Decision analysis for transplant candidates with primary myelofibrosis in the ruxolitinib era.

The recent progress with ruxolitinib treatment might improve quality of life as well as overall survival in patients with primary myelofibrosis. Therefore, the optimal timing of allogeneic hematopoietic cell transplantation (HCT) in the ruxolitinib era remains to be elucidated. We constructed a Markov model to simulate the 5-year clinical course of transplant candidates with primary myelofibrosis and compared outcomes between those who underwent immediate HCT and those whose HCT was delayed until after ruxolitinib failure. Since older age was associated with an increased risk of mortality, we analyzed patients aged <60 and ≥60 years separately in subgroup analyses. Life expectancy was consistently longer in the groups undergoing delayed HCT after ruxolitinib failure regardless of the patients' age. Regarding quality-adjusted life years, a baseline analysis showed that immediate HCT was inferior to delayed HCT after ruxolitinib failure (2.19 vs. 2.26). In patients aged <60 years, immediate HCT was equivalent to delayed HCT after ruxolitinib failure (2.31 vs. 2.31). On the other hand, in patients aged ≥60 years, immediate HCT was inferior to delayed HCT after ruxolitinib failure (1.98 vs. 2.21). A one-way sensitivity analysis showed that the utility of being alive without chronic graft-versus-host disease after immediate HCT was the most influential parameter for quality-adjusted life years, and that a value higher than 0.836 could reverse the superiority of delayed HCT after ruxolitinib failure. As a result, delayed HCT after ruxolitinib failure is expected to be superior to immediate HCT, especially in patients aged ≥60 years, and is also a promising strategy even in those aged <60 years.

Clinical impact of a change in antibiotics or the addition of glycopeptide antibiotics for persistent febrile neutropenia after autologous stem cell transplantation.

BACKGROUND: A change in empirical antibiotics or the addition of glycopeptide antibiotics is often applied in cases of persistent febrile neutropenia (FN) despite the administration of broad-spectrum antibiotics. However, the clinical benefit of these approaches remains unclear. METHODS: We conducted a retrospective study to evaluate the effectiveness of a change in antibiotics or the addition of glycopeptide antibiotics for persistent FN after autologous hematopoietic cell transplantation (auto-HCT). We retrospectively reviewed the records of 208 patients who received auto-HCT at our institution between 2007 and 2019. FN that lasted for 4 days or longer was defined as persistent FN. We compared the time to defervescence between patients whose initial antibiotics were changed and/or who additionally received glycopeptide antibiotics, and those without these antibiotic modifications. RESULTS: Among patients who fulfilled the criteria of persistent FN (n = 125), changes in antibiotics were not significantly associated with the time to defervescence in a multivariate analysis (hazard ratio [HR] 0.72, p = 0.27). On the other hand, the addition of glycopeptide antibiotics was paradoxically associated with a delay in defervescence (HR 0.56, p = 0.033). CONCLUSIONS: Although there may be differences in patient backgrounds, no significant differences were observed in either a univariate or multivariate analysis. Since neither a change in antibiotics nor the addition of glycopeptide antibiotics was associated with earlier defervescence in persistent FN after auto-HCT, routine antibiotic modifications might not be necessary in this setting.

Gene expression and TCR amino acid sequences selected by HLA-A02:01-restricted CTLs specific to HTLV-1 in ATL patients.

Adult T-cell leukaemia/lymphoma (ATL) is an aggressive malignancy of peripheral T cells caused by human T-cell lymphotropic virus type-1 (HTLV-1). Tax is the most important regulatory protein for HTLV-1. We aimed to reveal a unique amino acid sequence (AA) of complementarity-determining region 3 (CDR3) of the T-cell receptor (TCR)ß and TCRα chains of HLA-A*02:01-restricted Tax11-19 -specific cytotoxic T cells (Tax-CTLs). The gene expression profiles (GEP) of Tax-CTLs were assessed by the next-generation sequence (NGS) method with SMARTer technology. Tax-CTLs seemed to be oligoclonal, and their gene compositions were skewed. The unique motifs of 'DSWGK' in TCRα and 'LAG' in TCRß at CDR3 were observed in almost all patients. Tax-CTL clones harbouring the 'LAG' motif with BV28 had a higher binding score than those without either of them, besides a higher binding score associated with longer survival. Tax-CTLs established from a single cell showed killing activities against Tax-peptide-pulsed HLA-A2+ T2 cell lines. GEP of Tax-CTLs revealed that genes associated with immune response activity were well preserved in long-term survivors with stable status. These methods and results can help us better understand immunity against ATL, and should contribute to future studies on the clinical application of adoptive T-cell therapies.

