Helmut Diedrich

Recombinant human interferon (IFN) alpha-2b in chronic myelogenous leukaemia: dose dependency of response and frequency of neutralizing anti-interferon antibodies

Summary. Twenty‐seven patients with Philadelphia chromosome positive chronic myelogenous leukaemia in the chronic phase were treated with low doses of recombinant interferon (IFN) alpha‐2b. Ten patients entered a complete and six a partial haematologic remission with a median duration of 5·8 and 9·1 months respectively. Five minor cytogenetic responses were observed. These results are inferior compared to other studies with higher interferon‐doses. Fever was an acute side effect after injection of IFN, limb pains and fatigue occurred protractedly. Haematologic side effects, nonspecific EEG changes, weight loss, and development of pulmonary infiltrates were observed in later periods of the treatment. Eight patients developed neutralizing anti‐IFN antibodies after 4·2–20·4 months (median 12·8 months). Anti‐IFN antibodies were associated with relapse or refractoriness to IFN treatment: five out of nine patients with rising WBC after initial fall had antibodies, while four did not. Two out of four patients with primary non‐response had IFN‐antibodies. These results may indicate a serious problem in the long‐term treatment of CML with recombinant interferon.

Limited efficacy of imatinib in severe pulmonary chronic graft-versus-host disease

To the editor:nnWe read with interest that Olivieri et al[1][1] observed complete or partial responses to imatinib 100 or 200 mg daily with improvement of lung function in 7 of 11 patients (64%) with pulmonary chronic graft-versus-host disease (cGVHD) of mild severity (lung function score [LFS] of

Tetramer monitoring to assess risk factors for recurrent cytomegalovirus reactivation and reconstitution of antiviral immunity post allogeneic hematopoietic stem cell transplantation

S. Borchers, S. Luther, U. Lips, N. Hahn, J. Kontsendorn, M. Stadler, S. Buchholz, H. Diedrich, M. Eder, U. Koehl, A. Ganser, E. Mischak‐ Weissinger. Tetramer monitoring to assess risk factors for recurrent cytomegalovirus reactivation and reconstitution of antiviral immunity post allogeneic hematopoietic stem cell transplantation.u2028Transpl Infect Dis 2011: 13: 222–236. All rights reserved

Expansion of recipient‐derived antiviral T cells may influence donor chimerism after allogeneic stem cell transplantation

Donor chimerism (DC) analysis is an important marker in the hematopoietic stem cell transplant follow‐up. Here, we present evidence for a possible relationship of infectious complications and declines in DC. We analyzed the DC in patients experiencing cytomegalovirus (CMV) reactivation. In addition, in some patients chimerism analyses of T‐cell subsets were performed. CMV‐specific cytotoxic T‐lymphocytes (CMV‐CTL) were monitored using human leukocyte antigen‐restricted multimer staining. Interestingly, CMV reactivation was accompanied by changes in DC in 11 of 67 patients transplanted. For example, DC declined in a cord blood recipient, in both total leukocytes and CD4 and CD8 T‐cell subsets upon CMV reactivation. The latter was controlled after only 5 days through expanding CMV‐CTL of 96% recipient origin, according to chimerism analysis of CMV‐CTL (enriched beyond 50%). In another patient, transplanted after reduced‐intensity conditioning from a DQB1 mismatched, CMV seronegative donor, incipient CMV reactivation was completely aborted by CMV‐CTL of recipient origin. However, at the same time, mixed chimerism dropped from 51% to 0% donor type, resulting in late graft rejection. Our data indicate that chimerism analyses in subset populations lead to a better understanding of declining total leukocyte chimerism. Furthermore, recipient‐derived CMV‐CTL may be able to control CMV reactivation after reduced‐intensity conditioning. We speculate that autologous CMV‐CTL may be instrumental to overcome recurrent CMV reactivations, especially in patients transplanted from CMV‐seronegative donors. In addition, the expansion of recipient‐derived CMV‐CTL may contribute to both, graft failure or to conversion to full DC.

Clinical Significance of Neutralizing Antibodies in Patients with Chronic Myelogenic Leukemia

The recombinant technology made it possible to produce large amounts of interferons (IFNs), to characterize different human IFN subtypes, and to exploit their therapeutic potential [1]. In 1981, nearly a decade after the introduction of IFNs into the clinic, Treuner was the first to recognize the development of IFN antibodies as a typical side effect of IFN treatment in humans. He reported on a patient with nasopharyngeal carcinoma who developed neutralizing IgG antibodies to IFN-β under IFN-β therapy.

Prospective Validation of a Chronic GvHD-Specific Proteome Pattern (cGvHD-MS14) Post Allogeneic Hematopoietic Stem Cell Transplantation

P002 HLA-haploidentical allografting with high-dose posttransplant cyclophosphamide: clinical outcomes and immune-reconstitution A. Busca, E. Maffini, F. Ferrando, C. Dellacasa, R. Pulito, E. Saraci, L. Giaccone, M. Boccadoro, P. Omedè, B. Bruno Division of Hematology, Department of Molecular Biotechnology and Health Sciences, University of Torino, A.O.U. Città della Salute e della Scienza di Torino, Torino, Italy