玉置 雅治

Allogeneic hematopoietic stem cell transplantation from a female donor to a male recipient (female-to-male allo-HCT) is a well-established risk factor for chronic graft-versus-host disease (GVHD) and non-relapse mortality (NRM). The inferior outcomes of female-to-male allo-HCT are considered to be due to allo-immunity against H-Y antigens. However, the influence of minor histocompatibility antigens in haplo-identical allo-HCT remains to be elucidated. We investigated the impact of female-to-male allo-HCT according to the haplo-HCT subtype. In the post-transplant cyclophosphamide (PTCY) cohort (n = 660), a female-to-male sex-mismatch was significantly associated with a decreased risk of relapse (HR: 0.70 [95% CI: 0.49-0.99], P = 0.045), but not with overall survival (OS) or NRM (HR: OS 0.89 [95% CI: 0.68-1.16], P = 0.40; NRM 0.98 [95% CI: 0.68-1.41], P = 0.90). On the other hand, in the non-PTCY cohort (n = 219), a female-to-male sex-mismatch was associated with inferior risks of OS and NRM, but was not associated with relapse. These results suggested that the survival impact of the haplo-HCT subtype differed according to the presence of a sex-mismatch. PTCY might be feasible for overcoming the inferiority of female-to-male allo-HCT and might preserve a GVL effect against H-Y antigens.

Chronic graft-versus-host disease (GVHD) is 1 of the major complications after allogeneic hematopoietic cell transplantation (allo-HCT). Although various risk factors for chronic GVHD have been reported, limited data are available regarding the impact of acute GVHD on chronic GVHD. We examined the association between acute and chronic GVHD using a Japanese registry data set. The landmark point was set at day 100 after allo-HCT, and patients who died or relapsed before the landmark point were excluded. In total, 14 618 and 6135 patients who underwent allo-HCT with bone marrow or peripheral blood (BM/PB) and with umbilical cord blood (UCB), respectively, were analyzed. In the BM/PB cohort, the risk for chronic GVHD that requires systemic steroids increased with each increase in acute GVHD grade from 0 to 2 (grade 0 vs 1 [hazard ratio (HR), 1.32; 95% confidence interval (CI), 1.19-1.46; P < .001]; grade 1 vs 2 [HR, 1.41; 95% CI, 1.28-1.56; P < .001]), but the risk was similar between acute GVHD grade 2 and grade 3 to 4 (HR, 1.02; 95% CI, 0.91-1.15; P = 1.0). These findings were confirmed in the UCB cohort. We further observed that the risk for severe chronic GVHD increased with each increment in the grade of acute GVHD, even between acute GVHD grade 2 and grade 3 to (grade 2 vs 3-4: HR, 1.70; 95% CI, 1.12-2.58; P = .025). In conclusion, the preceding profiles of acute GVHD should help to stratify the risk for chronic GVHD and its severity, which might be useful for the development of risk-adopted preemptive strategies for chronic GVHD.

BACKGROUND AIMS: Pre-transplant lung dysfunction is known to be a risk factor for non-relapse mortality (NRM) after allogeneic hematopoietic cell transplantation (allo-HCT). It is unclear which cell source gives better outcomes for patients with pulmonary dysfunction. METHODS: We analyzed 3289 adult patients with standard-risk disease who had received HLA-matched allo-HCT, and compared outcomes between those who received peripheral blood stem cell (PBSC) vs. bone marrow (BM) in two cohorts based on the presence of a lung score by the Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI): the Lung-scored (LS) and non-LS cohorts. RESULTS: In the LS cohort, the 2-year overall survival (OS) in the BM group tended to be higher than that in the PBSC group (72.4% vs. 61.4%; P = 0.044). In the non-LS cohort, there was no significant difference between the two groups (71.7% vs. 73.2%; P = 0.13). Multivariate analyses confirmed that PBSC was significantly associated with inferior OS in the LS cohort (hazard ratio [HR], 1.66; 95% CI, 1.09-2.54; P = 0.019). On the other hand, the cell source did not affect OS in the non-LS cohort (HR, 0.92; 95% CI, 0.76-1.12; P = 0.41). We found that PBSC was associated with an increased risk of NRM in the LS cohort (HR, 2.17; 95% CI, 1.16-4.05; P = 0.016), while the cell source did not significantly affect NRM in the non-LS cohort. PBSC was not identified as a risk factor for relapse in either cohort. CONCLUSIONS: Our results suggest that BM might be beneficial for recipients with lung dysfunction in HLA-matched allo-HCT.

