Arsenic trioxide in the treatment of a patient with multiply recurrent, ATRA-resistant promyelocytic leukemia: a case report.

PURPOSE: Little experience exists with the use of arsenic trioxide in the treatment of recurrent, all-trans retinoic acid (ATRA)-resistant, acute promyelocytic leukemia (APL). The authors report a patient with multiply recurrent APL treated with arsenic trioxide (As2O3), which was administered as recommended in the protocol from the People' s Republic of China. The results of this treatment and its toxicity are discussed. The available literature on arsenic therapy is reviewed. PATIENTS AND METHODS: The patient was a 15-year-old African-American girl with APL that had resisted conventional chemotherapy, ATRA therapy followed by autologous peripheral stem cell transplant, and a second course of ATRA induction therapy administered for relapse after transplant. The patient was treated with 10 mg As2O3 intravenously for 28 days. After a 4-week break, she received a second 28-day course of As2O3 therapy. RESULTS: After completion of the first 28-day course of As2O3 treatment, morphologic and cytogenetic remission occurred. Reverse-transcription polymerase chain reaction demonstrated persistence of the PML-RARalpha fusion transcript. After the second course of As2O3, the patient had a complete remission by morphologic, cytogenetic, and molecular criteria. Approximately 6 months after the end of two courses of As2O3 therapy, the patient again underwent relapse. An additional course of As2O3 achieved a morphologic, although not a cytogenetic or molecular, remission. CONCLUSIONS: As2O3 therapy produced remission in a patient with multiply relapsed, ATRA-resistant APL. Toxic side effects were minimal. The patient underwent relapse 6 months after this therapy. Further investigation will be necessary to determine the proper role of As2O3 therapy in patients with APL.

Pregnancy during therapy for childhood acute lymphoblastic leukemia: two case reports and a review of the literature.

PURPOSE: The incidence and consequences of pregnancy during therapy for childhood acute lymphoblastic leukemia (ALL) are largely unknown. To explore the issues involved in this complication of ALL treatment, two recent cases are presented. PATIENTS: Two 15-year-old girls with "high risk" ALL became pregnant while receiving maintenance therapy. RESULTS: In one case, the patient experienced a spontaneous abortion at approximately 5 to 6 weeks gestation. The patient completed maintenance therapy and is in remission 8 months after the end of treatment. The second patient, known to be non-compliant during therapy, was found to be 5 months pregnant at the end of maintenance therapy. She developed HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count), was induced at approximately 34 weeks, and delivered an apparently normal baby girl. Both the patient and her baby continue to do well 10 months after delivery. CONCLUSIONS: A variety of factors may influence the incidence of pregnancy during ALL therapy. Gonadal function, which is likely to return to normal during maintenance therapy, may also be affected by alterations in the dose intensity of treatment. Social factors may also alter the incidence of pregnancy. Adverse effects on the fetus are more likely to occur in the first trimester, depending on the drug or drugs used. Although all chemotherapies may have mutagenic and teratogenic effects, they do not invariably cause abnormalities. Survival of adolescents who become pregnant during treatment does not appear to be adversely affected when therapy is not modified or discontinued.

Long-term follow-up of a patient transplanted for Hunter's disease type IIB: a case report and literature review.

Unlike most other storage diseases and despite clinical experience, the indications for bone marrow transplantation in Hunter's disease remain controversial. The case of a 14-year-old male with mucopolysaccharidosis type IIB is presented, who received an allograft from his HLA-identical sibling. The donor had been off therapy for acute lymphoblastic leukemia for 3 years. The patient experienced minimal difficulties with his transplant and was fully engrafted by day 42, with no signs of acute or chronic graft-versus-host disease. Now, more than 3 years after BMT, the patient has experienced significant subjective and objective improvement in his disease. The iduronate-2-sulfatase levels in the serum are now approximately 10% of normal control. Urinary glycosaminoglycans were negative. The posttransplant marrow was evaluated for donor-recipient source using VNTR analysis with the polymerase chain reaction (PCR). This showed a PCR-detectable subpopulation of residual patient marrow cells remaining, suggesting a state of stable mixed chimerism. The patient continues to show signs of amelioration of his disease. These results may be of value in determining the proper therapy for a patient with mild Hunter's disease, and may also be pertinent to the future application of recombinant enzyme therapy or gene therapy.

Capnocytophaga bacteremia in a patient with Hodgkin's disease following bone marrow transplantation: case report and review.

Capnocytophaga is a gram-negative, capnophilic, facultatively anaerobic bacillus that normally inhabits the oral cavity. We report the case of a patient who developed capnocytophaga bacteremia following autologous bone marrow transplantation for Hodgkin's disease, and we review other reported cases of capnocytophaga bacteremia in immunocompromised patients. In our case infection followed pretransplantation conditioning and was associated with severe oral mucositis and neutropenia. Antibiotic therapy resulted in clinical resolution of infection. Capnocytophaga bacteremia should be included in the differential diagnosis of febrile neutropenia in immunocompromised patients (e.g., those undergoing bone marrow transplantation) especially in the presence of mucositis and gingival bleeding.

SUP-HD1: a new Hodgkin's disease-derived cell line with lymphoid features produces interferon-gamma.

A new cell line, SUP-HD1, was established from the pleural effusion of a patient with nodular sclerosing Hodgkin's disease (NSHD). The SUP-HD1 cells had the characteristic morphology of Reed-Sternberg cells and contained acid phosphatase and nonspecific esterase. The cells lacked the Epstein-Barr virus (EBV) genome and reacted with monoclonal antibodies (MoAbs) against CD15 (Leu-M1), CD25 (Tac), CD71 (OKT9), Ki67, and HLA-Dr. However, the SUP-HD1 cells were nonreactive with MoAbs that specifically identify T lymphocytes, B lymphocytes, and macrophage/myeloid cells. Karyotype analysis of the cell line showed clonal abnormalities involving 1p13, 7p15, 8q22, and 11q23, chromosomal locations, at which breakpoints have been reported in HD. Southern blot analysis demonstrated rearrangement of the immunoglobulin heavy chain and kappa light chain genes as well as the gene for the beta chain of the T-cell receptor (TCR). Transcriptional analysis showed expression of RNAs for kappa light chain, interferon-gamma (IFN-gamma), and interleukin-2 receptor (IL-2R) but not IL-2. The SUP-HD1 cells lacked cytoplasmic and surface immunoglobulin heavy chain, but a small amount of cytoplasmic kappa light chain was detected. The presence of nuclear factor kappa B (NF kappa B), a B-lymphocyte-associated transcription factor, was demonstrated in stimulated and unstimulated cells. In addition, the SUP-HD1 cell line, produced IFN-gamma, a T-lymphocyte-associated lymphokine. Based on these data, the SUP-HD1 cells appear to be aberrant lymphocytes with characteristics of both activated B and T lymphocytes. Elaboration of lymphokines such as IFN-gamma by the malignant cells may represent one explanation for the unique clinical and pathologic features of HD.