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Y Kapelushnik

Publications and source records attributed to Y Kapelushnik.

8 recordsLinked to original sources
PubMed1998

Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases.

Myeloablative conditioning associated with hazardous immediate and late complications is considered as a mandatory first step in preparation for allogeneic blood or marrow transplantation (allogeneic BMT) for the treatment of malignant hematologic disorders and genetic diseases. Immune-mediated graft-versus-leukemia (GVL) effects constitute the major benefit of allogeneic BMT. Therefore, we have introduced the use of relatively nonmyeloablative conditioning before allogeneic BMT aiming for establishing host-versus-graft tolerance for engraftment of donor immunohematopoietic cells for induction of GVL effects to displace residual malignant or genetically abnormal host cells. Our preliminary data in 26 patients with standard indications for allogeneic BMT, including acute leukemia (n = 10); chronic leukemia (n = 8), non-Hodgkin's lymphoma (n = 2), myelodysplastic syndrome (n = 1), multiple myeloma (n = 1), and genetic diseases (n = 4) suggest that nonmyeloablative conditioning including fludarabine, anti-T-lymphocyte globulin, and low-dose busulfan (8 mg/kg) is extremely well tolerated, with no severe procedure-related toxicity. Granulocyte colony-stimulating factor mobilized blood stem cell transplantation with standard dose of cyclosporin A as the sole anti-graft-versus-host disease (GVHD) prophylaxis resulted in stable partial (n = 9) or complete (n = 17) chimerism. In 9 patients absolute neutrophil count (ANC) did not decrease to below 0.1 x 10(9)/L whereas 2 patients never experienced ANC < 0.5 x 10(9)/L. ANC > or = 0.5 x 10(9)/L was accomplished within 10 to 32 (median, 15) days. Platelet counts did not decrease to below 20 x 10(9)/L in 4 patients requiring no platelet support at all; overall platelet counts > 20 x 10(9)/L were achieved within 0 to 35 (median 12) days. Fourteen patients experienced no GVHD at all; severe GVHD (grades 3 and 4) was the single major complication and the cause of death in 4 patients, occurring after early discontinuation of cyclosporine A. Relapse was reversed by allogeneic cell therapy in 2/3 cases, currently with no residual host DNA (male) by cytogenetic analysis and polymerase chain reaction. To date, with an observation period extending over 1 year (median 8 months), 22 of 26 patients (85%) treated by allogeneic nonmyeloablative stem cell transplantation are alive, and 21 (81%) are disease-free. The actuarial probability of disease-free survival at 14 months is 77.5% (95% confidence interval, 53% to 90%). Successful eradication of malignant and genetically abnormal host hematopoietic cells by allogeneic nonmyeloablative stem cell transplantation represents a potential new approach for safer treatment of a large variety of clinical syndromes with an indication for allogeneic BMT. Transient mixed chimerism which may protect the host from severe acute GVHD may be successfully reversed postallogeneic BMT with graded increments of donor lymphocyte infusions, thus resulting in eradication of malignant or genetically abnormal progenitor cells of host origin.

Adolescent↗
PubMed1996

dup(10q) lacking alpha-satellite DNA in bone marrow cells of a patient with acute myeloid leukemia.

A marker chromosome was identified in leukemic cells on an AML patient. The G-banding pattern resembled on i(10q), but its centromeric position was not clear; in some cells it had a telocentric shape, in others a metacentric or acentric shape. The origin of the marker chromosome was confirmed by FISH, using chromosome-10-specific painting. To determine the centromeric position, C-banding and alpha-satellite probes were applied in FISH, and none of them gave a positive signal. Despite the absence of the centromeric alpha-satellite sequences and the constricted feature of the centromere, the essential centromeric activity was retained in this chromosome, namely, the separation of sister chromatids in anaphase.

Adolescent↗
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↗
PubMed1994

Cytomegalovirus pneumonia prior to engraftment following T-cell depleted bone marrow transplantation.

CMV pneumonia is a frequent complication of allogeneic bone marrow transplantation (BMT). It usually appears 23 months following transplantation and is associated with a high mortality rate. The incidence of CMV pneumonia in our T-lymphocyte depleted allogeneic BMT recipients, transplanted between 1987-1991, was 18 out of 197 (9.2%) patients. In 3 patients (1.5% of allogenic BMT recipients), pneumonia occurred prior to marrow engraftment, on days 12-16 post BMT. These patients did not develop acute GVHD in contrast to 9/11 patients who had acute GVHD in addition to developing CMV pneumonia between engraftment and day +100 (p < 0.03). Furthermore, these three patients did not receive steroid therapy as opposed to 14/15 patients who were treated with steroids and eventually contracted CMV pneumonia post-engraftment (p < 0.01). The three patients did not have two additional risk factors known for the development of CMV pneumonia: increasing age and a diagnosis of acute myeloblastic leukemia (AML) as the primary disease. Despite prompt diagnosis and therapy with ganciclovir and high doses of intravenous immunoglobulin (IVIG), two of the patients died. Tcell depleted BMT may be a risk factor for development of CMV pneumonia occurring prior to engraftment. In the era of post-BMT anti CMV prophylaxis, one should be aware that life-threatening CMV pneumonia may appear prior to engraftment and consider aggressive CMV prophylaxis.

Adolescent↗
PubMed1992

Immunotherapy of minimal residual disease in conjunction with autologous and allogeneic bone marrow transplantation (BMT).

Recent investigations in animal models of human lymphoid and myeloid leukemia suggest that induction of immune-mediated antitumor effects is feasible at the stage of minimal residual disease (MRD) using allogeneic immunocompetent lymphocytes following initial reconstitution with T cell depletion and/or activation of reconstituting syngeneic or allogeneic immune cells by recombinant interleukin-2 (rIL2). Pilot clinical trials in patients with leukemias and lymphomas at high risk to relapse following autologous bone marrow transplantation (BMT) suggest that beneficial antitumor effects may be achieved at the stage of MRD by home immunotherapy as soon as hematopoietic reconstitution occurs using rIL2 (Cetus) and alpha interferon (Roferon A) (Hoffmann LaRoche). Although results obtained from our open trial seem encouraging, prospective randomized trials and longer observation periods are needed in order to confirm immune-mediated antitumor effects in conjunction with autologous BMT in patients with malignant hematological disorders at high risk to relapse. Likewise, it seems that amplification of anti-leukemia effects following allogeneic BMT is feasible by post-transplant infusion of donor's peripheral blood lymphocytes for prevention and/or treatment of relapse.

Adolescent↗