BACKGROUND: Monitoring of HBV-DNA and HBV-DNA-guided preemptive therapy using nucleos(t)ide analogues (NAs) are recommended for preventing the development of hepatitis due to HBV reactivation after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in recipients with resolved HBV infection. However, little is known about the appropriate duration of NA treatment and the outcomes of NAs cessation on recurrence of HBV reactivation. OBJECTIVE: To clarify the consequences of NAs cessation in recipients with resolved HBV infection who experienced HBV reactivation following allo-HSCT. STUDY DESIGN: We retrospectively reviewed the clinical records of recipients with resolved HBV infection (HBsAg-negative, anti-HBc-positive) before allo-HSCT who had been diagnosed as having HBV reactivation (HBsAg-positive and/or HBV-DNA detectable) after allo-HSCT during the period from January 2010 to December 2020. RESULTS: A total of 72 patients from 16 institutes were registered (median age of the patients, 60 years; age range, 27-73 years; 42 males and 30 females). Initial HBV reactivation was observed on day 10 to day 3034 (median, 513 days) after allo-HSCT. Anti-HBs were lost in more than 80% of the patients at the time of HBV reactivation. All 72 patients received preemptive NAs and no fatal HBV reactivation-related hepatitis was observed. There was continuous detection of HBV-DNA without hepatitis in 5 patients during the follow-up period. Administration of NAs was discontinued in 24 (33%) of 72 patients by each physician's decision. Second HBV reactivation occurred in 11 (46%) of the 24 patients in whom administration of NAs was discontinued. Duration of NA treatment were not significantly different between patients with or without second HBV reactivation. The frequency of further HBV reactivation tended to be lower in patients with anti-HBs titer of more than 10 mIU/mL at the time of NA cessation. CONCLUSION: Multiple reactivation of HBV after NA discontinuation was common in patients with HBV reactivation who received allo-HSCT despite the long duration of NA. Careful monitoring of HBV-DNA is important even after the discontinuation of NA in the case with HBV reactivation after allo-HSCT because multiple reactivations could occur. Active immunization by HB vaccine might be effective for suppressing further HBV reactivation after cessation of NAs.

BACKGROUND AIMS: Allogeneic hematopoietic stem cell transplantation from female donors to male recipients (female-to-male allo-HCT) is a well-established risk factor for a greater incidence of non-relapse mortality (NRM) and chronic graft-versus-host disease (GVHD). In contrast, unrelated cord blood transplantation (UCBT) is associated with a lower incidence of chronic GVHD. In this study, survival outcomes were compared between the UCBT and unrelated female-to-male bone marrow transplantation (UFMBMT) groups. METHODS: We evaluated male allo-HCT recipients who underwent UCBT or UFMBMT between 2012 and 2020 in Japan. There were 2517 cases in the UCBT group, 456 cases in the HLA-matched UFMBMT group and 457 cases in the HLA-mismatched UFMBMT group. RESULTS: HLA-mismatched UFMBMT was significantly associated with a decreased risk of relapse (hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.57-0.98], P = 0.033) and HLA-matched UFMBMT had the tendency of a decreased risk of relapse (HR 0.78; 95% CI 0.61-1.01, P = 0.059). HLA-matched UFMBMT was also associated with favorable OS (HR 0.82; 95% CI 0.69-0.97, P = 0.021). The relationship between the donor sources and relapse was similarly observed in the lymphoid malignancy cohort. CONCLUSIONS: The difference of graft-versus leukemia effect by H-Y immunity according to donor sources might contribute to the difference in clinical impact. It might be desirable for patients who could sufficiently wait for donor coordination to select BMT rather than UCBT, even if only unrelated female donors are available for male recipients.

