Comparison of Melphalan Dose in Patients with Myelodysplastic Syndrome Undergoing Allogeneic Transplantation with Reduced-Intensity Conditioning.

The present study compared lower-dose melphalan (80 mg/m2, FM80) and higher-dose melphalan (140 mg/m2, FM140) when administering reduced-intensity conditioning with fludarabine in adult patients with myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively analyzed nationwide registry data (2006 to 2019) and compared transplant outcomes between the 2 groups. Ninety-two patients (median age, 61 [interquartile range, 56 to 65] years) were assigned to the FM80 and FM140 groups by propensity score matching. The 3-year overall survival (OS) rate in the FM140 group (63.9%; 95% confidence interval [CI], 52.9% to 73.0%) was significantly higher than that in the FM80 group (54.2%; 95% CI, 37.1% to 52.1%) (P = .038). The FM140 group had a nonsignificantly (P = .095) lower 3-year cumulative incidence of relapse (15.5%; 95% CI, 8.9% to 23.8% versus 26.0%; 95% CI, 17.3% to 35.5%). The 3-year cumulative incidences of nonrelapse mortality were 22.3% (95% CI, 14.1% to 31.8%) and 23.7% (95% CI, 15.4% to 33.2%) in the FM80 and FM140 groups, respectively (P = .49). The beneficial effect of FM140 was more evident in patients with a poor cytogenetic risk. Our findings suggest the superiority of FM140 in patients with MDS undergoing allo-HSCT, especially in high-risk patients.

Updated comparable efficacy of cord blood transplantation for chronic myelomonocytic leukaemia: a nationwide study.

Chronic myelomonocytic leukaemia (CMML) is a haematological malignancy with a poor prognosis. Allogeneic haematopoietic stem cell transplantation remains the only curative approach. Without human leucocyte antigen-matched related sibling donors, the optimal alternative donor has yet to be established. Although unrelated bone marrow transplantation (UBMT) has been extensively studied, cord blood transplantation (CBT) for CMML remains largely unexplored. This nationwide retrospective study compared the outcomes of UBMT and single-unit umbilical CBT in patients with CMML. This study included 118 patients who underwent their first allo-HSCT during 2013-2021. Of these, 50 received BMT (UBMT group), while 68 underwent CBT (CBT group). The primary endpoint was the 3-year overall survival (OS). There were comparable 3-year OS rates between the UBMT (51.0%, 95% confidence interval [CI]: 34.1-65.5%) and CBT (46.2%, 95% CI: 33.2-58.1%; P = 0.60) groups. In the inverse probability of treatment weighting analysis, CBT did not show significantly improved outcomes compared with UBMT regarding the 3-year OS rate (hazard ratio 0.97 [95% CI: 0.57-1.66], P = 0.91). Thus, CBT may serve as an alternative to UBMT for patients with CMML. Further research is necessary to optimise transplantation strategies and enhance outcomes in patients with CMML undergoing CBT.

[Kidney transplantation for end-stage renal disease after third allogeneic hematopoietic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia].

An 18-year-old man underwent allogenic bone marrow transplantation (BMT) for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). Ph+ALL relapsed 3 months after the first BMT, and the patient underwent a second BMT. However, Ph+ALL relapsed 4 months after the second BMT, and he received a haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) from his father. Molecular complete remission was confirmed 29 days after haplo-PBSCT. However, the patient needed dialysis for end-stage renal disease due to thrombotic microangiopathy 3 years and 2 months after haplo-PBSCT. He received a kidney transplantation from his father 7 years and 10 months after haplo-PBSCT, and got off dialysis after the kidney transplantation. Immunosuppressive therapy with methylprednisolone, tacrolimus, and mycophenolate mofetil was started for kidney transplantation, but the dose of immunosuppressive agents was reduced successfully without rejection soon after kidney transplantation. The patient has maintained long-term remission since the haplo-PBSCT, and his kidney function was restored by the kidney transplantation from his father.

The prognosis and risk factors for patients with complex karyotype myelodysplastic syndrome undergoing allogeneic haematopoietic stem cell transplantation.