Clinical features of febrile neutropenia and bloodstream infection in autologous hematopoietic cell transplantation: Comparison to those in intensive chemotherapy for acute myeloid leukemia.

BACKGROUND: In autologous hematopoietic cell transplantation (HCT), myelosuppression and mucosal damage are more severe than those in conventional chemotherapy because of high-dose chemotherapy, but the duration of neutropenia is shorter due to stem cell rescue. METHODS: We retrospectively evaluated febrile neutropenia (FN) and bloodstream infection (BSI) in 208 patients who underwent their first autologous HCT at our institution between 2007 and 2019. They were compared to those in patients who underwent intensive chemotherapy for acute myeloid leukemia (AML) (130 induction/salvage and 191 consolidation). RESULTS: The median neutropenic period in autologous HCT, AML induction/salvage and consolidation was 9, 26.5, and 19 days, respectively. The incidence of FN was 93.8%, 92.3%, and 81.7%, and that of BSI in initial FN was 7.2%, 7.5% and 26.3%, respectively. The incidence of oral mucositis (≥ grade 2) was 63.1%, 9.2% and 12.2%, and that of diarrhea (≥ grade 2) was 53.3%, 9.2% and 6.4%, respectively. Although there were significant differences in the incidence of shaking chills, the degree of fever and the value of CRP between patients with and without BSI in initial FN of AML chemotherapy, no significant risk factors or predictive factors for BSI were identified in autologous HCT. CONCLUSIONS: The profile of infectious complications in autologous HCT was characterized by a high incidence of FN maybe due to mucosal damage. On the other hand, the incidence of BSI was lower compared to that in AML consolidation chemotherapy.

Chronic active Epstein-Bar virus infection complicated by pulmonary artery hypertension.

Chronic active Epstein-Bar virus infection (CAEBV) is known to cause various symptoms. Although pulmonary artery hypertension (PAH) has been reported as a cardiovascular complication of CAEBV, the mechanisms of PAH and the effects of treatment have not been fully elucidated. We experienced 4 adult patients with CAEBV complicated by PAH. All of them received treatment for PAH with a vasodilator followed by chemotherapy with or without allogeneic hematopoietic cell transplantation for CAEBV. In all of these patients, the transtricuspid pressure gradient improved under treatment with vasodilator, and further improvement was observed under treatment for CAEBV in 3 patients. Autopsy was performed in 2 patients, which revealed EBER-positive cells and a change in the pulmonary artery at each stage in the pathology. In conclusion, EBV-infected cells can cause vasculitis and finally PAH. However, PAH complicated with CAEBV can be improved by PAH medication and treatment of CAEBV.

[Anti-MDA5 antibody-positive rapidly progressive interstitial lung disease after allogeneic hematopoietic cell transplantation successfully treated with triple immunosuppressive therapy].

A 34-year-old man with KMT2A-MLLT1 acute myeloid leukemia in first complete remission underwent allogeneic peripheral blood stem cell transplantation from his HLA-matched sister after conditioning with busulfan/cyclophosphamide. He did not have severe graft-versus-host disease, but he developed interstitial pneumonia six months after transplantation when his oral cyclosporine A (CsA) dose was reduced to 10 mg/day. He was given prednisolone (PSL), which temporarily improved his respiratory condition, but he quickly deteriorated when PSL was reduced. Anti-MDA5 antibody was found to be positive after additional testing, and a three-drug combination of intravenous cyclophosphamide+PSL+CsA was initiated for anti-MDA5 antibody positive rapidly progressive interstitial lung disease, which was effective for interstitial pneumonia. He received a successful living-donor lung transplant from his younger brother and sister. We present a case of rapidly progressive anti-MDA5 antibody positive interstitial lung disease in which the patient's respiratory condition improved after triple therapy and subsequent living-donor lung transplantation.

Successful Treatment of the TEMPI Syndrome with Pomalidomide Plus Dexamethasone Followed by Autologous Stem Cell Transplantation.

