Cefepime or carbapenem treatment for febrile neutropenia as a single agent is as effective as a combination of 4th-generation cephalosporin + aminoglycosides: comparative study.

1998, a consensus meeting was held in Miyazaki, Japan, to develop an approach to management of febrile neutropenia (FN). The K-HOT study group decided to examine whether this proposal was applicable to clinical practice in a multicenter study. Patients who developed fever with neutrophil counts <1,000/microL were randomized to receive either a single antibiotic, cefepime or one of the carbapenems, or a combination of cefepime and an aminoglycoside. Patients who became afebrile within the first 3 days were continued on the same treatment. Patients who remained febrile were switched to a combination regimen if they were randomized to receive a single agent, and patients on combination medication were changed from cefepime to another cephalosporin. A total of 165 patients were entered into the trial. One hundred fifty-three patients were evaluable for response. The average age was 52 years, and 70% of the patients had acute leukemia. Severe neutropenia, defined as <100/microL at the time of FN, was seen in 62% of the patients on entry and during the course of treatment 71% of patients experienced neutrophil counts of <100/microL. Microbiologically documented infection was seen in 6.5% for monotherapy, and 10.5% for a combination treatment, and fever of unknown origin occurred in 75.3% and 59.2% of the patients in each regimen, respectively. Excellent to good response was seen in two-thirds of the patients in all treatment groups. Adverse events were minimal, and three early deaths were observed at days 9, 16, and 16 among patients treated with a single antibiotic and three in the combination regimen group at days 14, 15, and 20. These results indicate that cefepime or a carbapenem alone is as effective as a combination of cefepime and an aminoglycoside for treating FN.

A case of CD56+ cutaneous aleukaemic granulocytic sarcoma with myelodysplastic syndrome.

We describe a 70-year-old man with cutaneous granulocytic sarcoma who presented with numerous cutaneous nodules but without any leukaemic involvement of the peripheral blood. The tumour cells were positive for lysozyme, peroxidase, CD11a, CD11c, CD33 and HLA-DR, and weakly positive for CD4 and CD14, suggesting granulocytic differentiation. The bone marrow at admission showed dysplasia of the erythrocytic and granulocytic lineage and complex chromosomal abnormalities in association with an increase in monocytes. The patient was diagnosed as having granulocytic sarcoma of monocytic lineage with concomitant myelodysplastic syndrome. In this case, tumour cells also expressed the neural cell adhesion molecule (CD56), which has been suggested as a possible risk factor for developing granulocytic sarcoma in acute myelogenous leukaemia.

A case of multiple myeloma which developed into multiple extramedullary involvement in the terminal stage.

A 69-year-old man with a diagnosis of multiple IgG class myeloma received combination chemotherapy. He achieved a partial response with an undetected M spike. However, he demonstrated new lytic bone lesions and multiple extramedullary involvement 10 months after the initial presentation. Polymerase chain reaction (PCR) analysis using a framework 3 (Fr3) V-region primer clarified a discrete band in the extramedullary tumor, while it yielded 4 bands including the same size as the extramedullary tumor produced in the bone marrow sample obtained before the chemotherapy. These findings suggest that a resistant and non-secretory clone was selected by the combination chemotherapy.

Autologous peripheral blood stem cell transplantation for acute myelogenous leukemia.

