky hematologic and extramedullary relapse was noticed early post-BMT. The patient is currently without evidence of residual host (male) cells as determined by polymerase chain reaction (PCR). Of 17 patients with acute and chronic leukemia in relapse after BMT, 10 were reinduced into complete remission. Four patients with cytogenetic relapse responded to allo-CT alone, while five of six patients with overt hematologic relapse responded only after additional activation of donor with rhIL-2. Allo-CT can, therefore, successfully reverse chemoradiotherapy-resistant relapse of both acute and chronic leukemia. Moreover, in patients resistant to donor lymphocyte infusion, remission can be accomplished by additionally activating donor PBL in vitro and/or in vivo with rhIL-2. Based on our observations, after BMT, allo-CT should be considered the treatment of choice for patients with hematologic malignancies resistant to conventional anticancer modalities. Allogeneic activated cell therapy (allo ACT) should be considered for patients with tumor cells resistant to allo-CT. Although allo-CT, followed if indicated by allo-ACT, can be effective for patients with overt hematologic relapse, reversal of persistent minimal residual disease or documented molecular/cytogenetic relapse early after BMT may also be considered as a possible indication for allo-CT.

Adolescent↗

PubMed1996

Normalization of serum lactic dehydrogenase in beta-thalassemia patients following bone marrow transplantation.

Serum lactic dehydrogenase (LDH) levels are mildly elevated in beta-thalassemia major due to ineffective erythropoiesis. We reviewed the charts of 15 consecutive thalassemic children who underwent allogeneic, T-cell-depleted bone marrow transplantation (BMT) in our department during the last 3 years. Eleven patients had successful engraftment and are alive and well without evidence of disease, according to physical examinations, blood counts, and polymerase chain reaction (PCR) tests, with a median follow-up of 2 years. Two patients died due to transplantation-related complications, and two rejected the graft and received their backup autologous marrow. The LDH levels in the transplanted patients gradually decreased from an average of 952 +/- 155 IU/L 10 days pre-transplant (N = 300-620) to 426 +/- 56 IU/L at the day of transplantation, and stayed at approximately the same level post-transplant (489 +/- 55 IU/L). By contrast, the LDH levels reverted to the pre-transplant value in those patients who rejected their marrow. The significance of this clinical observation for the pathophysiologic mechanism of intramedullary hemolysis and ineffective erythropoiesis in beta-thalassemia major is discussed.

Bone Marrow Transplantation↗

PubMed1996

Second transplantation using allogeneic peripheral blood stem cells in a beta-thalassaemia major patient featuring stable mixed chimaerism.

Allogeneic bone marrow transplantation (BMT) for beta-thalassaemia major carries the risks of disease recurrence due to residual thalassaemic stem cells or true immune-mediated rejection. We report a thalassaemic patient who displayed stable mixed chimaerism with only 5% donor-derived cells for about 5 years after BMT. Displacement of host cells was accomplished by ambulatory non-myeloablative conditioning and allogeneic G-CSF mobilized peripheral blood stem cell transplantation from the same donor, resulting in full reconstitution. Patients featuring stable mixed chimaerism after BMT may benefit from allogeneic cell therapy with immunocompetent lymphocytes and stem cells, whilst avoiding supralethal conditioning.

Bone Marrow Transplantation↗

PubMed1996

Teething and acute graft vs. host disease: a clinical observation.

A 5-month-old girl, treated with bone marrow transplantation for severe combined immunodeficiency, developed two episodes of severe acute graft vs. host disease (GVHD) while teething. A dramatic improvement in GVHD was noted after the completion of tooth eruption. It is suggested that the release of interleukin-1, associated with the traumatized gingival tissue, is the triggering mediator for the GVHD.

Acute Disease↗

PubMed1996

Hydronephrosis in children after bone marrow transplantation: case reports.

Hydronephrosis post-bone marrow transplantation (BMT) diagnosed in five children, was caused by hemorrhagic cystitis and blood clots in the bladder, congenital uretro-pelvic junction stenosis and ureteral obstruction due to adenoviral infection. Patients received conservative therapy to treat the symptoms. However, hydronephrosis did not change the outcome of BMT. Therefore, we suggest less aggressive procedures to treat children with hydronephrosis.