TEMPI syndrome is a rare disease associated with plasma cell neoplasms. Although previous studies have reported that bortezomib is effective as a first-line treatment for TEMPI syndrome, some cases are refractory to this treatment. Pomalidomide, a kind of immunomodulatory drug, 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 (ASCT). 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.

Association between the kinetics of cytomegalovirus reactivation in terms of the area under the curve of cytomegalovirus antigenemia and non-relapse mortality after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: We assessed the kinetics of cytomegalovirus (CMV) reactivation using the area under the curve (AUC), which simultaneously reflects both the viral load at each time point and the duration of CMV antigenemia (CMV-AG). METHODS: We performed a single-institute retrospective analysis in patients who received allogeneic hematopoietic stem cell transplantation (HSCT) between 2007 and 2017 and survived more than 100 days after HSCT. The AUC of CMV-AG (CMV-AUC) was calculated by a trapezoidal method using the number of CMV-AG tested by the C10/C11 method after logarithmic transformation, and plotted weekly up to day 100. RESULTS: CMV reactivation was observed in 195 cases and the median CMV-AUC for CMV-reactivated patients was 8.7 (range 0.5-30.7). Older age, corticosteroid administration, CMV-seropositive transplant recipients, HSCT from an unrelated donor, and underlying diseases were independent predictive factors for higher CMV-AUC. Higher CMV-AUC was associated with poor overall survival (OS) with borderline significance in a univariate analysis (p = .07), but was not significant in a multivariate analysis. Older age, high-risk disease status, and female gender were identified as significant factors associated with poor OS in this study. On the other hand, CMV-AUC (hazard ratio: no reactivation reference, low 0.98, high 2.49, p < .01), older age, HCT-CI ≥3, and corticosteroid administration were identified as significant factors associated with increased incidence of non-relapse mortality (NRM). CONCLUSIONS: The kinetics of CMV reactivation in terms of CMV-AUC reflect both the severity and duration of CMV reactivation. High CMV-AUC was associated with an increased incidence of NRM in survivors over 100 days.

Association of the areas over and under the lymphocyte curve with cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: We retrospectively compared the impact of the areas over and under the lymphocyte curve (L_AOC vs L_AUC) on cytomegalovirus (CMV) reactivation after allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: Among 394 consecutive patients who underwent their first allogeneic HSCT at our center between 2007 and 2018, 301 patients met the inclusion criteria. L_AOC was calculated as the area over the lymphocyte curve during lymphopenia (absolute lymphocyte count [ALC] <700/µL). We calculated L_AOC and L_AUC from day 0 to day 15 (L_AOC15, L_AUC15) and from day 0 to day 30 (L_AOC30, L_AUC30). RESULTS: CMV antigenemia was defined as more than 3 cells/2 slides by the C10/11 method and detected in 204 cases (CMV reactivation) at a median of 39 days after HSCT. Although there were significant differences in L_AOC15, L_AOC30, L_AUC15, and L_AUC30 between patients with and without CMV reactivation, there was no difference in accuracy for predicting CMV reactivation between L_AOC and L_AUC. In a multivariate analysis, L_AOC15 and L_AUC15 were each identified as independent predictive factors for CMV reactivation, along with advanced age and CMV serostatus. However, ALC at day 14 or day 21 was as accurate as area-based indexes such as L_AOC15 and L_AUC15. L_AOC15 and L_AUC15 were significantly associated with longer duration of anti-CMV antiviral therapy while ALC was not. CONCLUSIONS: L_AOC15 and L_AUC15 had similar impacts on CMV reactivation. Although these area-based indexes were not superior to ALC for predicting CMV reactivation, they might predict patients who need longer duration of antiviral therapy more accurately.

Pre-Hematopoietic Stem Cell Transplantation Lung Computed Tomography as an Alternative to the Pulmonary Function Test during the COVID-19 Pandemic.

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.