Abstract Allogeneic hematopoietic cell transplantation between female donors and male recipients (female-to-male allo-HCT) is a well-established risk factor for inferior survival outcomes due to a higher incidence of graft-versus-host disease (GVHD). However, a clinical significance of anti-thymocyte globulin (ATG) in the female-to-male allo-HCT has not been elucidated. In this study, we retrospectively evaluated male patients who underwent allo-HCT between 2012 and 2019 in Japan. In the female-to-male allo-HCT cohort (n = 828), the use of ATG was not associated with a decreased risk of GVHD (HR of acute GVHD 0.691 [95% CI: 0.461–1.04], P = 0.074; HR of chronic GVHD 1.06 [95% CI: 0.738–1.52], P = 0.76), but was associated with favorable overall survival (OS) and a decreased risk of non-relapse mortality (NRM) (HR of OS 0.603 [95% CI: 0.400–0.909], P = 0.016; HR of NRM 0.506 [95% CI: 0.300–0.856], P = 0.011). The use of ATG in female-to-male allo-HCT resulted in survival outcomes that were almost equivalent to those in the male-to-male allo-HCT group. Therefore, GVHD prophylaxis with ATG might overcome the inferiority of survival outcomes in female-to-male allo-HCT.

Fatal cardiac complications can occur from the early to late phases after hematopoietic cell transplantation (HCT). Herein, the Japanese transplant registry database was used to retrospectively analyze health records of 33,791 allogeneic HCT recipients to elucidate the pathogenesis and risk factors involved. Overall, 527 patients died of cardiac complications at a median of 130 (range 0-3924) days after HCT. The cumulative incidence of fatal cardiac complications was 1.2% (95% confidence interval [CI]: 1.0-1.3) and 1.6% (95% CI: 1.5-1.8) at 1 and 5 years after HCT, respectively. Fatal cardiovascular events were significantly associated with an HCT-specific comorbidity index (HCT-CI) score of ≥1 specific to the three cardiovascular items, lower performance status, conditioning regimen cyclophosphamide dose of >120 mg/kg, and female sex. Cardiovascular death risk within 60 days after HCT was associated with the type of conditioning regimen, presence of bacterial or fungal infections at HCT, and number of blood transfusions. Contrastingly, late cardiovascular death beyond 1 year after HCT was associated with female sex and older age. Lower performance status and positive cardiovascular disease-related HCT-CI were risk factors for cardiac complications in all phases after HCT. Systematic follow-up may be necessary according to the patients' risk factors and conditions.

Anti-melanoma differentiation-associated gene 5 (MDA5) antibody is one of auto-immune antibodies which is associated with a rare subtype of dermatomyositis (DM), and MDA5-DM is well-characterized by rapid progressive interstitial lung disease (ILD) which in part resembles pulmonary complications after allogeneic hematopoietic cell transplantation (allo-HCT). However, previous studies about anti-MDA5 antibody after allo-HCT were extremely limited. Here, we present 4 cases of ILD with anti-MDA5 antibody after allo-HCT. All of the cases showed rapidly progressive clinical course and 3 of 4 cases died despite intensive immunosuppressive therapies which included prednisolone, cyclophosphamide and calcineurin inhibitor. Additionally, 3 of 4 cases had tested positive for anti-MDA5 antibody by using cryopreserved plasma which were collected about 2-3 months before the diagnosis of MDA5-DM-ILD. It suggests that an inflammatory condition due to MDA5-DM-ILD might have sub-clinically occurred before the development of respiratory failure. The current cases suggest that the clinical feature was relatively similar to classical MDA5-DM-ILD, although it is difficult to distinguish MDA5-DM-ILD from chronic GVHD and other pulmonary complications after allo-HCT. Since clinical courses of MDA5-DM-ILD is considerably aggressive, it is important to discriminate MDA5-DM-ILD from other complications after allo-HCT.