Allogeneic haematopoietic stem cell transplantation (HCT) is the curative treatment for myelodysplastic syndrome with a complex karyotype (CK-MDS). However, only a few studies have been limited to patients with CK-MDS undergoing allogeneic HCT. This study aimed to identify the risk factors for patients with CK-MDS undergoing allogeneic HCT. We included 691 patients with CK-MDS who received their first allogeneic HCT. The overall survival (OS) was the primary end-point, estimated using the Kaplan-Meier method. Prognostic factors were identified using a Cox proportional hazards model. The 3-year OS was 29.8% (95% confidence interval [CI]: 26.3-33.3). In the multivariable analysis, older age (hazard ratio [HR]: 1.44, 95% CI: 1.11-1.88), male sex (HR: 1.38, 95% CI: 1.11-1.71), poor haematopoietic cell transplant comorbidity index (HR: 1.47, 95% CI: 1.20-1.81), red blood cell transfusion requirement (HR: 1.58, 95% CI: 1.13-2.20), platelet transfusion requirement (HR: 1.85, 95% CI: 1.46-2.35), not-complete remission (HR: 1.55, 95% CI: 1.16-2.06), a high number of karyotype abnormality (HR: 1.63, 95% CI: 1.18-2.25) and monosomal karyotype (HR: 1.49, 95% CI: 1.05-2.12) were significantly associated with OS. Thus, the 3-year OS of allogeneic HCT was 29.8% in patients with CK-MDS, and we identified risk factors associated with poor OS.

Evaluation of the cachexia index using a bioelectrical impedance analysis in elderly patients with non-Hodgkin's lymphoma: A single-center prospective study.

Cancer cachexia is a disorder that affects patient outcomes. The present study prospectively evaluated the prognostic value of the cachexia index (CXI) in elderly patients with non-Hodgkin's lymphoma (NHL). We prospectively analyzed 51 elderly patients who were diagnosed with NHL at our institution. CXI was calculated as follows: CXI = SMI × Alb/NLR (SMI: skeletal muscle index, Alb: serum albumin, NLR: neutrophil-to-lymphocyte ratio). SMI was measured by a bioelectrical impedance analysis (BIA) using the InBody 720. We determined the sex-specific cutoff values of the CXI by a receiver operating characteristic curve analysis and divided all patients into low- and high-CXI groups. The median age at the diagnosis was 78 years (60-93 years), and 28 (55%) were male. The histologic subtypes were B-cell lymphoma in 49 patients and T-cell lymphoma in 2. Twenty-eight (55%) patients were categorized into the high-CXI group, and 23 (45%) were categorized into the low-CXI group. The overall survival (OS) in the low-CXI group was significantly shorter than that in the high-CXI group (3-year OS, 70.4% vs. 95.7%, p = 0.007). Among 23 patients with DLBCL, patients with low-CXI had shorter OS than those with high-CXI (3-year OS, 55.6% vs. 92.9%, p = 0.008). On the other hand, sarcopenia had less impact on the clinical outcome of DLBCL patients. Low-CXI was associated with poor outcomes in elderly NHL and the CXI may be a clinical useful index for predicting prognosis. Further large prospective studies are needed to verify this conclusion.

Identifying the optimal conditioning intensity for stem cell transplantation in patients with myelodysplastic syndrome: a machine learning analysis.

A conditioning regimen is an essential prerequisite of allogeneic hematopoietic stem cell transplantation for patients with myelodysplastic syndrome (MDS). However, the optimal conditioning intensity for a patient may be difficult to establish. This study aimed to identify optimal conditioning intensity (reduced-intensity conditioning regimen [RIC] or myeloablative conditioning regimen [MAC]) for patients with MDS. Overall, 2567 patients with MDS who received their first HCT between 2009 and 2019 were retrospectively analyzed. They were divided into a training cohort and a validation cohort. Using a machine learning-based model, we developed a benefit score for RIC in the training cohort. The validation cohort was divided into a high-score and a low-score group, based on the median benefit score. The endpoint was progression-free survival (PFS). The benefit score for RIC was developed from nine baseline variables in the training cohort. In the validation cohort, the hazard ratios of the PFS in the RIC group compared to the MAC group were 0.65 (95% confidence interval [CI]: 0.48-0.90, P = 0.009) in the high-score group and 1.36 (95% CI: 1.06-1.75, P = 0.017) in the low-score group (P for interaction < 0.001). Machine-learning-based scoring can be useful for the identification of optimal conditioning regimens for patients with MDS.