Impact of neutropenia evaluated in terms of the D-index on invasive fungal disease while on empiric or preemptive antifungal treatment strategy in the early phase after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: We retrospectively evaluated the association between the D-index, which reflects both the depth and duration of neutropenia, and proven/probable invasive fungal disease (IFD) early after allogeneic hematopoietic stem cell transplantation (HSCT) at our center (n = 394). METHODS: The D-index was defined as the area over the neutrophil curve during neutropenia. The cumulative D-index from the start of neutropenia until the development of infection (c-D-index) was also evaluated as a real-time assessment of neutropenia. RESULTS: There were 19 cases of early proven/probable IFD before and within 1 week after engraftment. Fifteen cases (78.9%) were seen as breakthrough infection while on empiric (n = 7), preemptive (n = 4) or prophylactic (n = 4) antifungal administration with mold-active agents. The c-D-index and lower performance status were identified as independent significant predictive factors for IFD. A receiver operating characteristic (ROC) curve analysis showed that the D-index and c-D-index were more accurate than the simple duration of neutropenia and as accurate as the duration of profound neutropenia for predicting IFD. The sensitivity, specificity, and positive and negative predictive values of the c-D-index using an appropriate cutoff (CO) value (10 644) determined by ROC curve analysis were 73.1%, 63.2%, 9.1%, and 97.9%, respectively. The advantage of the c-D-index to cumulative days of neutropenia in terms of positive and negative predictive values seemed to be small. CONCLUSIONS: The appropriate CO value for the c-D-index for predicting IFD was as high as 10 644 in allogeneic HSCT with a more frequent use of empiric antifungal therapy. The c-D-index is useful for assessing the risk of breakthrough IFD.

Recurrent bicycle falls by an elderly man who developed multiple intramuscular abscesses associated with urine leakage secondary to posterior urethral injury caused by pelvic ring disruption.

Key Clinical Message: With the aging of the population, physicians need to pay more attention to assessing the presence or absence of pelvic fractures and urinary retention associated with urethral injury due to such fractures in the elderly when falling from bicycles. Abstract: Walking ability does not rule out the presence of pelvic fractures. Many geriatric patients are likely to fall off bicycles. Physicians should pay more attention when assessing complications related to urethral trauma caused by pelvic fractures in the elderly after falling from bicycles.

Very early death within 30 days after diagnosis in patients with acute myeloid leukemia.

Acute myeloid leukemia (AML) is a malignancy that requires immediate treatment. However, the factors that predict very early mortality are not well known. We retrospectively analyzed 70 patients who were newly diagnosed with AML at our institution between 2014 and 2020. Very early death within 30 days after the initial consultation with a hematologist occurred in eight patients, including seven men. They were older than 30-day survivors (70.5 vs. 47 years, P < 0.01). In addition, four patients with a low score on the Glasgow Coma Scale (GCS) at diagnosis died within 30 days, and half of the early death group died due to cerebral hemorrhage. We next tried to predict early death using a ROC curve. Age, hemoglobin (Hb), estimated glomerular filtration rate (eGFR) and the international normalized ratio of prothrombin time (PT-INR) all had an area under the curve of greater than 0.8 for predicting very early death. A multivariate analysis revealed that older age (OR = 1.14, P = 0.033), Hb (OR = 0.48, P = 0.05), and low GCS (OR = 140.0, P = 0.0073) were significantly associated with very early death. Further studies will be needed to confirm which patients are at high risk for early death and to improve the treatment strategy for such patients.

Plasma ubiquitin C-terminal hydrolase-L1 (UCH-L1) level as a blood biomarker of neurological damage after allogeneic hematopoietic cell transplantation.

Several biofluid-based biomarkers for traumatic brain injury show promise for use in diagnosis and outcome prediction. In contrast, few studies have investigated biomarkers for non-traumatic brain injury. We focused on ubiquitin C-terminal hydrolase-L1 (UCH-L1), which has been proposed as a screening tool for traumatic brain injury, and investigated whether the plasma UCH-L1 level could also be a useful biomarker in patients with non-traumatic brain injury. We measured UCH-L1 in 25 patients who had experienced neurological complications after allogeneic hematopoietic cell transplantation (HCT) and 22 control patients without any complications or graft-versus-host disease. Although UCH-L1 levels before HCT did not differ significantly (P = 0.053), levels after HCT were higher in patients with neurological complications compared with the control group (P < 0.001). At a UCH-L1 cutoff value of 0.072 ng/ml, sensitivity was 68.0% and specificity was 100%. The statistical power of UCH-L1 for neurological complications seemed to be higher than that of CT and comparable to that of MRI. Thus, increased levels of UCH-L1 might reflect the presence of neurological damage even in patients with non-traumatic brain injury. Further large cohort investigations are warranted.

