Early recovery of host-derived hematopoiesis in marrow transplant recipients conditioned with high-dose busulfan and cyclophosphamide.

Three marrow transplant recipients with hematologic malignancies (two AML, one myelodysplastic syndrome) experienced prolonged pancytopenia after allogeneic BMT following conditioning with non-TBI regimens containing high-dose busulfan and cyclophosphamide (Bu/CY), despite the use of G-CSF. Early recovery of host-derived hematopoiesis ensued. Although neutrophil counts in these patients exceeded 500 x 10(6)/l by day 30 after transplant, these cells were of host origin. This early recovery of host-derived hematopoiesis has been observed rarely among patients conditioned with TBI-based regimens. When patients conditioned with Bu/CY show delayed hematologic recovery, mixed chimerism should be considered even in the presence of normal neutrophil recovery.

Allogeneic bone marrow transplantation as a therapeutic modality for hematological disorders: a report based on 39 cases.

The outcomes of 39 patients with hematological disorders who had undergone allogeneic bone marrow transplantation (BMT) from September 1986 to March 1992 were reported. The length of follow-up was six to 50 months. Twenty patients with acute leukemia, eight patients with aplastic anemia, seven patients with chronic myelogenous leukemia, two patients with non-Hodgkin's lymphoma, and two patients with myelodysplastic syndrome were included. Major complications were acute graft-versus-host disease (GVHD) (17 cases out of 36 evaluable cases; 47 percent), chronic GVHD (13/25; 52 percent), sepsis (20/41; 49 percent), interstitial pneumonitis (IP) (10/30; 33 percent), and veno-occlusive disease (VOD) of the liver (5/41; 12 percent). Acute and chronic GVHD were well managed with cyclosporin, methotrexate, and steroids. VOD of the liver seemed to be associated with the pretransplant regimen including busulfan and cyclophosphamide. The overall probability of disease free survival of 39 patients who had undergone allogeneic BMT was 0.56. This includes nine high risk cases such as HLA antigen mismatch between the donor and the recipient, and as in the second or subsequent remission or in relapsed cases. The probability of disease free survival in patients with acute leukemia, chronic myelogenous leukemia, and aplastic anemia including high risk cases was 0.55 (n = 20), 0.71 (n = 7), and 0.50 (n = 8) respectively. These results indicate that allogeneic BMT is the major therapeutic strategy for patients whose survival could not be expected by conventional chemotherapy and that drug intensification for conditioning regimen is also important.

[Detection of point mutation of K-ras gene codon 12 in biliary tract and ampullary carcinoma by modified two-step polymerase chain reaction].

The point mutation of K-ras gene at codon 12 was investigated in 11 cases of gall bladder carcinoma, 10 cases of extrahepatic bile duct carcinoma, 2 cases of intrahepatic bile duct carcinoma, and 4 cases of ampullary carcinoma by modified two-step polymerase chain reaction which employed paraffin embedded materials. The results revealed that there were point mutations in 6/11, 10/10, 2/2, and 4/4, respectively. Judging from the ratio of density of wild and mutant band, not all cancer cells in the tissue section contained the mutation. So it was suggested that the normal cells were initiated for the malignant transformation by ras gene mutations and then, selection might occur against cells containing ras mutations during progression of the tumor. Modified two-step polymerase chain reaction was markedly useful for detecting mutation even at low frequency among tumor cells.

[Second marrow transplantation following high dose busulfan, etoposide, and Ara-C after testicular relapse in a patient with AML].

Prognosis of second marrow transplantation after leukemia relapse is usually gloomy. We report a patient with AML who was successfully treated by the second marrow transplant following high dose busulfan, etoposide, and Ara-C for the testicular relapse after the first marrow transplantation. A 24-year-old man was diagnosed as having acute myeloid leukemia (AML) in September, 1988. In December of 1989 when he was in early relapse after his 2nd remission, he received the first allogeneic BMT from his HLA identical brother after high dose busulfan and cyclophosphamide conditioning. His posttransplant course was uneventful and graft versus host disease was not observed. Three months after BMT, he noticed swelling on right testicle. Leukemic cell infiltration was confirmed by aspiration cytology. The testicular relapse was followed by marrow relapse. After successful remission induction chemotherapy, he received 17.5 Gy testicular irradiation and second marrow transplantation using high dose busulfan, etoposide, and Ara-C conditioning. Although his posttransplant period was complicated by severe mucositis, high fever and bronchopneumonia, hematologic recovery was obtained by 3 weeks after the second transplant. He is now continuing in complete remission 18 months after the second BMT. This case report suggests that the combination of high dose busulfan, etoposide, and Ara-C could be a choice as a conditioning regimen for resistant AML relapsing after BMT.