A nationwide survey on central nervous system multiple myeloma in Japan: analysis of prognostic and treatment factors that impact survival.

This nationwide multicentre retrospective study was performed to analyze clinical features that predict the prognosis of central nervous system invasion in multiple myeloma (CNS-MM, approximately 1% of MM). Overall, of the 77 adult patients with CNS-MM identified between 2005 and 2016, those diagnosed at MM diagnosis (n = 3) had longer overall survival (OS) than those diagnosed at relapse (n = 74; median: 48·5 vs 2·7 months). Therefore, we compared the relapsed MM with CNS-MM in patients with any treatment (n = 60). Multivariate analyses revealed that lenalidomide treatment [hazard ratio (HR) 0·27, P = 0·003], intrathecal chemotherapy (IT; HR 0·54, P = 0·05), and radiation therapy (RTx; HR 0·33, P < 0·001) for CNS-MM had a positive effect on longer OS. These factors were used to develop a scoring system combining the number of treatments with lenalidomide, IT, and RTx (0, 1, 2, 3). The OS of CNS-MM patients was stratified based on these factors, with a median OS of 1·1, 4·5, and 7·5 months for patients with zero, one, two to three favourable features, respectively (0 vs 1, P = 0·0002; 1 vs 2-3, P = 0·08). Multimodal treatment including lenalidomide in addition to conventional IT and RTx can improve OS.

Reassessment of clinical implication of pretransplant surgical procedures for pulmonary invasive fungal lesions.

Dealing with the recent series of allogeneic hematopoietic stem cell transplantation (allo-SCT) performed this decade, we reassessed the clinical impact of pretransplant surgical procedures (SP) for pulmonary lesions of invasive fungal disease (IFD) on subsequent transplant outcome. We focused on the clinical outcomes of seven patients with pulmonary IFD who underwent segmentectomy (n = 4), lobectomy (n = 2) or abscess incision with drainage only (n = 1), and compared results to those of 21 patients carrying pulmonary IFD who never underwent invasive SP before allo-SCT. The rate of exacerbation of pulmonary lesions by 180 days after allo-SCT did not differ significantly between groups (32.2% vs 42.9%, P = 0.69). Moreover, no significant differences in non-relapse mortality (46.4% vs 42.3%, P = 0.93) or overall survival (53.6% vs 30.9%, P = 0.45) at 1 year were evident between groups. These results indicate that pretransplant SP for pulmonary lesions might have no survival benefit under the current antifungal prophylaxis or treatment modality.

Extramedullary Gastric Relapse at the Time of Bone Marrow Relapse of Acute Lymphoblastic Leukemia after Allogeneic Bone Marrow Transplantation.

Extramedullary relapse (EMR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is relatively rare. The most commonly reported sites in acute lymphoblastic leukemia (ALL) patients after allo-HSCT are soft tissue and the central nervous system, and the gastrointestinal system is an uncommon site. We herein report a unique case with massive hematemesis resulting from gastrointestinal relapse of ALL after allo-HSCT. Upper gastrointestinal endoscopy showed bleeding from a 1.5-cm submucosal tumorous lesion with central ulceration on the anterior wall of the stomach. At the same time, computed tomography revealed extramedullary relapse at the breast and bilateral adrenal glands.

Predictive implications of albumin and C-reactive protein for progression to pneumonia and poor prognosis in Stenotrophomonas maltophilia bacteremia following allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Stenotrophomonas maltophilia (S. maltophilia) bacteremia causes significant morbidity and mortality in immunocompromised hosts. However, incidence and risk factors for mortality in S. maltophilia bacteremia following allogeneic hematopoietic stem cell transplantation (allo-HSCT) remain controversial. The primary aim of this study is to clarify factors associated with poor prognosis of allo-HSCT recipients with S. maltophilia bacteremia. METHODS: From January 2005 to December 2014, patients with hematological diseases and S. maltophilia bacteremia at a single transplantation center in Japan were examined for incidence and 90-day mortality. Prognostic factors associated with 90-day mortality among allo-HSCT recipients were analyzed by log-rank test, and significant variables in the univariate analysis were included in the multivariate Cox proportional-hazards regression model. RESULTS: A total of 65 patients, including 47 patients undergoing allo-HSCT, developed S. maltophilia bacteremia. The incidence of S. maltophilia bacteremia was significantly higher in allo-HSCT recipients compared to patients not receiving allo-HSCT (6.53 vs. 0.36 per 100 admissions, respectively; p < 0.01). The overall 90-day mortality in allo-HSCT recipients was 43%. Independent risk factors for 90-day mortality were low serum albumin (<3.0 g/dl) (HR = 10.86; 95% CI, 3.27-36.12) and high serum C-reactive protein (CRP) (≥10.0 mg/dl) (HR = 3.28; 95% CI, 1.00-10.72). Among 9 patients with both high CRP and low albumin, 5 had pneumonia at the onset of bacteremia and the remaining 4 patients developed pneumonia in a median of 3 days (range, 1 to 8 days) even under effective treatment. All 9 patients eventually died in a median of 2 days (range, 2 to 32 days). The probabilities of developing pneumonia in patients with or without high CRP and low albumin levels were 100% (9/9) and 10.5% (4/38), respectively (p < 0.01). CONCLUSIONS: Allo-HSCT recipients had higher rates of S. maltophilia bacteremia than did patients not receiving allo-HSCT. High serum CRP and low serum albumin at the onset of bacteremia are predictive of disease progression to pneumonia and poor prognosis.