Central nervous system mucormycosis in a patient with hematological malignancy: A case report and review of the literature.

Invasive mucormycosis is a refractory fungal infection. Central nervous system (CNS) mucormycosis is a rare complication caused by infiltration from the paranasal sinuses or hematogenous dissemination. Here, we present a case of a brain abscess, due to mucormycosis, diagnosed using burr craniotomy. A 25-year-old Japanese woman with relapsed-refractory acute lymphoblastic leukemia underwent cord blood transplantation (CBT). The patient experienced prolonged and profound neutropenia, and oral voriconazole was administered as primary antifungal prophylaxis. The patient received a conditioning regimen on day -11 and complained of aphasia and right hemiparesis on day -6. Magnetic resonance imaging (MRI) revealed a T2-weighted high-intensity area in the left frontal cortex. A brain abscess was suspected, and liposomal amphotericin B (L-AMB) administration was started. The patient underwent CBT as scheduled and underwent neutrophil engraftment on day 14. Although the patient achieved complete remission on day 28, her consciousness level gradually deteriorated. MRI revealed an enlarged brain lesion with a midline shift sign, suggesting brain herniation. Craniotomy was performed to relieve intracranial pressure and drain the abscess on day 38, and a diagnosis of cerebral mucormycosis was confirmed. The L-AMB dose was increased to 10 mg/kg on day 43. Although the patient's consciousness level improved, she died of hemorrhagic cystitis and aspiration pneumonia. Cerebral mucormycosis should be suspected if neurological symptoms are observed in stem cell transplant recipients. Prompt commencement of antifungal therapy and debridement are crucial because mucormycosis has a poor prognosis.

[Late-onset refractory autoimmune hemolytic anemia following autologous hematologic recovery after allo-HSCT in aplastic anemia-PNH syndrome].

A 31-year-old man underwent allogeneic bone marrow transplantation (BMT) for the treatment of transfusion-dependent aplastic anemia (AA) after conditioning with a regimen including fludarabine, cyclophosphamide, and antithymocyte globulin. The patient developed a late graft rejection on day 103 and showed autologous hematologic recovery not requiring transfusions on day 76. Peripheral blood leukocytes were of 100% recipient origin on day 103, and paroxysmal nocturnal hematuria (PNH)-type granulocytes were detected 5 months after BMT. The patient suddenly experienced hemolytic symptoms triggered by cold stimulation, and was diagnosed with autoimmune hemolytic anemia (AIHA) 37 months after BMT. Although anemia was ameliorated by prednisolone (PSL), hemolytic attacks repeatedly occurred, which became refractory to corticosteroids. Moreover, the patient underwent a splenectomy for the steroid-resistant AIHA and achieved AIHA remission without the need for PSL at 53 months after BMT. The immune tolerance breakdown to erythrocyte antigens was thought to have occurred due to various factors including immune AA, medication, cold stimulation, and infection, leading to AIHA development in this case.

Allogeneic Hematopoietic Stem Cell Transplantation for Adult Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia in Second Complete Remission.

