Lymphopenia at diagnosis predicts survival of patients with immunodeficiency-associated lymphoproliferative disorders

The number of patients who are administered immunosuppressive agents has been increasing. Accordingly, more patients face higher risks for developing immunodeficiency-associated lymphoproliferative disorders (LPD). Although immunodeficiency-associated LPD are distinct from other lymphoid neoplasms in terms of their immunocompromised backgrounds, little is known about the impact of lymphopenia at diagnosis on survival in patients with these LPD. Seventy-one immunodeficiency-associated LPD in Kyoto University Hospital (post-transplant LPD (PTLD), n = 26; other iatrogenic immunodeficiency-associated LPD, n = 45) were reviewed and analyzed. The median age at diagnosis was 63 years (range, 3–83). Diffuse large B cell lymphoma was the most common subtype (n = 33), followed by Hodgkin lymphoma (n = 12), B cell monomorphic LPD not specified (n = 11), and polymorphic LPD or early-phase diseases (n = 15). The median follow-up period for survivors was 2.5 years and overall survival (OS) and progression-free survival (PFS) at 2.5 years were 75% and 67%, respectively. Multivariate analysis showed that lymphopenia (≤ 800/μL) at diagnosis predicted inferior OS (HR, 3.72; P = 0.043) and PFS (HR, 3.82; P = 0.012). Serum albumin values also strongly affected OS (> 3.18 g/dL vs. ≤ 3.18 g/dL; HR, 0.21; P = 0.010) and PFS (HR, 0.26; P = 0.013). Lymphopenia at diagnosis is suggested to predict inferior OS and PFS in patients with immunodeficiency-associated LPDs. Immunocompromised status might affect disease progression in these distinct lymphoid neoplasms growing under immunocompromised backgrounds

Next‐generation sequencing in two cases of de novo acute basophilic leukaemia

Acute basophilic leukaemia (ABL) is a rare subtype of acute myeloid leukaemia (AML); therefore, few data are available about its biology. Herein, we analysed two ABL patients using flow cytometry and next-generation sequencing (NGS). Two cell populations were detected by flow cytometry in both patients. In Case no. 1, blasts (CD34⁺, CD203c⁻, CD117⁺, CD123dim⁺) and basophils (CD34⁻, CD203c⁺, CD117±, CD123⁺) were identified, both of which were found by NGS to harbour the 17p deletion and have loss of heterozygosity of TP53. In Case no. 2, blasts (CD33⁺, CD34⁺, CD123⁻) and basophils (CD33⁺, CD34⁺, CD123⁺) were identified. NGS detected NPM1 mutations in either blasts or basophils, and TET2 in both. These data suggest an overlap of the mutational landscape of ABL and AML, including TP53 and TET2 mutations. Moreover, additional mutations or epigenetic factors may contribute for the differentiation into basophilic blasts

Intramuscular Adipose Tissue Content Predicts Patient Outcomes after Allogeneic Hematopoietic Stem Cell Transplantation

移植の成功に重要なのは、「質の良い」筋肉 --コンピュータ断層撮影を用いて評価した骨格筋指標での検討--. 京都大学プレスリリース. 2022-07-12.During clinical courses involving allogeneic hematopoietic stem cell transplantation (allo-HSCT), multidisciplinary assessments for patients including physical functions are indispensable, and quantitative skeletal muscle loss is a poor prognostic marker. In addition, deteriorating quality of muscle due to intra-muscle adipose tissue degeneration can be important as well, because many patients are cachexic or sarcopenic before allo-HSCT, although this approach has not been employed yet. Therefore, we conducted a retrospective cohort study to evaluate the quality, as well as quantity of skeletal muscle using computed tomography (CT). Psoas muscle mass index (PMI) and radiographic density (RD) calculated by cross-sectional area and averaged CT values of the psoas major muscle at the umbilical level were used to determine the quantity and quality of muscle, respectively. In total, 186 adult patients, aged 17-68 years (median, 49) were included in this study, and 46 (24.7%) and 49 (26.3%) patients were assigned to the lower PMI and RG groups. Low RD was identified as an independent risk factor for poor overall survival after allo-HSCT (adjusted hazard ratio 2.54, p<0.01), while PMI was not significant. Decreased RD along with reduced 6-min walking distance before transplantation was also significant factor for increased non-relapse mortality (hazard ratio, 2.69, p=0.01). This study is the first to suggest the use of a qualitative skeletal muscle index to serve as a prognostic indicator following allo-HSCT. RD should be included in pre-transplant screening parameters, and approaches that include rehabilitation focused on improving both muscle quality and quantity may improve the prognosis of allo-HSCT

Higher exercise tolerance early after allogeneic hematopoietic stem cell transplantation is the predictive marker for higher probability of later social reintegration

同種造血幹細胞移植後における社会復帰の予測因子を発見 --移植後リハビリテーションがもつ重要性--. 京都大学プレスリリース. 2021-04-09.As the proportion of long-term survivors after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is on the rise, it is essential to consider the significance of quality of life (QOL), including reintegration with society (returning to school or work). This retrospective cohort study aims to illustrate the precise epidemiology of social reintegration later after allo-HSCT and determine its predictive indicators. We enrolled 56 patients, and 40 patients (71%) attained social reintegration at 2 years post-HSCT. Reintegration failure markedly correlated with an inferior performance status and concurrent chronic graft-versus-host disease. In non-reintegrated patients, the physical function at discharge measured by the 6-min walking distance (6MWD) was markedly decreased. On the multivariate risk analyses, sex (female; odds ratio (OR) 0.07; 95% confidence interval (CI) 0.01–0.54; p = 0.01), HCT-CI (≥ 2; OR 0.10; 95% CI 0.01–0.84; p = 0.03), and change in 6MWD (per 5% increase; OR 1.47; 95% CI 1.01–2.13; p = 0.04) were significant predictors of later social reintegration. This study suggests that a multidisciplinary strategy including rehabilitation is essential, especially in patients with poor predictive markers at an early phase, and we should consider suitable rehabilitation programs to prevent a decline in exercise tolerance and improve social reintegration and overall QOL in patients after allo-HSCT