The safety and efficacy of myeloablative therapy followed by autologous peripheral blood stem cell transplantation (ABSCT) for acute myelogenous leukemia (AML) were evaluated in 60 patients. Peripheral blood stem cells (PBSC) were collected during recovery after consolidation chemotherapy. High-dose chemotherapy consisting of busulfan (16 mg/kg), etoposide (40 mg/kg), and cytosine arabinoside (3 g/m2 x 4) (BEA regimen) was used for pretransplant conditioning in 13 patients. For the remaining 47 patients, granulocyte colony-stimulating factor (G-CSF) was administered concurrently with the BEA regimen during conditioning. Unpurged, cryopreserved PBSC containing a median number of 5.4 x 10(8) MNC/kg or 12 x 10(4) CFU-GM/kg were reinfused at transplantation. The median number of days to granulocytes exceeding 500/microl and last platelet transfusion were 15 (8-44) and 24 (0->180), respectively. The 3-year probabilities of disease-free survival (DFS) and relapse were 78.6 and 21.4% for patients transplanted in first remission, 29.6 and 64.4% for those in second or third remission, and 11.1 and 77.8% for those in relapse, respectively. There were no transplant-related deaths within 100 days of transplantation. Age, disease status at transplantation, and number of induction chemotherapies to first complete remission were risk factors affecting the outcome of ABSCT. These results of ABSCT for AML in first remission warrant a prospective study of ABSCT as post-remission therapy.

Increased incidence of cytomegalovirus (CMV) infection and CMV-associated disease after allogeneic bone marrow transplantation from unrelated donors. The Fukuoka Bone Marrow Transplantation Group.

Cytomegalovirus (CMV) infection and CMV-associated disease were monitored using the CMV antigenemia assay in 72 patients who received allogeneic bone marrow transplantation (BMT), and their incidences were compared between related and unrelated donor transplant patients. The incidence of CMV infection after BMT was significantly higher in patients who received transplants from HLA-matched unrelated donors than from HLA-matched sibling donors (87% vs 53%, P < 0.05). CMV-associated disease developed in 73% of unrelated and in 14% of sibling donor transplant patients (P < 0.01). The peak levels of CMV antigenemia were significantly higher in unrelated donors than in sibling donor transplant patients (16 vs 1 CMV antigen-positive cells per 50000 WBCs, P < 0.01). The median number of CMV antigen-positive cells on first detection was also significantly higher in unrelated donor transplant patients (15 vs 1, P < 0.01). The detection of CMV antigen-positive cells preceded the development of CMV-associated disease in 18% of unrelated donor transplant patients, suggesting a lower predictive value of CMV antigenemia for subsequent CMV-associated disease in unrelated donor BMT. Careful monitoring and further studies are needed for the early diagnosis and prevention of CMV-associated disease in unrelated donor BMT.

An autopsy case of B-cell lymphoma associated with macroglobulinemia (IgM-k).

While he was treated for macroglobulinemia showing symptoms, a 65-year-old man developed an enlargement of the left lateral cervical lymph node. Biopsy specimens of the cervical lymph node revealed large-cell non-Hodgkin's lymphoma. The lymphoma cells had rearrangement in the immunoglobulin heavy chain and kappa light chain genes. There was osteolysis involving right metatarsal bones. And, a tumor appeared on the upper hard palate in the terminal stage. Autopsy specimens showed infiltration of lymphoma cells into multiple organs. Production of monoclonal immunoglobulin M was detected only slightly and focally in the tumors. Plasmacytic differentiation as in Waldenström's macroglobulinemia was not seen in any organs except the tumor on the upper hard palate. From these findings, it is speculated that B-cell lymphoma might have developed in the course of macroglobulinemia.

Allogeneic peripheral blood stem cell transplantation for treatment of induction failure in a patient with Philadelphia chromosome-positive acute lymphoblastic leukemia.

We report a successful case of allogeneic peripheral blood stem cell transplantation (PBSCT) for the treatment of primary induction failure in acute lymphoblastic leukemia (ALL). The patient was a 46-year-old male with Ph-positive ALL and failed to achieve complete remission (CR). His HLA genotypically identical brother refused to donate bone marrow. Instead, PBSCs were collected by apheresis from the brother after administration of G-CSF at a dose of 10 micrograms/kg. For allogeneic PBSCT, the patient was conditioned with marrow ablative chemotherapy and received the PBSC harvest containing 7.8 x 10(4)/kg of CFU-GM, 1.8 x 10(6)/kg of CD34-positive cells and 2.7 x 10(8)/kg of T lymphocytes. After transplant, the neutrophil count exceeded 0.5 x 10(9)/l on day 16 and the platelet count exceeded 20 x 10(9)/l on day 22. CR was confirmed with tri-lineage engraftment in bone marrow samples on days 28 and 49; disappearance of the Ph-chromosome was documented. Sustained engraftment was also confirmed cytogenetically using a variable number of tandem repeat (VNTR) markers. Acute graft-vs.-host disease did not develop with conventional prophylaxis of methotrexate and cyclosporine. However, on day 85 the patient developed leukemia relapse and died on day 97. This clinical trial suggests that allogeneic PBSCT may be an alternative to allogeneic bone marrow transplantation in some limited situations.