Substitution of calcineurin inhibitors with corticosteroids after allogeneic hematopoietic cell transplantation.

Combination of calcineurin inhibitors (CIs) with short-term methotrexate is a standard prophylactic regimen for graft-versus-host disease (GVHD). However, it is sometimes difficult to continue CIs due to adverse effects, such as renal impairment and fluid overload. In such cases, we replace CIs with corticosteroids, considering that full dose of CIs is equivalent to prednisolone (PSL) at 1 mg/kg. We retrospectively evaluated the clinical significance of replacement of CIs with corticosteroids after allogeneic hematopoietic cell transplantation (HCT). We evaluated 42 patients switched from CIs to corticosteroids within 90 days among the 479 patients who underwent allogeneic HCT at our center between 2007 and 2019. Renal impairment (n = 33), fluid overload (n = 13), and thrombotic microangiopathy (n = 3) were the main reasons for switching. Although creatinine and body weight returned to baseline at 4 weeks after switching, 100-day non-relapse mortality was high (57.1%). Grade II-IV acute GVHD was seen in 10 (24.4%) patients who did not have it before switching treatment (n = 41). In conclusion, CIs were switched to corticosteroids in patients with severe clinical conditions. The incidence of acute GVHD was acceptable. Although the short-term mortality rate was high, improvement of renal function or fluid overload was observed in a certain proportion of the patients.

Clinical Impact of Pretransplantation Physical Function on Transplantation after Allogeneic Hematopoietic Cell Transplantation in Older Adults.

Clinical research regarding the impact of pretransplantation physical function on transplantation outcomes in older adults remains limited. We retrospectively reviewed the charts of 150 consecutive patients age >55 years who underwent their first allogeneic hematopoietic cell transplantation (HCT) at our center between 2010 and 2021. We evaluated the clinical impact of pretransplantation physical function, including hand grip strength (HGS), knee extension strength (KES), and distance covered in a 6-minute walk test (6MWT), along with other clinical factors, on transplantation outcomes such as overall survival (OS), nonrelapse mortality (NRM), and cumulative incidence of disease relapse (CIR). There was no difference in OS, NRM, or CIR among the 3 age groups studied (56 to 60 years, 61 to 65 years, and 66 to 70 years). With regard to physical function tests, we divided the study patients into 2 groups based on the median HGS, KES, and 6MWT values: higher physical function and lower physical function groups. Because there were significant differences in HGS and KES between male and female patients, sex-specific threshold values were used. In a univariate analysis, OS tended to be better in the higher physical function group compared with the lower physical function group (4-year OS, 42.0% versus 32.0% in HGS, P = .14; 44.8% versus 37.8% in KES, P = .17; 46.7% versus 30.5% in 6MWT, P = .099). NRM was significantly lower in the higher physical function group (4-year NRM, 25.5% versus 39.9% in HGS, P = .045; 17.7% versus 38.0% in KES, P = .005; 22.5% versus 43.4% in 6MWT, P = .033). There was no significant difference in CIR between the higher and lower physical function groups (4-year CIR, 34.6% versus 28.7% in HGS, P = .38; 38.5% versus 25.8% in KES, P = .20; 33.0% versus 27.0% in 6MWT, P = .42). In multivariate analysis, the higher KES group (hazard ratio [HR], .54; 95% confidence interval [CI], .32 to .90) was significantly associated with better OS, as were female sex (HR, .48; 95% CI, .26 to .89) and low/intermediate Disease Risk Index (HR, 3.59; 95% CI, 2.04 to 6.31). Higher KES (HR, .37; 95% CI, .17 to .83) and female sex (HR .36; 95% CI, .13 to .998) were significantly associated with a reduced risk of NRM. Higher HGS and higher 6MWT tended to be associated with a reduced risk of NRM, but this trend was not statistically significant. Pretransplantation physical function, particularly the strength of the lower extremities, but not chronological age, is associated with NRM and OS after allogeneic HCT in adults age >55 years.

Emergence of clone with PHF6 nonsense mutation in chronic myelomonocytic leukemia at relapse after allogeneic HCT.