Even in the era of high-intensity chemotherapy, disease recurrence remains a major cause of treatment failure in adult patients with Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia (Ph-negative B-ALL). For patients who achieved second complete remission (CR2) with salvage chemotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) could be the best curative treatment. However, limited data are available on the outcomes of allo-HSCT for adult Ph-negative B-ALL in CR2 in the high-intensity chemotherapy era. We evaluated the transplantation outcomes of adult patients with Ph-negative B-ALL in CR2 compared with those in CR1. We also clarified the prognostic factors among adult allo-HSCT recipients with Ph-negative B-ALL in CR2. We conducted a nationwide retrospective study using the data form Japanese transplant registry database. Patients aged ≥16 years and underwent their first allo-HSCT between 2003 and 2017 were included. The 3-year overall survival (OS) rate of the patients in CR2 (n = 382) was significantly lower than that in first complete remission (n = 1375) (51.8% versus 68.1%; P < .001), accompanied by a higher relapse rate (34.2% versus 17.6% at 3 years; P < .001). In a multivariate analysis among CR2 patients, time from diagnosis to allo-HSCT (≤2 years) was a significant factor for OS (hazard ratio [HR] 1.87; P < .001) and relapse (HR = 1.88; P < .001), whereas age at allo-HSCT (≥30 years) was a significant factor for OS (HR = 2.10, P < .001) and nonrelapse mortality (HR = 2.68; P < .001). By assigning a score of 1 to each factor, the 3-year OS rate of CR2 patients significantly stratified: 70.7% in patients with score 0, 56.4% with score 1, and 28.4% with score 2 (P < .001). The survival outcomes of allo-HSCT in adult Ph-negative B-ALL patients in CR2 were inferior to those in CR1 in the high-intensity chemotherapy era, mainly because of the higher relapse rate. Among the CR2 patients, the short time between diagnosis and allo-HSCT was a significant risk factor for disease recurrence and overall mortality. Better disease control with novel treatment strategies may be needed for early relapse. In addition, the nonrelapse mortality rate in patients over 30 years of age was particularly high among CR2 patients, suggesting the need for improved supportive care for these patients. Further studies are warranted on the outcomes of allo-HSCT after achieving CR2 with novel drugs, such as inotuzumab ozogamicin and blinatumomab.

Myeloablative Versus Reduced-Intensity Conditioning With Fludarabine/Busulfan for Myelodysplastic Syndrome: A Propensity Score-Matched Analysis.

There are limited data comparing myeloablative conditioning with fludarabine/busulfan (Flu/Bu4) and reduced-intensity conditioning with fludarabine/busulfan (Flu/Bu2) in patients with myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively analyzed nationwide registry data and compared the outcomes of adult patients with MDS receiving Flu/Bu4 and Flu/Bu2 by propensity score (PS) matching. Patients who met the following criteria were eligible for enrollment: (1) age ≥16 years; (2) diagnosis of de novo MDS; (3) first allo-HSCT between 2006 and 2018; (4) related bone marrow transplantation (BMT) or peripheral blood stem cell transplantation from an HLA-matched donor, unrelated BMT from an HLA-matched or HLA-1 allele-mismatched donor, or unrelated cord blood transplantation; and (5) receiving Flu/Bu4 or Flu/Bu2 as a conditioning regimen. Flu/Bu4 comprised intravenous busulfan (total dose, 12.8 mg/kg) combined with fludarabine (total dose, 125-180 mg/m2). Flu/Bu2 comprised intravenous busulfan (total dose, 6.4 mg/kg) combined with the same dose of fludarabine. To minimize selection bias and confounding factors, we performed a propensity score (PS)-matched analysis. The primary endpoint was overall survival (OS) after allo-HSCT. A total of 3386 patients with de novo MDS underwent their first allo-HSCT between 2006 and 2018. Among them, 202 patients were assigned each to the Flu/Bu4 and Flu/Bu2 groups after PS-matched analysis. The median age was 61 (interquartile, 57-65) years. The 3-year OS rates were 44.8% (95% confidence interval [CI], 37.1-52.1%) and 46.9% (95% CI, 39.2-54.2%) in the Flu/Bu4 and Flu/Bu2 groups, respectively (P = .67). The 3-year rates of graft-versus-host disease (GVHD)-free survival, relapse-free survival (GRFS) were 28.8% (95% CI, 22.2-35.7%) and 33.0% (95% CI, 26.2-40.0%), respectively (P = .36). The 3-year cumulative incidence rates of relapse were 28.9% (95% CI, 22.6-35.6%) and 30.0% (95% CI, 23.6-36.6%), respectively (P = .47). The 3-year cumulative incidence rates of non-relapse mortality (NRM) were 28.2% (95% CI, 21.7-35.0%) and 27.1% (95% CI, 20.6-33.9%), respectively (P = .60). The 100-day cumulative incidence rate of grade II-IV acute GVHD was significantly higher in the Flu/Bu4 group than in the Flu/Bu2 group (41.7% [95% CI, 34.8%-48.4%] versus 29.3% [95% CI, 23.2%-35.7%], P = 0.012). To identify patients who had more favorable outcomes with 1 of the 2 regimens, we compared the outcomes between the 2 groups after stratifying by age, hematopoietic cell transplantation-comorbidity index, cytogenetic risk, disease status at allo-HSCT, stem cell source, and donor type. OS, GRFS, relapse, and NRM did not differ between the 2 groups in any subgroup analyses. There were no significant interactions between the choice of conditioning regimens and any other factors. There are no differences in survival between Flu/Bu4 and Flu/Bu2, although our study population was highly selected by PS matching. Data from more patients and prospective studies are needed to determine the optimal intensity of conditioning regimens in patients with MDS.