TEMPI syndrome is a rare disease associated with plasma cell neoplasms. Although previous studies have reported that bortezomib is effective as a 1st-line treatment for TEMPI syndrome, some cases are refractory to this treatment. Pomalidomide, a kind of immunomodulatory drugs, is widely used for the treatment of relapsed or refractory multiple myeloma and could be administered without dose modification in patients with renal dysfunction. We present a case of bortezomib-refractory TEMPI syndrome with renal insufficiency that was successfully treated with a combination of pomalidomide and low-dose dexamethasone with minimal adverse effects, followed by autologous hematopoietic stem cell transplantation. To the best of our knowledge, this is the first case of TEMPI syndrome that was successfully treated with pomalidomide. Pomalidomide may be suitable for patients who do not respond to a proteasome inhibitor-based treatment. In addition, a subsequent ASCT could also be effective for achieving a further treatment response.

Idiopathic pneumonia syndrome (IPS) is a fatal pulmonary complication after allogeneic hematopoietic stem cell transplantation (allo-HCT). However, it is often difficult to diagnose IPS, since a considerable number of IPS patients are critically ill, which makes it difficult for them to undergo bronchoscopy. In this study, we explored the risk factors of IPS based on two definitions. Definite IPS was diagnosed based on the results of bronchoscopy, whereas clinical IPS was diagnosed based on the clinical condition and bronchoscopy was not mandatory. Among 444 allo-HCT recipients at our center, 30 definite IPS and 54 clinical IPS were identified. In a multivariable analysis, a high ferritin level was associated with a higher incidence of definite IPS, whereas clinical IPS was frequently associated with older age, MAC, high ferritin level, low %DLCO and second allo-HCT due to graft failure. These risk factors may contribute to the accurate and early diagnosis of IPS.

The graft-versus-leukemia (GVL) effect is one of the curative mechanisms of allogeneic hematopoietic stem cell transplantation (allo-HCT). H-Y antigens, which are encoded by Y chromosome, are important targets of the GVL effect. Thus, deletion of the Y chromosome (del[Y]) might cause the GVL effect to deteriorate in a transplantation involving a female donor and male recipient, although the clinical significance of the del(Y) group remains to be elucidated. In this study, we evaluated adult male patients who underwent allo-HCT between 2010 and 2019 in Japan. There were 155 cases in the del(Y) group and 4149 cases without del(Y) who underwent female-to-male allo-HCT. Del(Y) was significantly associated with inferior overall survival (hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.00-1.53; P = .049) and an increased risk of relapse (HR, 1.40; 95% CI, 1.08-1.80; P = .0098) in multivariate analyses. There was no significant difference in nonrelapse mortality between recipients with and without del(Y) (HR, 1.08; 95% CI, 0.769-1.51; P = .67). In contrast, del(Y) was not significantly associated with any clinical outcomes in the cohort of male-to-male allo-HCT. A higher incidence of relapse might have been caused by attenuation of the GVL effect resulting from a lack of H-Y antigens. Because a GVL effect resulting from sex mismatch may not be expected in men with del(Y) who undergo allo-HCT with a female donor, additional post-allo-HCT strategies might be required to prevent disease relapse.

