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E J Kanfer

Publications and source records attributed to E J Kanfer.

27 records · Page 2Linked to original sources

Graft-versus-leukaemia following allogeneic bone marrow transplantation: emergence of cytotoxic T lymphocytes reacting to host leukaemia cells.

Cytotoxic T lymphocyte precursor (CTLp) frequency assays were examined in patients with chronic myeloid leukaemia (CML) following bone marrow transplantation (BMT) using recipient lymphocytes or CML cells as targets in a 51Cr release cytotoxicity assay. Eighteen patients were studied; 11 received marrow from a fully HLA A, B and DR matched sibling donor, and six from matched unrelated donors or a partially matched sibling (one patient). Two of the unrelated donor transplant recipients received marrow depleted of T lymphocytes, and the remainder received unmanipulated marrow and cyclosporin with or without methotrexate as prophylaxis against graft-versus-host disease (GVHD). Donor cells tested before BMT did not generate CTL against the patients' leukaemia, but up to 9 months after BMT a low frequency of CTLp directed against the patients' CML cells (Lk-CTLp) was detected in all patients. The Lk-CTLp frequency was significantly lower than the frequency of CTLp directed against the recipients' PHA transformed pretransplant lymphocytes (Ly-CTLp) (p less than 0.05). Lk-CTLp showed MHC restricted cytotoxicity and did not demonstrate cytotoxicity in an NK assay. The Lk-CTLp frequency correlated with both GVHD severity and relapse: severe GVHD was only seen with Lk-CTLp frequencies greater than 1:400,000, while leukaemic relapse was only observed in two patients with Lk-CTLp frequencies less than 1:400,000. These results show that a low frequency of alloreactive cells of presumed donor origin with cytotoxic potential against residual leukaemia normally circulate after BMT. Their relationship with the graft-versus-leukaemia phenomenon and their cross-reaction with GVHD reacting cells remain to be determined.

Adolescent↗

Thalidomide for the therapy of graft-versus-host disease following allogeneic bone marrow transplantation.

The immunosuppressive effects of the sedative drug thalidomide have been utilised in a variety of immune disorders. In the present study, 6 patients were treated who developed graft-versus-host disease (GvHD) following allogeneic bone marrow transplantation (BMT) with thalidomide and in a dose range of 200-600 mg daily. Two of 3 patients with chronic GvHD showed clear improvement, whereas none of the 3 patients with acute GvHD derived unequivocal benefit. Although based on a small number of patients, these data suggest that thalidomide may find a useful place in the therapy of GvHD, perhaps specifically in the chronic form of this disorder.

Adolescent↗

Bone marrow transplantation: current controversies.

The 1988 UCLA symposium on bone marrow transplantation (BMT) provided a comprehensive overview of the current position of this therapy in its widest sense. Major consideration was given to the role of BMT in the treatment of the acute and chronic leukaemias, with particular reference to the timing of this procedure in these disorders. The use of autologous grafting in haematological and non-haematological malignancy was discussed, and the results of BMT in aplastic anaemia and the inherited immune and metabolic diseases were presented. The prevention and therapy of the major post-transplant complications, cytomegalovirus interstitial pneumonitis and graft-versus-host disease, were the subject of lengthy deliberations as were the related topics of T cell depletion, graft-versus-leukaemia and the use of partially matched related or matched unrelated donors.

Anemia, Aplastic↗

Venocclusive disease of the liver after chemoradiotherapy and autologous bone marrow transplantation.

We determined the incidence of venocclusive disease of the liver (VOD) in 96 recipients of autologous bone marrow transplants (BMT) to be 9.4%, a figure less than that reported for allogeneic transplantation. The development of VOD was compared in a cohort of 21 autologous BMT recipients and in 56 randomly chosen, comparably conditioned, concurrent allogeneic BMT recipients. One of these 21 (4.8%) autologous recipients developed VOD, versus 14 of 56 (25%) allogeneic recipients (P less than 0.05). Logistic regression analysis confirmed pretransplant hepatocellular dysfunction as a risk factor for VOD, and suggested that the use of methotrexate and/or cyclosporine contributes to the development of VOD after chemoradiation therapy. However, a graft-versus-host reaction cannot be excluded as a cause of the higher incidence of VOD in allogeneic recipients.

Adolescent↗

Allogeneic and syngeneic marrow transplantation following high dose dimethylbusulfan, cyclophosphamide and total body irradiation.

Fifty-eight patients received an allogeneic or syngeneic marrow transplant following conditioning with high doses of dimethylbusulfan (DMB), cyclophosphamide (CY) and total body irradiation (TBI). Thirty-two patients had either chronic myeloid leukemia (CML) in accelerated phase or blast transformation, or acute leukemia after first relapse. The actuarial survival of these 32 patients at 3 years was 12% compared with 25% for a group of 206 patients with similar diagnoses prepared for transplantation with CY and TBI alone. This reduced survival was associated with a greater incidence of early non-leukemic deaths, in particular as a result of severe hepatic veno-occlusive disease. The incidence of leukemic relapse was not different in the two groups. Of 13 patients with CML in chronic phase who received syngeneic transplants following DMB, CY and TBI, nine are alive in hematologic and cytogenetic remission from 3.9 to 9.4 (median 6.2) years post-transplant.

Adolescent↗