Adolescent↗

PubMed1996

In vivo CAMPATH-1 followed by T cell-depleted bone marrow transplantation: a potential new mode of therapy for hepatitis-associated severe aplastic anemia (SAA).

Bone marrow transplantation (BMT) has been previously reported as a successful mode of treatment for hepatitis B and associated severe aplastic anemia (SAA). Non-A, non-B, non-C hepatitis is one of the causes of SAA. The etiology of SAA caused by non-A, non-B, non-C hepatitis is unknown. There is evidence that the immune response and, specifically, T cells and monocytes have a major role in both HCV- and HBV-induced liver damage. The liver damage caused by non-A, non-B, non-C hepatitis may be associated with similar mechanisms. We describe an 8-year-old girl who developed SAA post-non-A, non-B, non-C hepatitis infection. She was treated by in vivo CAMPATH-1G antibodies followed by T cell depleted HLA-matched BMT and cyclosporin A, resulting in gradual improvement and almost normalization of liver function. We suggest that treatment with CAMPATH-1G followed by T cell-depleted BMT and cyclosporin A could be a novel mode of therapy for viral non-A, non-B, non-C hepatitis-induced liver damage and associated SAA.

Anemia, Aplastic↗

PubMed1996

Activated allogeneic cell therapy (allo-ACT) for relapsed chronic myelogenous leukemia (CML) refractory to buffy coat transfusions post-allogeneic bone marrow transplantation.

We describe a 17-year-old male patient with chronic myelogenous leukemia (CML) in hematologic and cytogenetic relapse 4 months post-non-T cell-depleted allogeneic bone marrow transplantation for accelerated CML. Two sequential buffy coat transfusion with donor peripheral blood cells (8.9 and 4.8 x 10(7) cells/kg), the second transfusion in combination with in vivo activation of donor cells by human recombinant interleukin-2 (rIL-2) 6 x 10(6) IU/m2 subcutaneously for 3 days, failed to induce remission . The patient responded to an infusion of donor peripheral blood lymphocytes (3.4 x 10(7) cells/kg) pre-activated in vivo with rIL-2 and additionally activated in vivo with rIL-2, 6 x 10(6) IU/m2/day subcutaneously for 3 days. Elimination of the Philadelphia (Ph) clone was confirmed by cytogenetic analysis showing a normal male karyotype and by disappearance of the bcr/abl transcript, using the polymerase chain reaction (PCR). At present, the patient is 26 months post-treatment with no evidence of disease, but with chronic graft-versus-host disease. Our data indicate that allogeneic activated cell therapy (allo-ACT) may provide antitumor effector cells that successfully induce graft-versus-leukemia (GVL) effects even when cell therapy with donor buffy coats was insufficient.

Adolescent↗

PubMed1996

Allogeneic cell-mediated immunotherapy using donor lymphocytes for prevention of relapse in patients treated with allogeneic bone marrow transplantation for hematological malignancies.

Two major causes of treatment failure in allogeneic BMT for leukemia are graft versus host disease (GVHD) and leukemic relapse. Acute GVHD, mediated by alloreactive donor T lymphocytes originating from the transfused marrow is the most significant cause of transplant-related morbidity and mortality, despite the use of combined prophylaxis with cyclosporine and methotrexate. Effective prevention of GVHD can be accomplished by depletion of donor immunocompetent T cells from the marrow prior to its infusion. Depletion of lymphocytes, however, prevents the immune mediated interaction of donor T cells against residual host tumor cells--the graft versus leukemia (GVL) effect, which significantly contributes to the curative effect of allogeneic BMT. It is still unsettled to what extent GVH and GVL are unseparable or closely related phenomena, and a major question remains whether it would be possible to retain the beneficial antileukemic effects of donor T cells and at the same time prevent or control the risk of GVHD. We have adopted a policy by which an allogeneic BMT is conducted with T cell depleted marrow to minimize the risk of severe acute GVHD, followed by stepwise administration of fresh unirradiated donor lymphocytes for prevention of leukemic relapse. Our data show that the overall relapse free survival was significantly better for patients receiving preventive posttransplant donor lymphocytes, predominantly when transplant was performed in 1st or 2nd CR.

Adolescent↗