A preemptive strategy has successfully decreased cytomegalovirus (CMV) disease after allogeneic hematopoietic cell transplantation (HCT).However, some recipients still develop CMV gastroenteritis, especially after acute graft-versus-host disease (aGVHD), and its incidence, risk factors, and prognostic impact remain to be elucidated.We retrospectively analyzed 3759 consecutive adult patientswho developed grade II-IV aGVHD using a Japanese registry database. The cumulative incidence of CMV gastroenteritiswas 5.7%by day 365 fromthe development of grade II-IV aGVHD. Advanced age (hazard ratio [HR], 1.60; 95%confidence interval [CI], 1.16-2.22; P=.004), GVHDprophylaxiswithmycophenolate mofetil and calcineurin inhibitor (HR, 1.73; 95%CI, 1.08-2.77; P=.024), lower-gut aGVHD (HR, 2.17; 95%CI, 1.58-2.98; P<.001), and the use of systemic steroids (HR, 1.78; 95%CI, 1.16-2.74; P5.008)were independent risk factors for CMV gastroenteritis. Development of CMV gastroenteritis was associated with an increased risk of nonrelapsemortality (HR, 1.89; 95%CI, 1.50-2.39; P<.001). Moreover, letermovir prophylaxis significantly reduced both the incidence of CMV gastroenteritis (HR, 0.50; 95%CI, 0.25-0.99; P=.047) and the risk of nonrelapsemortality (HR, 0.72; 95%CI, 0.52- 0.99; P=.043). In summary, CMV gastroenteritis is a life-threatening complication that sets the need for preventive strategieswith letermovir and targeted surveillance.

There is a matter of debate about the clinical impact of cytomegalovirus (CMV) reactivation on the development of late-onset invasive aspergillosis (IA), which occurs 40 days or later after allogeneic hematopoietic stem cell transplantation (HSCT). Using a Japanese transplant registry database, we analyzed the risk factors for the development of late-onset IA in 21,015 patients who underwent their first allogeneic HSCT between 2006 and 2017. CMV reactivation was defined as the initiation of preemptive anti-CMV antiviral therapy. Overall, there were 582 cases of late-onset IA, which occurred at a median of 95 days after HSCT. The 2-year cumulative incidence was 3.4% (95% confidence interval (CI), 3.0-3.9) in patients with CMV reactivation within 40 days after HSCT and 2.5% (95% CI, 2.3-2.8) in those without it (P < 0.001). In a multivariate analysis, CMV reactivation as a time-dependent covariate was significantly associated with the development of late-onset IA (hazard ratio (HR) 1.40, P < 0.001), as well as grade II-IV acute GVHD, age > 50 and HCT-CI ≥ 3 in the entire cohort. If we focus on the subgroup without grade II-IV acute GVHD, which is generally an indication for systemic corticosteroid therapy (n = 12,622), CMV reactivation was still a significant factor for the development of late-onset IA (HR 1.37, P = 0.045) as well as age > 50 years, HCT-CI ≥ 3, and cord blood transplantation. In conclusion, CMV reactivation was associated with an increased risk of late-onset IA after allogeneic HSCT independently of acute GVHD. Close monitoring for late-onset IA is necessary for patients who develop CMV reactivation even without grade II-IV acute GVHD.

