Successful treatment of relapsed T-cell non-Hodgkin's lymphoma with allogeneic peripheral blood stem cell transplantation with double conditioning.

We report a patient with T-cell non-Hodgkin's lymphoma (NHL) who relapsed after treatment with relatively intensive third-generation chemotherapy, VACOP-B, and who was safely and effectively treated with allogeneic peripheral blood stem cell transplantation (allo PBSCT) with double conditioning. The first conditioning consisted of carboplatin and etoposide. Twenty-one days later, the second conditioning was performed with cytosine arabinoside, cyclophosphamide, and total body irradiation (AraC/Cy/TBI). Between the periods of the first and second conditioning, autologous (auto) PBSCT (4.4 x 10(5) colony-forming units granulocyte/macrophage (CFU-GM)/kg, 3.8 x 10(6) CD34+ cells/kg) was performed to rescue marrow aplasia after the first conditioning. After the second conditioning, allo PBSCT (2.1 x 10(5) CFU-GM/kg, 8.2 x 10(6) CD34+ cells/kg) was performed from a human leukocyte antigen-identical sibling. Marrow reconstitution after allo PBSCT was rapid. Grade I acute graft-vs.-host disease (GVHD) involving skin and chronic GVHD on the eye was observed. No severe transplantation-related complications occurred. With a follow-up of 22 months after allogeneic PBSCT, the patient is alive without evidence of the disease. This case shows that allo PBSCT with intensive double conditioning may become a new treatment strategy to achieve long-term disease-free survival for young NHL patients of resistant relapse with a great deal of tumor burden and invasion of lymphoma cells in bone marrow.

High incidence of chemotherapy-induced acral erythema in female patients with non-Hodgkin's lymphoma treated with the VACOP-B regimen.

Seven patients, all females out of 29 with non-Hodgkin's lymphoma (NHL) (16 males and 13 females) treated with the VACOP-B regimen utilizing granulocyte-colony-stimulating factor (G-CSF) support developed chemotherapy-induced acral erythema (CAE). In contrast, none of 32 patients with NHL who were treated with CHOP, MACOP-B, or biweekly CHOP regimens without G-CSF developed CAE. Total dose intensities of VACOP-B regimen were higher than those of the three other regimens. However, no significant difference in dose intensities of each drug in the patients treated with the VACOP-B regimen was found between male and female patients and between female patients with or without CAE. The cause of the high incidence of CAE (7/13) in the female patients treated with VACOP-B regimen remains unknown. However, female sex hormones may increase susceptibility to CAE. Since the occurrence of CAE interrupts intensive chemotherapy and reduces the cure rate, high risk patients for CAE should be carefully monitored for early symptoms and signs of CAE and should be treated early and appropriately.

Absence of fetal liver hematopoiesis in mice deficient in transcriptional coactivator core binding factor beta.

Core binding factor beta (CBF beta) is considered to be a transcriptional coactivator that dimerizes with transcription factors core binding factor alpha 1 (CBFA1), -2, and -3, and enhances DNA binding capacity of these transcription factors. CBF beta and CBFA2, which is also called acute myeloid leukemia 1 gene, are frequently involved in chromosomal translocations in human leukemia. To elucidate the function of CBF beta, mice carrying a mutation in the Cbfb locus were generated. Homozygous mutant embryos died between embryonic days 11.5-13.5 due to hemorrhage in the central nervous system. Mutant embryos had primitive erythropoiesis in yolk sac but lacked definitive hematopoiesis in fetal liver. In the yolk sac of mutant embryos, no erythroid or myeloid progenitors of definitive hematopoietic origin were detected, and the expression of flk-2/flt-3, the marker gene for early precursor cells of definitive hematopoiesis, was absent. These data suggest that Cbfb is essential for definitive hematopoiesis in liver, especially for the commitment to early hematopoietic precursor cells.

[The analysis of leukemic relapse after allogeneic bone marrow transplantation].

This report presents the analysis of leukemic relapse of 52 patients who received allogeneic bone marrow transplantation between July 1984 and May 1990. Conditioning regimen consisted of TBI + CY and GVHD prophylaxis consisted of cyclosporin-A and methotrexate. The relapse ratios of chronic myelogenous leukemia (CML) (21 in chronic phase, 1 in accelerated phase, 1 in blastic crisis), acute nonlymphocytic leukemia (ANLL) (all 17 in 1st CR), acute lymphocytic leukemia (ALL) (all 12 in 1st CR) were 13%, 18%, 25%, respectively, and 3 year disease free survival (DFS) was as follows, CML 68%, ANLL 72%, ALL 49%. Regarding acute GVHD grading and chronic GVHD presence, 3 year DFS was as follows, acute GVHD 0 degree: 59%, I degree: 78%, II degree-IV degree: 53%, chronic GVHD (+): 82% GVHD (-): 77%. In our center leukemic relapse has been the major cause of death after BMT since 1984. Among 9 relapsed cases, one recurred more than 3 years after BMT, and another one got recurrent leukemia of donor origin.

Clinical effect of granulocyte colony-stimulating factor on neutrophils and leukemic cells in myelogenous leukemia: analysis.

Clinical experiences with recombinant granulocyte colony-stimulating factor (rhG-CSF) in 13 acute (AML) and four chronic (CML) myelogenous leukemia patients are reported. Sixteen patients received rhG-CSF in support of treatment for life threatening infections and one CML patient in support of induction chemotherapy. After their first induction chemotherapy, six out of eight AML patients showed a rapid increase of neutrophils, recovered from infections and achieved complete remission (CR). One patient, in whom both neutrophils and blasts had increased during rhG-CSF administration, achieved CR through the next administration of chemotherapy (CR rate 87.5%). The last of the eight AML patients showed no increase of neutrophils, and died of interstitial pneumonitis. Two of five AML patients who received rhG-CSF after reinduction chemotherapy for relapsed or refractory leukemia achieved CR, a rate of 40%. In one of the two, the administration of rhG-CSF prior to induction chemotherapy seemed advantageous in achieving CR. During rhG-CSF administration, an increase of blastic cells in peripheral blood was observed in four out of all 13 AML patients. One of three CML patients, with a lymphoid crisis, showed an increase only of neutrophils, and recovered from infection. The other two showed increases of both neutrophils and blasts. One patient with CML in blastic crisis, undergoing induction chemotherapy with rhG-CSF administration, returned to the chronic phase. These clinical experiences suggest rhG-CSF to be effective in supporting infection therapy and in possibly enhancing the sensitivity of myelogenous leukemic blasts to antileukemic agents.

[A case of CA19-9 producing adenocarcinoma of the lung associated with idiopathic interstitial pneumonia].

A 63-year-old female, who had been suffering from idiopathic interstitial pneumonia (IIP) since two years and four months previously, was admitted with general fatigue, body weight loss, bloody sputum and progression of dyspnea. Chest roentgenogram on admission showed diffuse coarse ring shadows in the right middle and lower lung fields and in the left middle lung filed. Chest CT clearly showed honeycombing in bilateral dorso-basal segments of the lung. Serum CA19-9 level was elevated, and continued to increase during her clinical course. Sputum cytology was positive. Autopsy showed papillary adenocarcinoma of the lung (alveolar cell type). Immunohistochemical study of lung tissue showed positive CA19-9 staining on the surface of adenocarcinoma cells.