https://ebmt.co.uk/wp-content/uploads/2013/08/GVHD1.pdf

National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. Diagnosis and Staging Working Group Report

Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel

BACKGROUND: The cause of chronic myeloid leukemia (CML) is a constitutively active BCR-ABL tyrosine kinase. Imatinib inhibits this kinase, and in a short-term study was superior to interferon alfa ...

/pdf/five-year-follow-up-of-patients-receiving-imatinib-for-2ejt1h30j2.pdf

Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia

http://caprockhematology.com/Site/AML_and_ALL_files/AML%20Review%20Blood%202010.pdf

Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet.

Publisher Summary Studies of cytotoxicity by human lymphocytes revealed not only that both allogeneic and syngeneic tumor cells were lysed in a non-MHC-restricted fashion, but also that lymphocytes from normal donors were often cytotoxic. Lymphocytes from any healthy donor, as well as peripheral blood and spleen lymphocytes from several experimental animals, in the absence of known or deliberate sensitization, were found to be spontaneously cytotoxic in vitro for some normal fresh cells, most cultured cell lines, immature hematopoietic cells, and tumor cells. This type of nonadaptive, non-MHC-restricted cellmediated cytotoxicity was defined as “natural” cytotoxicity, and the effector cells mediating natural cytotoxicity were functionally defined as natural killer (NK) cells. The existence of NK cells has prompted a reinterpretation of both the studies of specific cytotoxicity against spontaneous human tumors and the theory of immune surveillance, at least in its most restrictive interpretation. Unlike cytotoxic T cells, NK cells cannot be demonstrated to have clonally distributed specificity, restriction for MHC products at the target cell surface, or immunological memory. NK cells cannot yet be formally assigned to a single lineage based on the definitive identification of a stem cell, a distinct anatomical location of maturation, or unique genotypic rearrangements.

Biology of natural killer cells.

Bone-marrow transplantation in high-risk acute lymphoblastic leukaemia in first and second remission

A survey of the results of bone marrow transplantation for severe aplastic anaemia in 13 European teams is reported. 159 questionnaires were analysed by univariate and multivariate analysis. The overall 1 year survival was 41.2%. The chance of survival was decreased by the presence of infection before grafting and by the use of female donors. The conditioning regimen did not influence survival. Graft rejection was influenced by the conditioning regimen and the sex of the donor. Graft-versus-host disease was influenced by the conditioning regimen, and the age and the sex of the recipient. This study defines prognostic indices which may be helpful in determining the likelihood of success after marrow transplantation for severe aplastic anaemia.

Bone Marrow Transplantation in Severe Aplastic Anaemia: a Survey of the European Group for Bone Marrow Transplantation (E.G.B.M.T.) *

Hypersensitivity pneumonitis related to imatinib mesylate.

Prophylaxis against toxoplasmosis with weekly administration of pyrimethamine/sulfadoxine (Fansidar) was assessed for efficacy and toxicity in bone marrow transplant (BMT) recipients over a 21 month period. Sixty-nine of 90 consecutive seropositive patients were evaluable. Fansidar was administered from the time of established engraftment (median day 40, range days 13-100). Medication was scheduled to be continued until 6 months or longer in cases of continued immunosuppression (median 10 months, range day 72 to 22 months). No proven case of toxoplasmosis occurred in patients receiving prophylaxis. In addition, there were no cases of Pneumocystis carinii. Side-effects included BM suppression requiring cessation (n = 4) or interruption (n = 8) of therapy and rash (n = 1). To evaluate toxicity associated with prolonged therapy, 42 evaluable patients were assessed at 6 months following transplant (or at least 4 months of continuous treatment). Haematological toxicity was minimal and compounded in three patients showing moderate derangement by cytomegalovirus infection and graft-versus-host disease. Fansidar is an effective prophylactic agent against toxoplasmosis in BMT patients.

Prophylaxis of toxoplasmosis infection with pyrimethamine/sulfadoxine (Fansidar) in bone marrow transplant recipients.

Our objective was to study the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) for Shwachman-Diamond Syndrome (SDS). Among 71 SDS patients included in the French Severe Chronic Neutropenia Registry, 10 received HSCT between 1987 and 2004 in five institutions. The indications were bone marrow failure in five cases, and myelodysplastic syndrome (MDS) or leukemia in five cases. The median follow-up of patients who survived without relapse is 6.9 years (3.1-16.8 years). The conditioning regimen consisted of a busulfan-cyclophosphamide combination (n=6) or total body irradiation plus chemotherapy (n=4). Six patients received stem cells from unrelated donors and four from identical siblings. Engraftment was complete in eight patients and unassessable in two patients. These latter two patients died of infections 32 and 36 days after HSCT, with grade IV graft-versus-host disease and multiorgan dysfunction. A third patient died from an acute respiratory distress syndrome 17 months after HSCT with progressive granulocytic sarcoma. One patient had an MDS relapse 4 months after HSCT and died 10 months later. The overall 5-year event-free survival rate is 60+/-15%. We conclude that HSCT is feasible for patients with SDS who develop bone marrow failure or malignant transformation.

/pdf/hematopoietic-stem-cell-transplantation-for-shwachman-2xdo2nkatp.pdf

Eliane Gluckman

Papers

Bone-marrow transplantation in high-risk acute lymphoblastic leukaemia in first and second remission

Bone Marrow Transplantation in Severe Aplastic Anaemia: a Survey of the European Group for Bone Marrow Transplantation (E.G.B.M.T.) *

Hypersensitivity pneumonitis related to imatinib mesylate.

Prophylaxis of toxoplasmosis infection with pyrimethamine/sulfadoxine (Fansidar) in bone marrow transplant recipients.

Hematopoietic stem cell transplantation for Shwachman-Diamond syndrome: experience of the French neutropenia registry