Biomedical subjects
Publications and source records attributed to Hiroto Narimatsu.
This case highlights the importance of genetic evaluation during treatment in young patients with advanced ovarian cancer. Lynch syndrome caused by a germline MSH6 pathogenic variant was diagnosed during first-line maintenance therapy, and pembrolizumab achieved a durable response in recurrent disease.
We conducted a pilot study to evaluate the feasibility of reduced-intensity cord blood transplantation (RI-CBT) using a non-total body irradiation (TBI) regimen in adult patients with advanced hematologic malignancies. Seventeen patients with a median age of 58 years (range, 38-74) underwent RI-CBT at Tsukuba Memorial Hospital between April 2004 and November 2005. Preparative regimens were fludarabine 30 mg/m(2) for 6 days, and busulfan 4 mg/kg for 2 days. Tacrolimus was used for prophylaxis of graft-vs-host disease (GVHD). Median numbers of infused total nucleated were 2.6 x 10(7)/kg (range, 2.0-3.3). HLA disparity was found in 2/6 antigens (n=16) and 1/6 antigens (n=1). Underlying diseases progressed despite preparative regimens in four patients. Of the remaining 13 patients, nine patients achieved engraftment at a median of day 18 (range, 17-28). Six of the nine patients with engraftment achieved complete donor-type chimerism by day 100. Six patients were alive in remission at median follow-up of 13.1 months (range, 1.0-19.0). This study demonstrated the feasibility of RI-CBT using a non-TBI regimen in adults. When disease progression is controlled by the preparative regimen, RI-CBT carries a clinically significant graft-vs-tumor effect. Further studies are required to identify patients who benefit from this regimen.
Bortezomib is a novel proteasome inhibitor with significant antimyeloma activity. Its frequent adverse effects are manageable, including gastrointestinal symptoms, peripheral neuropathy, and thrombocytopenia. Severe lung toxicity has not previously been reported. Between June 2004 and September 2005, 13 Japanese patients with multiple myeloma were treated with bortezomib in Toranomon Hospital, Juntendo University School of Medicine, and Jichi Medical School. Four of them developed severe pulmonary complications, and 2 died of respiratory failure without progression of underlying disease. To our knowledge, this is the first report on life-threatening pulmonary adverse effects after bortezomib therapy. Previous clinical studies on bortezomib, mostly in the United States and Europe, have shown low incidences of pulmonary adverse effects. Our study suggests that bortezomib can cause serious lung injury, and that its incidence might vary among different ethnicities. Clinicians need to be alert to the possibility.
We reviewed the medical records of 123 adult reduced-intensity cord blood transplantation (RI-CBT) recipients to investigate the clinical features of graft failure after RI-CBT. Nine (7.3%) had graft failure, and were classified as graft rejection rather than primary graft failure; they showed peripheral cytopenia with complete loss of donor-type haematopoiesis, implying destruction of donor cells by immunological mechanisms rather than poor graft function. Three of them died of bacterial or fungal infection during neutropenia. Two recovered autologous haematopoiesis. The remaining four patients underwent a second RI-CBT and developed severe regimen-related toxicities. One died of pneumonia on day 8, and the other three achieved engraftment. Two of them died of transplant-related mortality, and the other survived without disease progression for 9.0 months after the second RI-CBT. In total, seven of the nine patients with graft failure died. The median survival of those with graft failure was 3.8 months (range, 0.9-15.4). Graft failure is a serious complication of RI-CBT. As host T cells cannot completely be eliminated by reduced-intensity preparative regimens, we need to be aware of the difficulty in differentiating graft rejection from other causes of graft failure following RI-CBT. Further studies are warranted to establish optimal diagnostic and treatment strategies.
Bloodstream infection (BSI) is a significant problem after cord blood transplantation (CBT). However, little information has been reported on BSI after reduced-intensity CBT (RI-CBT). We retrospectively reviewed the medical records of 102 patients. The median age of the patients was 55 years (range, 17-79 years). Preparative regimens comprised fludarabine 125 to 150 mg/m 2 , melphalan 80 to 140 mg/m 2 , or busulfan 8 mg/kg and total body irradiation 2 to 8 Gy. Prophylaxis against graft-versus-host disease comprised cyclosporin or tacrolimus. BSI developed within 100 days of RI-CBT in 32 patients. The cumulative incidence of BSI was 25% at day 30 and 32% at day 100. The median onset was day 15 (range, 1-98 days). Causative organisms included Pseudomonas aeruginosa (n = 12), Staphylococcus epidermidis (n = 11), Staphylococcus aureus (n = 6), Enterococcus faecium (n = 4), Enterococcus faecalis (n = 4), Stenotrophomonas maltophilia (n = 4), and others (n = 7). Of the 32 patients with BSI, 25 (84%) died within 100 days after RI-CBT. BSI was the direct cause of death in 8 patients (25%). Univariate analysis failed to identify any significant risk factors. BSI clearly represents a significant and fatal complication after RI-CBT. Further studies are warranted to determine clinical characteristics, identify patients at high risk of BSI, and establish therapeutic strategies.