Most acute leukemia patients receive consecutive intensive chemotherapy, which usually takes several months before allogeneic hematopoietic stem cell transplantation (allo-HCT). Intensive chemotherapy often induces gastrointestinal adverse events. These adverse events leave patients in a state of malnutrition, leading to a reduction in body weight. In this study, we analyzed the impact of body weight loss before allo-HCT on survival outcomes of acute leukemia patients (acute myeloid leukemia, acute lymphoid leukemia and mixed phenotype acute leukemia). A loss of body weight (LBW), which was a reduction of body weight from diagnosis or relapse to transplantation, was calculated in 182 acute leukemia patients who received first allo-HCT at our center between June 2006 and September 2019. A receiver operating characteristics curve for nonrelapse mortality (NRM) was plotted for defining the cut-off value of LBW. The cutoff value of LBW was defined as 13.2%. A higher LBW was significantly associated with inferior NRM and overall survival (OS) (2-year [2y] NRM 36.1% versus 11.5%, P = .0025; 2y-OS 39.9% versus 65.8%, P = .020). The adverse impact of LBW was also confirmed in multivariate analyses for NRM and OS (HR of NRM 2.74 [1.25-6.03], P = .0012; HR of OS 2.06 [1.00-3.07], P = .0049). The main cause of death included disease progression (n = 34) and infection (n = 35). Death cause by infection was more frequently observed in the high-LBW group (15 cases [35.7%] versus 20 cases [14.3%]; P = .0035). In addition, subgroup analyses based on a combination of the body mass index at diagnosis and LBW were performed. When the non-overweight-low LBW group (body mass index [BMI] ≤25 and LBW ≤13.2%) was used as a reference in multivariate analysis, the overweight-high LBW group (BMI >25 and LBW >13.2%) showed an increased risk of poor survival outcomes (HR of NRM 4.27 [95% confidence interval {CI}, 1.82-10.0], P < .001; HR of OS 1.93 [95%, CI 1.00-3.71], P = .050). High LBW was significantly associated with inferior survival outcomes, and the adverse effect of malnutrition might be greater than the favorable effect of the reduction in overweight.

The pulmonary function test (PFT) is an important test for risk stratification before allogeneic transplantation (allo-HCT). However, it might be preferable to avoid PFT as much as possible in the recent era of coronavirus disease 2019 (COVID-19), because PFT requires forced expirations and might produce aerosols, increasing the risk of COVID-19 transmission. Therefore, we tried to predict normal PFT results before allo-HCT based on computed tomography (CT) findings. This study included 390 allo-HCT recipients at our center for whom lung CT images and PFT results before allo-HCT were available. Abnormal CT findings were less likely to be observed in the normal PFT group (47.0% versus 67.4%, P = .015), with a high negative predictive value of 92.9%. In a multivariate analysis, normal CT was significantly associated with normal PFT (odds ratio, 2.47; 95% confidence interval, 1.22 to 4.97; P = .012). A model for predicting normal PFT was constructed based on the results of a multivariate analysis, and the area under the curve of the receiver operating characteristic analysis was 0.656, which gave a sensitivity of 45.5% and a specificity of 86.0%. The relatively high specificity of the model suggested that PFT can be omitted in patients with normal CT findings before allo-HCT.

Allogeneic hematopoietic transplantation (allo-HCT) is still associated with significant morbidity and mortality, and risk stratification is critical. In this study, we analyzed the relationship between blood pressure control early after allo-HCT and survival outcomes. All patients who survived longer than 28 days after allo-HCT at our center between June 2007 and June 2018 (n = 353) were included, and the average systolic blood pressure (asBP) from 1 to 28 days after allo-HCT was calculated. According to the results of a ROC curve analysis, an asBP of 131 mmHg was defined as a cut-off value between high and low asBP groups. Non-relapse mortality (NRM) and OS were significantly inferior in the high asBP group (2-year-NRM 28.0% vs 11.1%, P < 0.001; 2-year-OS 46.7% vs 65.7%, P = 0.001). In addition, baseline asBP before commencement of the conditioning regimen and elevation of asBP (asBP - baseline asBP) were both associated with inferior NRM. While these results were also observed in the younger patients (≤ 50 years), no relationship was observed in the older patients (> 50 years). High blood pressure within 28 days after allo-HCT was associated with inferior survival outcomes, especially in patients younger than 50 years.

