Nationwide survey of allogeneic peripheral blood stem cell transplantation from related donors in Japan: current trends and issues

In December 1997, we conducted a nationwide survey of cases of primary allogeneic peripheral blood stem cell transplantation (allo-PBSCT) performed in Japan between December 1994 and November 1997 Data was collected on 103 patients with hematologic malignancies, aplastic anemia, or solid tumors. Eighty-seven patients received transplants from HLA-identical siblings, and 16 from HLA-mismatched related donors. Granulocyte-colony stimulating factor (G-CSF) mobilized peripheral blood stem cells (PBSC) were collected from donors by 1 to 3 aphereses. Apheresis products contained a median 5.4 (1.0-30.4) x 10(6) CD34 + cells/kg. Most patients were given cyclosporine and methotrexate for graft-versus-host disease (GVHD) prophylaxis. Median days to ANC > 500/microliter and platelets > 50,000/microliter were 13 (7-49) and 16 (10-94), respectively. Grade II-IV acute GVHD developed in 37/99 (37.4%) and chronic GVHD in 59/86 (68.6%) patients. The incidence of treatment-related mortality within 100 days after transplant was 16.1%. Fifty-five patients (59.6%) were alive after a median follow-up of 794 days. More patients and longer follow-up periods will be required to assess the efficacy of allo-PBSCT and evaluate graft-versus-leukemia effect along with the incidence of acute and chronic GVHD.     

Bone marrow transplantation in niemann-pick mice

Journal of Inherited Metabolic Disease -     

A case of pulmonary actinomycosis with recurrent hemoptysis diagnosed after right upper lobectomy]

The patient was a 58-year-old man who had been admitted in 1995 because of hemoptysis. Chest CT scans showed air-space consolidation with dilated bronchi and calcification in the right S3. He received a diagnosis of bronchiectasis with old tuberculosis. Bronchial arteriography showed arterialization in the right S3, and bronchial artery embolization was performed. But in 1996 hemoptysis reappeared. He was readmitted in May 1999 because of recurrent hemoptysis. Bronchial arteriography showed recurrence of arterialization in the same area, and chest CT scans showed growth of the mass shadow. Right upper lobectomy was performed, and the microscopic findings of the resected specimen showed sulfur granules in the dilated bronchus. We concluded that pulmonary actinomycosis should be considered in the differential diagnosis of abnormal chest shadows.     

Mouse model of airway remodeling: strain differences

We found that continuous eosinophilic inflammation after repeated antigen instillation into the nose was observed only in A/J mice, not in three other strains. Histologic analysis of tissues from A/J mice revealed features typical of airway remodeling, i.e., airway wall thickening and increased collagen depositions were observed after 12 weeks' antigen exposure. Persistent airway hyperresponsiveness (AHR) was observed in chronically antigen-exposed A/J mice. Eosinophilic inflammation, collagen deposition, and airway wall thickening were all less marked in BALB/c mice than in A/J mice, and no AHR was observed in the former strain. In C57BL/6 and C3H/HeJ mice, eosinophilic inflammation, airway wall thickening, and AHR were not observed at all, although slightly increased collagen deposition was observed. Thus, we found that these changes were strain-dependent. On the other hand, in A/J mice inhalational antigen challenge after ovalbumin/alum immunization led only to a transient increase in eosinophils and to less airway wall thickening, indicating the importance of the protocol used. Use of A/J mice and giving antigen by instillation via the nose is to be recommended for studies of the mechanisms underlying asthma. In particular, useful qualitative and quantitative information relating to the structural and histologic changes in the lungs may be obtainable using this model.     

Risk of neutropenic fever and early infectious complications after autologous peripheral blood stem cell transplantation for malignant diseases

Autologous peripheral blood stem cell transplantation (auto-PBSCT) has facilitated high-dose chemotherapy for the treatment of various types of malignancy, but the factors affecting the treatment outcome have not been well defined. We evaluated patients who underwent auto-PBSCT (46 patients with hematological malignancies and 39 with solid tumors) to elucidate the risks of background factors, including age, in association with infectious complications. In contrast to former reports, faster engraftment did not influence the incidence of documented infection or neutropenic fever, whereas high age (age > or = 50 years old) and delayed platelet recovery (> or = 18 days) were demonstrated to be positively involved. The odds ratio (OR) for documented infection in elderly patients was 4.94 (95% confidence interval, 1.22-15.8). Another risk factor of infection was the HD-ICE regimen (ifosfamide, carboplatin, etoposide) given to patients with solid tumors (OR, 8.00; 95% confidence interval, 1.61-39.7). In conclusion, we found that elderly patients and patients on the HD-ICE regimen have a higher risk of infectious complications even after auto-PBSCT. Although the clinical indications for auto-PBSCT can be extended to elderly patients, thorough precautions should be taken against infectious complications during the pre-engraftment phase.     