We report the results of reduced-intensity unrelated cord blood transplantation (RI-UCBT) in patients with advanced malignant lymphoma. Twenty patients (median age, 46.5 years; range, 27-66 years) underwent RI-UCBT with a preparative regimen consisting of fludarabine 125 mg/m2 , melphalan 80 mg/m 2 , and 4 Gy of total body irradiation. The median infused total cell dose was 2.75 x 10(7)/kg (range, 2.3-3.4 x 10(7)/kg). Graft-versus-host disease (GVHD) prophylaxis was composed of cyclosporine or tacrolimus alone. Fifteen patients achieved primary neutrophil engraftment after a median of 20 days. Eight patients developed grade II to IV acute GVHD, and 2 developed chronic GVHD. Of the 16 patients with evaluable disease, 10 achieved a complete response. Primary disease recurred in 1 patient, and transplant-related mortality within 100 days occurred in 8 of 20 patients. The estimated 1-year probability of progression-free survival was 50%. These data suggest that RI-UCBT is a feasible option for patients with refractory lymphoma who lack an HLA-matched donor.
The Asian variant of intravascular lymphoma (AIVL) is characterized by hemophagocytic syndrome, pancytopenia and hepatosplenomegaly but usually lacks any neurological abnormality and skin lesions, which are typical features of classical intravascular lymphoma (IVL). An ante-mortem diagnosis of AIVL is difficult due to the absence of visible lymphoma lesions and unspecific clinical manifestations. A definite diagnosis relies on the presence of neoplastic B cells in the lumina of small vessels. Paraffin block samples of aspirated bone marrow clots were obtained from 4 patients with clinically suspected IVL and subjected to immunohistopathological analysis. All samples exhibited CD 20+ or CD 79a+ lymphoma cells proliferating intravascularly as well as erythrocytic hemophagocytosis. The distribution of neoplastic cells in the structure of the bone marrow allowed IVL to be distinguished from bone marrow invasions due to other types of lymphoma. We demonstrated the successful establishment of a definite ante-mortem diagnosis of AIVL in 3 of 4 patients by the rapid and simple method of using aspirated bone marrow samples.
Unmanipulated hematopoietic stem cell transplantation from haploidentical family donors is frequently associated with graft failure and severe graft-versus-host disease (GVHD). We employed a myeloablative conditioning regimen consisting of 125 mg/m2 of fludarabine, 140 mg/m2 of melphalan and TBI of 10 to 12 Gy for three patients. The donor in each case was a haploidentical two-loci HLA mismatch mother or son. Engraftment failure was observed in one patient. In the other two patients, engraftment was confirmed within 15 days after transplantation. Acute and chronic GVHD was observed, but was controllable in both cases. HLA mismatched transplantation based on feto-maternal tolerance may provide an alternative option for patients who do not have HLA-matched donors.
Explore the source record for details and available documents.
An 80-year-old woman was diagnosed with primary cutaneous B cell lymphoma. She had multifocal cutaneous tumors, but no nodal lymphadenopathy or bone marrow involvement. Histopathological examination of a biopsy specimen showed diffuse large B cell lymphoma without a bcl-2 expression. Complete resolution of hypercalcemia and disappearance of tumors were achieved with CHOP therapy, but a rapidly progressive skin lesion was observed soon after the completion of the therapy. The clinical manifestation of primary cutaneous diffuse large B cell lymphoma is diverse and the treatment strategy is not entirely clarified. This case represents another example of this rare lymphoma.
A 57-year-old woman with acute lymphoblastic leukemia (ALL) developed an antibiotics-resistant fever after remission induction therapy. Chest X-ray and computed tomography scan revealed multiple consolidations and cavities. Successively, numerous subcutaneous nodules and a thyroid mass emerged. Aspergillus flavus (A. flavus) was cultured from both sites. Despite the patient's granulocyte recovery, the fever persisted and multiorgan function deteriorated rapidly. However, she was successfully treated with intensive supportive therapy including continuous hemodialysis and filtration. Prolonged use of amphoterin B and itraconazole failed to cure her aspergillosis, but the illness remained indolent thereafter.