Disease relapse is a major cause of treatment failure after allogeneic hematopoietic cell transplantation (HCT) and the mechanisms of relapse remain unclear. We encountered a 58-year-old man with chronic myelomonocytic leukemia (CMML) that relapsed after haploidentical HCT from his daughter. Peripheral blood samples collected at HCT and at relapse were analyzed, and CD14+/CD16- monocytes that typically accumulate in CMML were isolated by flow cytometry. Whole-exome sequencing of the monocytes revealed 8 common mutations in CMML at HCT. In addition, a PHF6 nonsense mutation not detected at HCT was detected at relapse. RNA sequencing could not detect changes in expression of HLA or immune-checkpoint molecules, which are important mechanisms of immune evasion. However, gene set enrichment analysis (GSEA) revealed that a TNF-α signaling pathway was downregulated at relapse. Ubiquitination of histone H2B at lysine residue 120 (H2BK120ub) at relapse was significantly decreased at the protein level, indicating that PHF6 loss might downregulate a TNF-α signaling pathway by reduction of H2BK120ub. This case illustrates that PHF6 loss contributes to a competitive advantage for the clone under stress conditions and leads to relapse after HCT.

Low-Intensity Immunosuppressive Therapy for Chronic Graft-versus-Host Disease.

In general, the initial systemic treatment for chronic graft-versus-host disease (cGVHD) is 0.5 to 1 mg/kg of prednisolone (PSL). However, patients without high-risk features are sometimes treated with a calcineurin inhibitor (CI) or PSL at lower doses. Here we retrospectively evaluated patients with cGVHD who were treated with low-intensity immunosuppressive therapy (IST), defined as CI with or without PSL at <.25 mg/kg. The primary outcome was failure-free survival (FFS), and we evaluated current FFS (cFFS) considering the state transition between low-intensity IST and high-intensity IST defined as the administration of >.25 mg/kg of PSL or immunosuppressants other than CI or PSL. Fifty-four patients were evaluated, few of whom had a low performance status and intestinal or lung involvement. FFS at 24 months after treatment was 50.0% (95% confidence interval [CI], 36.0% to 62.3%). Risk factors for failure were use of IST before 6 months post-transplantation (hazard ratio [HR], 2.16; 95% CI, 1.05 to 2.16; P = .036) and transplantation from a female donor to a male recipient (HR, 2.65; 95% CI, 1.29 to 5.48; P = .008). At 6 months, 44.0% of patients had achieved a complete or partial response without a change in treatment. cFFS at 36 months was 67.0% (95% CI, 51.8 to 79.4%), which was greater than simple FFS (43.2%; 95% CI, 36.6% to 52.8%). There was no difference in simple FFS according to the National Institutes of Health global score. However, cFFS at 3 years varied according to the global score (mild, 91.7%; moderate, 64.0%; severe, 43.8%; P = .036). Low-intensity IST for cGVHD was effective in patients without high-risk features.

Pancreatic atrophy and recovery after allogeneic hematopoietic cell transplantation.

BACKGROUND: Pancreatic atrophy after allogeneic hematopoietic cell transplantation (HCT) is one of the symptoms associated with chronic graft-versus-host disease (GVHD). Although pancreatic atrophy has been considered to cause exocrine insufficiency and weight loss, it is not yet clear what kinds of recipients can be expected to recover their body weight (BW) or pancreatic thickness. In addition, the effect of pancreatic atrophy on the prognosis has not been clarified. METHODS: We retrospectively analyzed 170 recipients who received allogeneic bone marrow transplantation or peripheral blood stem cell transplantation, and evaluated them using the CT scan images obtained closest to 1, 2, 3, and 4 years after HCT. RESULTS: Fifty-five recipients (32.4%) demonstrated pancreatic atrophy, and 11 (20%) of them recovered their pancreatic thickness. While recipients without pancreatic atrophy gradually recovered their BW (P < 0.001), those with atrophy did not (P = 0.12). Moderate and severe chronic GVHD tended to be slightly more common in the atrophy group (47.3% vs 38.3%), whereas the pancreatic thickness tended to recover in these recipients (30.8% vs 10.3%). HCT from a female donor to a male recipient showed superior pancreatic recovery compared to other donor and recipient sex combinations. Pancreatic atrophy treated as a significantly associated with inferior survival (HR 4.91, P < 0.001) and an increased risk of non-relapse mortality (HR 8.75, P < 0.001). CONCLUSIONS: These results suggest that it is important to monitor pancreatic thickness after HCT. Further prospective investigations are warranted to clarify the significance of pancreatic atrophy on clinical outcomes.