thioguanine-anhydrous and Candidiasis

Topics: ABO Blood-Group System; Adolescent; Adult; Bone Marrow Cells; Bone Marrow Transplantation; Candidiasis; Child; Cyclophosphamide; Cytarabine; Cytomegalovirus Infections; Daunorubicin; Graft vs Host Reaction; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Middle Aged; Radiation Chimera; Thioguanine; Transplantation, Homologous

A 19-yr-old boy has been in continuous complete remission from acute myelogenous leukemia for 3 yr after allogeneic bone marrow transplantation prepared with combination chemotherapy. During the first year post-transplant, however, the patient developed near-fatal graft-versus-host reaction followed by 11 severe viral and bacterial infections. Immune evaluation during this period revealed multiple defects which were not present prior to transplantation, nor present in the transplant donor: diminution of lymphoid tissue, decline of all immunoglobulin subtypes, deletion of secretory immunoglobulin, disappearance of isohemagglutinins, loss of antibody to diptheria and tetanus toxoids, cessation of cutaneous hypersensitivity to mumps antigen, and inhibition of serum opsonizing activity. The patient was also unable to develop normal humoral or cellular reactivity to brucella antigen, keyhole limpet hemocyanin, or dinitrochlorobenzene. This patient's course illustrates the severity and chronicity of immunoincompetence associated with allogeneic marrow grafting, the importance of early detection and rigorous treatment of infectious disease in these patients, and the need for improved immunologic reconstitution in human marrow transplantation. It also indicates that complete recovery from the immune defects is possible, and that long-term remission from acute myelogenous leukemia can be achieved with allogeneic marrow transplantation.

Topics: ABO Blood-Group System; Adolescent; Adult; Anti-Bacterial Agents; Antilymphocyte Serum; B-Lymphocytes; Bacterial Infections; Blood Group Incompatibility; Bone Marrow Cells; Bone Marrow Transplantation; Candidiasis; Cyclophosphamide; Cytarabine; Graft vs Host Reaction; Histocompatibility Antigens; Humans; Immunity, Maternally-Acquired; Immunologic Deficiency Syndromes; Leukemia, Myeloid, Acute; Male; Nitrosourea Compounds; Opsonin Proteins; T-Lymphocytes; Thioguanine; Transplantation, Homologous; Virus Diseases

16 courses of an 8-drug regimen including daunomycin, vincristine, cytosinearabinoside, thioguanine, methotrexate, cyclophosphamide, prednisolone and hydroxyurea, and 12 courses of a 7-drug regimen including the same drugs minus hydroxyurea were administered in 16 otherwise therapy-resistant cases of acute myeloid leukaemia. In spite of a significant and rapid reduction of the leukaemic cell-mass in all the cases treated, only two brief minimal remissions were obtained. The main toxic effect was myelosuppression. However, the treatment was associated with a high frequency of mucosal ulcerations of the oesophagus and stomach, and it cannot be excluded that the latter complication may be drug-related.

Topics: Adolescent; Adult; Aged; Candidiasis; Cyclophosphamide; Cytarabine; Daunorubicin; Drug Resistance; Drug Therapy, Combination; Esophagitis, Peptic; Female; Humans; Hydroxyurea; Leukemia, Myeloid, Acute; Leukocyte Count; Leukopenia; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisolone; Stomach Ulcer; Thioguanine; Vincristine

Implications and course of fever were evaluated during hospitalization of 24 patients with acute myelogenous leukemia. Forty-five febrile episodes were identified. Fever present at admission was usually associated with a diagnosable and treatable infection; fever shortly after induction was self-limited; and fever during granulocytopenia was more likely to be associated with bacteremia. Bacteremia and pneumonia were the most common types of infection. Only Gram-negative bacteria and Candida were identified as causes of infection during life, with Pseudomonas and Klebsiella the most frequently isolated pathogens. Invasive candidiasis was a major postmortem finding. A delay in initiation of empirical treatment beyond the third day of fever was associated with an increase in mortality as was continuation of treatment for longer than 14 days.

Topics: Agranulocytosis; Anti-Bacterial Agents; Candidiasis; Cytarabine; Daunorubicin; Fever; Humans; Klebsiella Infections; Leukemia, Myeloid, Acute; Pseudomonas Infections; Thioguanine