Recombinant human glycosylated granulocyte colony-stimulating factor (rhG-CSF)-combined regimen for allogeneic bone marrow transplantation in refractory acute myeloid leukemia.

Recombinant human glycosylated G-CSF (rhG-CSF) may stimulate proliferation of myeloid leukemia cells and thereby increase their susceptibility to anti-cancer agents. By in vitro colony assay, the rhG-CSF-responsive NFS-60 leukemic cell clones are more effectively killed by Ara C in the presence of rhG-CSF than in the absence of rhG-CSF, while the killing of the rhG-CSF-unresponsive HL-60 cell clones is unaffected by rhG-CSF. Leukemia cell colony forming units (L-CFU) derived from most AML patients demonstrate similar results to those of the NFS-60 cell clone when treated in vitro. Encouraged by these in vitro results, we used rhG-CSF as a component of a conditioning regimen for 15 relapsed AML patients who were receiving allogeneic BMT. The patients were conditioned with total body irradiation (TBI) and high-dose Ara C. rhG-CSF was infused continuously at a dose of 5 micrograms/kg/day from 24 h before the beginning of TBI to the end of Ara C therapy. Proliferation of the leukemia cells in vivo in response to rhG-CSF was confirmed in 7 of 14 patients tested and the combined use of rhG-CSF had no additional adverse effects. After BMT, four patients died of non-leukemic causes and three patients had leukemic relapse: the other eight patients have remained disease-free for 200-1600 (median 417) days. The actuarial probabilities of relapse and disease-free survival (DFS) at 4.4 years after BMT were 43.2% and 41.7%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

[Acute renal failure associated with acute type A hepatitis with a mild liver damage].

Acute renal failure associated with acute type A hepatitis was successfully treated with hemodialysis. Though acute renal failure is usually associated with severe liver damage of end stage cirrhosis or fulminant hepatitis, liver damage of our case was only slight. The etiology of the renal failure is discussed.

Sonographic diagnosis of venocclusive disease of the liver and danazol therapy for autoimmune thrombocytopenia in an autologous marrow transplant patient.

A 16-Year-old boy with lymphoblastic lymphoma underwent an autologous bone marrow transplantation (ABMT) after conditioning with high-dose busulfan and cyclophosphamide. On day 39 post-transplant, right upper quadrant pain occurred with an increase in the size of the liver. Liver function tests showed a subsequent deterioration. Ultrasonographic studies of the abdomen disclosed hepatosplenomegaly, ascites, thickening of the gall bladder wall and a failure to visualize the major hepatic veins. The venocclusive disease of the liver (VOD) diagnosis was confirmed from these findings. Ultrasonographic monitoring reflected the disease status well and demonstrated a complete recovery from the VOD. We emphasize, thus, that abdominal ultrasonography can be applied easily, being a non-invasive procedure, and is useful in diagnosing VOD. Furthermore, the procedure can be repeated serially for evaluating the severity of VOD. Although engraftment was confirmed with granulocytes exceeding 500/microliters, platelet recovery was delayed; the megakaryocytes had not decreased in bone marrow aspirates and platelet-associated IgG was significantly elevated. Since autoimmune thrombocytopenia was highly suspected, to prevent immunosuppression danazol was given as an immune modulator instead of prednisolone, and a complete recovery was obtained. Accordingly, danazol can be used as an alternative to prednisolone for the treatment of autoimmune thrombocytopenia after bone marrow transplantation.