Excellent long-term survival after allogeneic marrow transplantation in patients with severe aplastic anemia.

Between 1982 and 1996, 20 patients (10 male, 10 female) with severe aplastic anemia (SAA) with a median age of 25 years (17-37 years), received grafts from an HLA-identical sibling (n = 17), HLA-identical unrelated donor (n = 2) or identical twin (n = 1). The median time from diagnosis to marrow transplantation (BMT) was 15 months (range 1-96 months). More than half of the patients had received more than 10 units of red blood cells or platelet transfusions prior to BMT. Pretransplant immunosuppression consisted of cyclophosphamide (CY) alone (n = 10), CY in combination with total body irradiation (n = 8), and CY and antithymocyte globulin (n = 2). For graft-versus-host disease (GVHD) prophylaxis methotrexate (MTX) alone (n = 9) or MTX with cyclosporin A (n = 10) were given. One patient died on day 18 after marrow grafting due to infection; all other patients had complete and sustained engraftment (95%). Eight patients developed acute GVHD (42%), nine patients chronic GVHD (53%) including four with extensive disease manifestation. One patient experienced a secondary malignancy 11 years after BMT. Eighteen patients followed for a median of 9.45 years (0.42-14.7 years) have sustained hematological reconstitution and are alive and well with a Karnofsky performance score of at least 90%. Thus, excellent long-term survival and low morbidity make allogeneic or syngeneic BMT the treatment of choice for younger patients with severe aplastic anemia.

Jarisch-Herxheimer reaction in a patient with neurosyphilis.

A 40 year old man presented with progressive personality changes in the previous six months. Specific serological tests for syphilis in blood and CSF were highly positive and CSF sedimentation showed signs of an inflammatory process. Ten hours after the start of penicillin treatment a severe symptomatic Jarisch-Herxheimer reaction with alteration of level of consciousness, pupillary changes, and focal neurological signs developed. Jarisch-Herxheimer reaction may occur in various settings, particularly in the treatment of syphilis. Investigation of CSF before the treatment may predict a potential risk. Corticosteroid treatment has been suggested for prevention.

Fatal encephalitis in a patient with chronic graft-versus-host disease.

A 32-year-old male patient with chronic myelocytic leukemia in accelerated phase received a bone marrow allograft from his 42-year-old HLA/MLC-identical sister. He recovered from acute graft-versus-host disease (GVHD) grade III-IV of skin, liver and gut, but chronic GVHD of progressive onset developed. On day 556 post-graft severe thrombocytopenia was resistant to prednisolone, cyclophosphamide and high dose immunoglobulin. Splenectomy was followed by a normalization of platelet counts. The subsequent clinical course was characterized by progressive muscular atrophy and weight loss. Dysphagia, dysarthria, cachexia and ultimately recurrent pneumonic episodes ensued. The cachectic patient developed a highly abnormal breathing pattern with hypoventilation and intermittent apnea requiring mechanical ventilation. Auditory evoked potentials revealed a considerable dysfunction of the brainstem. The patient died on day 1120 post-graft from pneumonia, aggravated by thoracic muscular insufficiency. Postmortem examination revealed diffuse predominantly lymphoid perivascular infiltration in meninges and CNS tissue; proliferation of activated microglial cells expressing the HLA-DR antigen was prominent in the brainstem. These histologic changes are similar to those observed in the CNS in experimental GVHD. We suggest that this case represents the first documentation of CNS involvement in chronic GVHD.