Personalized prediction of overall survival in patients with AML in non‐complete remission undergoing allo‐HCT

Allogenic hematopoietic stem cell transplantation (allo-HCT) is the standard treatment for acute myeloid leukemia (AML) in non-complete remission (non-CR); however, the prognosis is inconsistent. This study aimed to develop and validate nomograms and a web application to predict the overall survival (OS) of patients with non-CR AML undergoing allo-HCT (cord blood transplantation [CBT], bone marrow transplantation [BMT], and peripheral blood stem cell transplantation [PBSCT]). Data from 3052 patients were analyzed to construct and validate the prognostic models. The common significant prognostic factors among patients undergoing allo-HCT were age, performance status, percentage of peripheral blasts, cytogenetic risk, chemotherapy response, and number of transplantations. The conditioning regimen was a significant prognostic factor only in patients undergoing CBT. Compared with cyclophosphamide/total body irradiation, a conditioning regimen of ≥3 drugs, including fludarabine, with CBT exhibited the lowest hazard ratio for mortality (0.384; 95% CI, 0.266-0.554; p < 0.0001). A conditioning regimen of ≥3 drugs with CBT also showed the best leukemia-free survival among all conditioning regimens. Based on the results of the multivariable analysis, we developed prognostic models showing adequate calibration and discrimination (the c-indices for CBT, BMT, and PBSCT were 0.648, 0.600, and 0.658, respectively). Our prognostic models can help in assessing individual risks and designing future clinical studies. Furthermore, our study indicates the effectiveness of multi-drug conditioning regimens in patients undergoing CBT

Adult patients with Ph+ ALL benefit from conditioning regimen of medium‐dose VP16 plus CY/TBI

The medium-dose etoposide (VP16) added on cyclophosphamide (CY)/total body irradiation (TBI) is one of the intensified myeloablative conditioning regimens used in allogenic hematopoietic stem cell transplantation (allo-HSCT) for acute lymphoblastic leukemia (ALL). However, the patient subgroups who can actually benefit from VP16/CY/TBI compared to CY/TBI have not been precisely defined. Therefore, we conducted a multi-center retrospective study using the Japanese nationwide registry database to elucidate the efficacy of VP16/CY/TBI on post-transplant prognosis. Biological and clinical distinct subtypes (i.e., Philadelphia chromosome-positive (Ph+) and -negative (Ph−) ALL) were evaluated separately, which included 820 Ph+ and 1463 patients with Ph− ALL, respectively. Compared with the CY/TBI group, the VP16/CY/TBI group showed superior progression-free survival (PFS) in patients with Ph+ ALL (65% vs. 57% at 3 years after HSCT; adjusted hazard ratio (HR), 0.73; 95% confidence interval (CI), 0.55–0.98; p = 0.03), along with significantly reduced incidence of relapse (adjusted HR, 0.58; 95% CI, 0.37–0.90; p = 0.02) without the increase of non-relapse mortality (NRM). By contrast, in patients with Ph− ALL, VP16/CY/TBI did not improve PFS nor incidence of relapse; addition of VP16 reduced relapse (HR, 0.65; p = 0.06) in patients with Ph− ALL transplanted at CR1, while improved PFS was not observed (HR, 0.90; p = 0.52) due to increased NRM. This study demonstrated that VP16/CY/TBI is a more effective and well-tolerated regimen in comparison with CY/TBI in patients with myeloablative allo-HSCT for adult Ph+ ALL. Our findings can provide a novel algorithm for conditioning regimen selection in patients with adult ALL

Prognostic impact of complex and/or monosomal karyotypes in post‐transplant poor cytogenetic acute myeloid leukaemia: A quantitative approach

To evaluate the prognostic impact of complex karyotype (CK) and/or monosomal karyotype (MK) in combination with various clinical factors on allogeneic stem cell transplantation (HSCT) outcomes of patients with acute myeloid leukaemia (AML), we analysed the registry database of adult AML patients who underwent allogeneic HSCT between 2000 and 2019 in Japan. Among 16 094 patients, those with poor cytogenetic risk (N = 3345) showed poor overall survival (OS) after HSCT (25.3% at 5 years). Multivariate analyses revealed that CK and/or MK (hazard ratio [HR], 1.31 for CK without MK; 1.27 for MK without CK; and 1.73 for both), age at HSCT ≥50 years (HR, 1.58), male sex (HR, 1.40), performance status ≥2 (HR, 1.89), HCT-CI score ≥3 (HR, 1.23), non-remission status at HSCT (HR, 2.49), and time from diagnosis to HSCT ≥3 months (HR, 1.24) independently reduced post-HSCT OS among patients with poor cytogenetic risk AML. A risk scoring system based on the multivariate analysis successfully stratified patients into five distinct groups for OS. This study confirms the negative effects of CK and MK on post-HSCT outcomes, and offers a powerful risk scoring system for predicting prognoses after HSCT among AML patients with unfavourable cytogenetics