Fludarabine/busulfan versus busulfan/cyclophosphamide as myeloablative conditioning for myelodysplastic syndrome: a propensity score-matched analysis.

Myeloablative conditioning with fludarabine/busulfan (Flu/Bu4) prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT) is effective for acute myeloid leukemia. However, the effectiveness of Flu/Bu4 for myelodysplastic syndrome (MDS) remains poorly understood. Therefore, we retrospectively analyzed nationwide registry data in Japan from 2006 to 2018 and compared transplant outcomes of adult MDS patients receiving Flu/Bu4 and busulfan/cyclophosphamide (Bu4/Cy) using propensity score (PS) matching. The primary endpoint was overall survival (OS). Among 2,482 MDS patients, 153 patients were assigned each to the Flu/Bu4 and Bu4/Cy groups. The 3-year OS rates were 52.7% (95% confidence interval [CI], 43.8-60.8%) and 49.5% (95% CI, 40.8-57.6%) in the Flu/Bu4 and Bu4/Cy group, respectively (P = 0.548). The 3-year progression-free survival (P = 0.858), the cumulative incidence of relapse (P = 0.536), and cumulative incidence of non-relapse mortality (P = 0.684) were not significantly different between the two groups. According to the findings of subgroup analyses, no patient had a favorable OS when using either of the two regimens. In conclusion, although our PS-matched cohort mainly comprised older patients who had a low hematopoietic cell transplantation-comorbidity index and low-risk disease status, Flu/Bu4 could be an alternative to Bu4/Cy for MDS patients prior to allo-HSCT.

Syngeneic hematopoietic stem cell transplantation for acute myeloid leukemia: a propensity score-matched analysis.

The present study evaluated outcomes and prognostic factors in adult patients with acute myeloid leukemia (AML) after syngeneic hematopoietic stem cell transplantation (HSCT). Among patients in first complete remission (CR1), outcomes of syngeneic HSCT (Syn) were compared with those of autologous HSCT (Auto), allogeneic HSCT from human leukocyte antigen (HLA)-matched sibling donor (MSD), or allogeneic HSCT from HLA-matched unrelated donor (MUD). Among 11,866 patients receiving first HSCT, 26 in the Syn group were analyzed. The 5-year overall survival (OS) rate, the cumulative incidence of relapse, and the cumulative incidence of non-relapse mortality (NRM) were 47.8%, 59.6%, and 4.6%, respectively. The OS was significantly better in patients in CR1 (n = 13) than in patients in non-CR1 (P = 0.012). Furthermore, 39 patients in CR1 each were assigned to the Auto, MSD, and MUD groups using propensity score matching. The 5-year OS in the Syn (68.4%) was not significantly different from those in the Auto (55.9%, P = 0.265), MSD (62.4%, P = 0.419), or MUD (63.7%, P = 0.409) groups. A higher relapse in the Syn than in the MSD and MUD groups was offset by lower NRM. In summary, syngeneic HSCT might be an alternative option for AML patients in CR1.

Outcome of allogeneic hematopoietic stem cell transplantation for T-cell lymphoblastic leukemia/lymphoma: A single-center study.