Clinical impact of pre-transplant gut microbial diversity on outcomes of allogeneic hematopoietic stem cell transplantation.

Post-transplant microbial diversity in the gastrointestinal tract is closely associated with clinical outcomes following allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, little is known about the impact of the fecal microbiota before allo-HSCT. We analyzed fecal samples approximately 2 weeks before conditioning among 107 allo-HSCT recipients between 2013 and 2015. Microbial analysis was performed using 16S rRNA gene sequencing. Operational taxonomic unit-based microbial diversity was estimated by calculating the Shannon index. Patients were classified into three groups based on the diversity index: low (<2), intermediate (2, 3), and high (>3) diversity (18 (16.8%), 48 (44.9%), and 41 (38.3%) patients, respectively). There were no significant differences in the 20-month overall survival, cumulative incidence of relapse, and non-relapse mortality among three groups. The cumulative incidence of grade II to IV acute graft-versus-host disease (aGVHD) was similar among the three groups (low 55.6%; intermediate 35.4%; high 48.8%, p = 0.339, at day 100). Furthermore, we found no differences in the cumulative incidence of grade II to IV acute gastrointestinal GVHD among the three groups (low 38.9%; intermediate 21.3%; high 24.4%, p = 0.778, at day 100). Regarding the composition of microbiota before allo-HSCT, aGVHD patients showed a significantly higher abundance of phylum Firmicutes (p < 0.01) and a lower tendency for Bacteroidetes (p = 0.106) than non-aGVHD patients. Maintenance of Bacteroidetes throughout allo-HSCT may be a strategy to prevent aGVHD.

Outcomes of Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia Patients with Abnormalities of the Short Arm of Chromosome 17.

We retrospectively analyzed a Japanese nationwide database to elucidate the impact of abnormalities in the short arm of chromosome 17 (abnl[17p]) on the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloid leukemia. Of 10,923 patients, 262 (2.4%) had abnl(17p), 235 of whom were classified into the poor cytogenetic risk group according to the National Comprehensive Cancer Network criteria. The median follow-up period was 1425 days. In abnl(17p) versus non-abnl(17p) patients of poor cytogenetic risk group, overall survival (OS), disease-free survival, cumulative incidence of disease relapse, and nonrelapse mortality rates at 5 years after allo-HSCT were 9.2% versus 27.4%, 7.8% versus 25.0%, 66.6% versus 49.4%, and 25.6% versus 25.6%, respectively. In contrast to the other types of abnl(17p), isochromosome 17q rarely encompassed the poor cytogenetic risk traits and did not adversely affect OS. Among the abnl(17p) patients, male sex, nonremission disease status at transplantation, and poor cytogenetic risk group were significantly associated with shorter OS. In conclusion, the presence of an abnl(17p) negatively affects allo-HSCT outcomes, which are influenced by the type of abnormality. Prompt initiation of allo-HSCT during complete remission may improve outcomes.

Comparison of transplant outcomes and economic costs between biosimilar and originator filgrastim in allogeneic hematopoietic stem cell transplantation.

From January 2012 to September 2015, 49 patients received biosimilar filgrastim (BF) after allogeneic bone marrow transplantation (BMT, n = 31) or peripheral stem cell transplantation (PBSCT, n = 18) in our institution. To evaluate the clinical impact of BF on transplant outcomes of these patients, we compared hematological recovery, overall survival (OS), disease-free survival (DFS), transplantation-related mortality (TRM), cumulative incidence of relapse (CIR), and acute and chronic graft-versus-host disease (GVHD) with those of control patients who received originator filgrastim (OF) after BMT (n = 31) or PBSCT (n = 18). All cases were randomly selected from a clinical database in our institution. In both the BMT and PBSCT settings, neutrophil recovery (17 vs. 19 days in BMT; 13 vs. 15 days in PBSCT) and platelet recovery (27 vs. 31 days in BMT; 17 vs. 28 days in PBSCT) were essentially the same between BF and OF. They were also comparable in terms of OS, DFS, TRM, CIR, and the incidence of acute GVHD and chronic GVHD. On multivariate analysis, the use of BF in both BMT and PBSCT was not a significant factor for adverse transplant outcomes. Although BF significantly reduced filgrastim costs in both BMT and PBSCT, total hospitalization costs were not significantly different between BF and OF.