Pulmonary complications are fatal adverse events after allogeneic hematopoietic cell transplantation (allo-HCT). On the other hand, smoking is a well-known risk factor for various pulmonary diseases and also increases the incidence of pulmonary complications and overall mortality in allo-HCT recipients. In this study, we retrospectively assessed the impact of smoking intensity on survival outcomes. This study included consecutive allo-HCT recipients at our center between June 2007 and May 2019 whose smoking profiles were available (n = 408); they were divided into high (pack-years >10, n = 171) and low (pack-years ≤10, n = 231) pack-years groups. In univariate analyses, nonrelapse mortality (NRM) and overall survival (OS) were significantly inferior in the high pack-years group (1-year NRM 26.6% versus 13.9%, P < .001; 1-year OS 58.4% versus 70.1%, P = .0067). However, this association was not observed in multivariate analyses. In subgroup analyses according to sex, the survival outcomes in the high pack-years group were significantly inferior in males (NRM hazard ratio [HR], 2.24 [95% confidence interval (CI), 1.23 to 4.07], P = .0082; OS HR, 1.54 [95% CI, 1.04 to 2.28], P = .031), but not in females (NRM HR, 0.587 [95% CI, 0.241 to 1.43], P = .24; OS HR, 0.689 [95% CI, 0.400 to 1.19], P = .18). In summary, high pack-years were associated with inferior survival of allo-HCT recipients, especially in males.

The optimal treatment strategy for gastrointestinal graft-versus-host disease (GI-GVHD) after allogeneic hematopoietic cell transplantation remains to be established. We retrospectively analyzed 68 cases of GI-GVHD at our institution between 2007 and 2017. The survival outcomes were significantly inferior in patients who did not respond to the first-line treatment (1-year overall survival 27.3 vs 69.2%, P = 0.0017; non-relapse mortality 50.0 vs 18.6%, P = 0.026). After subsequent treatments, 18 patients were refractory to all steroid-based treatments such as steroid pulse therapy and oral beclomethasone dipropionate (BDP). However, these steroid-refractory cases showed a gradual increase in the response rate after the initial diagnosis of steroid refractoriness. This result may be explained by the problem of evaluating the response based solely on the volume of diarrhea, i.e., severe mucosal damage due to refractory GI-GVHD may require a long recovery and sometimes be complicated with other diseases. In conclusion, patients with GI-GVHD who failed to respond to the first-line treatment had inferior survival. However, later improvement may be observed without additional immunosuppressant other than steroid among patients who initially do not respond to steroid therapy. It is important to repeat colonoscopy in patients with refractory GI-GVHD to monitor the activity of GVHD.

High-dose melphalan followed by autologous hematopoietic stem cell transplantation (ASCT) is a standard treatment for younger myeloma patients. However, the correlation between its toxicity and renal impairment is not clear. We analyzed this relationship, focusing on estimated glomerular filtration rate (eGFR) as an index of renal function. We evaluated 78 multiple myeloma patients who underwent ASCT following high-dose melphalan at our center. Patients were divided into a higher eGFR group (eGFR ≥ 60) and a lower eGFR group (eGFR < 60). Multivariate analyses revealed that lower eGFR was independently associated with alkaline phosphatase elevation (OR 10.2, P = 0.038), mucositis (OR 10.5, P = 0.032), grade 2-4 co-elevation of both aspartate aminotransferase and alanine aminotransferase (OR 21.3, P = 0.016), delay of reticulocyte engraftment (HR 0.524, P = 0.034), and delay of platelet engraftment (HR 0.535, P = 0.0016). However, lower eGFR was not correlated with overall survival or time-to-next treatment. In summary, renal dysfunction secondary to administration of high-dose melphalan was associated with increased hepatic and mucosal toxicity and delay of hematological recovery, but did not affect survival outcomes.

Central nervous system lomentosporiosis is a rare pathological condition in immunocompromised patients. We describe a fatal case of meningitis caused by Lomentospora prolificans (which was previously named Scedosporium prolificans), after an allogeneic hematopoietic stem cell transplantation (allo-HSCT). To our knowledge, no cases of Lomentospora meningitis following allo-HSCT have been reported previously. Particularly in neutropenic patients, it is important to consider L. prolificans when a fungal infection is suspected and antifungal agents are ineffective.