Ocular Manifestation of Acute Graft-Versus-Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation

A 26-year-old woman with acute myeloid leukemia underwent allogeneic peripheral blood stem cell transplantation from an HLA-identical brother. Eighteen days after transplantation, the patient developed grade II acute graft-versus-host disease (GVHD) and was treated with corticosteroids. On day 38, the patient complained of eye pain and lacrimation. A slitlamp examination revealed corneal ulcers and pseudomembranous formation in both eyes. Histologic and immunohistochemical examinations of the pseudomembrane disclosed an infiltrate dominated by T cells. A cytogenetic study of the pseudomembrane by fluorescence in situ hybridization identified a Y chromosome in the infiltrated mononuclear cells. Surveillance cultures from conjunctival swabs were negative. Thus, we diagnosed these ocular manifestations as an ocular involvement of acute GVHD.     

A multicenter early phase II study of high-dose chemotherapy with autologous peripheral blood stem cell transplantation for treatment of intermediate-grade non-Hodgkin's lymphoma. Japan Blood Cell Transplantation Study Group

We conducted a multicenter early phase II study to evaluate the feasibility and therapeutic efficacy of high-dose chemotherapy supported by autologous peripheral blood stem cell transplantation (auto-PBSCT) for the treatment of intermediate grade non-Hodgkin's lymphoma (IG-NHL). High-dose etoposide or cyclophosphamide followed by G-CSF was used for PBSC mobilization, and a sufficient number of CD34+ cells (> 1 x 10(6)/kg) were collected. Out of 81 enrolled patients, 50 received high-dose chemotherapy with auto-PBSCT; Hematologic recovery after transplantation was rapid. The incidence of grade III/IV toxicity (Bearman) was about 6%; treatment-related mortality was 6% (3/50). The Disease-free survival rate for the patients in complete remission who received high-dose chemotherapy with auto-PBSCT was better than that for the patients who were treated with conventional chemotherapy (57% vs 35%). These preliminary results indicated that high-dose chemotherapy with auto-PBSCT is feasible and effective. A prospective randomized phase III clinical trial will be required to assess the efficacy of high-dose chemotherapy with auto-PBSCT as a post-remission therapy for IG-NHL.     

A questionnaire survey on the theory of postoperative infection prophylaxis in gynecology]

A questionnaire survey on the theory of postoperative infection prophylaxis was conducted to obtain the consensus on perioperative antimicrobial use among gynecologists in Japan in the period from April to July 2000. Fifty-six of the 83 gynecologists replied, and the following consensus was obtained. An antimicrobial prophylaxis (AMP) agent should be chosen based on their efficacy against the pathogens expected to be contaminants, such as Staphylococcus spp., Escherichia coli and Bacteroides fragilis group. Use an AMP agent that archives a bactericidal concentrations in both the serum and operating site. Use an AMP agent that has little unfavourable side effects. The newer agents should be considered as a therapeutics for postoperative infections. The therapeutic antimicrobial agents having no cross-resistance to the AMP agents should be used, if postoperative infection is suspected or developed. The most commonly used agent for clean operations are cefazolin (CEZ), followed by cefotiam (CTM) and cefmetazole (CMZ). The most commonly used agent for clean-contaminated operations where low grade level of bacterial invasion expected is CTM, followed by CEZ and CMZ, where as operations where mild grade level of bacterial invasion expected is flomxef (FMOX), followed by CTM and other cephalosporins.     

Successful engraftment of allogeneic peripheral blood stem cell transplant after nonmyeloablative preparative regimen with cytarabine and cyclophosphamide: report of 2 cases

We report our experience with allogeneic peripheral blood stem cell transplantation (allo-PBSCT) following a nonmyeloablative conditioning regimen consisting of cytarabine (8 g/m2) and cyclophosphamide (120 mg/kg) in the treatment of 2 patients aged 50 and 55 years with refractory chronic myelomonocytic leukemia and chronic myeloid leukemia in accelerated phase, respectively. Our nonmyeloablative regimen was well tolerated by older patients at high risk of regimen-related toxicity by the conventional conditioning regimen but was immunosuppressive enough to achieve mixed chimerism. After allo-PBSCT, we monitored chimerism in these patients by fluorescence in situ hybridization using X- and Y-specific probes and polymerase chain reaction-based analysis of a variable number of tandem repeats. We found that full chimerism and graft-versus-leukemia (GVL) effects could be induced in these patients by donor lymphocyte infusions and withdrawal of posttransplantation immunosuppressive therapy. Our observations suggest that a nonmyeloablative conditioning regimen can establish mixed chimerism and that donor lymphocyte infusion may induce GVL effects in older patients at high risk of regimen-related toxicity.