Although the indications for allogeneic hematopoietic stem cell transplantation (allo-HSCT) as a treatment for T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) and Philadelphia chromosome (Ph)-negative B-cell acute lymphoblastic leukemia (B-ALL) are similar, few studies have compared its outcomes for T-ALL/LBL and Ph-negative B-ALL. The clinical data of 28 patients with T-ALL, 16 with T-LBL, and 99 with Ph-negative B-ALL who underwent the first allo-HSCT from 2000 to 2019 were retrospectively analyzed. Complete remission (CR) rates at allo-HSCT were 79 %, 63 %, and 75 % for T-ALL, T-LBL, and B-ALL, respectively; the 3-year overall survival (OS) rates were 55.7 %, 56.2 %, and 58.6 %, respectively (p = 0.92). Univariate analysis revealed that disease subtypes were not significantly associated with OS (B-ALL vs. T-ALL: hazard ratio [HR]=0.89, p = 0.70; T-LBL vs. T-ALL: HR=0.87, p = 0.75), and CR at allo-HSCT was the only prognostic factor for OS (HR=0.25, p < 0.001). Multivariate analysis demonstrated that CR at allo-HSCT was the only predictor of OS (HR=0.24, p < 0.001). In all three disease subtypes, patients in CR at allo-HSCT tended to have a lower cumulative incidence of relapse than did those in non-CR (T-ALL: 13.6 % vs. 50.0 %, p = 0.10; T-LBL: 20.0 % vs. 50.0 %, p = 0.21; B-ALL: 10.0 % vs. 56.0 %, p < 0.01). Thus, the outcomes of allo-HSCT for T-ALL/LBL were comparable to those of Ph-negative B-ALL. Irrespective of the disease subtypes, achieving CR before allo-HSCT was associated with a favorable OS. Further advances in chemotherapy before allo-HSCT and defining the optimal timing of allo-HSCT would improve the prognosis of patients with T-ALL/LBL.

Allogeneic hematopoietic stem cell transplantation for adult patients with B-cell acute lymphoblastic leukemia with high hyperdiploidy: a retrospective nationwide study.

We compared the transplant outcomes of adult patients with B-cell acute lymphoblastic leukemia characterized by high hyperdiploidy (HeH; 51-65 chromosomes) (n = 29) and those with a normal karyotype (n = 87) by propensity score-matched analysis. There were no significant differences among groups in 3-year probabilities of overall survival (OS, 63.5% vs. 55.3%, p = .553), cumulative relapse incidence (28.6% vs. 28.7%, p = .982), and non-relapse mortality (10.9% vs. 21.4%, p = .303). Three-year OS was significantly worse in HeH patients with third or later complete remission (CR) or non-CR compared with those in first CR (19.0% vs. 69.9%, p = .010). Frequently gained chromosomes +21 (75.9%), +4 (69.0%), +6 (69.0%), +10 (69.0%), and +1 (69.0%) had no significant prognostic impact on the OS of patients with HeH in multivariate analyses. Patients with HeH who may benefit from allogeneic hematopoietic stem cell transplantation should be further analyzed.

Mutation profiles of diffuse large B-cell lymphoma transformation of splenic B-cell lymphoma/leukemia, unclassifiable on whole-exome sequencing.

A 58-year-old male was diagnosed with splenic B-cell lymphoma/leukemia, unclassifiable (SPLL-U). The lymphoma transformed into diffuse large B-cell lymphoma (DLBCL), and multidrug chemotherapy and autologous stem cell transplantation achieved complete remission. Two years later, the lymphoma relapsed as SPLL-U. Serial whole-exome sequencing indicated that the mutation profiles were similar between the onset and relapsed samples while those in DLBCL were partially distinctive, which was in line with the clinical course. Hierarchical clustering revealed that an IGLL5 mutation was the founder mutation proceeding the development of the diseases and suggested that KRAS and other mutations might contribute to the transformation.

Aging and leukemic evolution of hematopoietic stem cells under various stress conditions.

Hematopoietic stem cells (HSCs) have self-renewal capacity and differentiation potential into all lineages of blood cells throughout the lifetime of an organism. The function of HSCs gradually changes during aging. To date, various stress factors influencing HSC aging have been identified. The increased production of reactive oxygen species and DNA damage responses are causatively attributed to HSC aging. The increased apolarity is a prominent feature of aged HSCs, whereas it is less obvious in young HSCs. The bone marrow (BM) microenvironment niche is a crucial factor for HSC aging. Mesenchymal stem cells show skewed differentiation during aging, which leads to decreased bone formation and increased adipogenesis. The accumulation of adipocytes confers negative effects on hematopoiesis. Loss of sympathetic nerve fibers or adrenoreceptor ß3 signaling induces premature HSC and niche aging. Epigenetic regulators such as polycomb group proteins and the sirtuin family of proteins act to prevent premature aging. Targeting these factors, several rejuvenation strategies for aged HSCs have been employed in mice. However, we still do not know whether these strategies can be extrapolated to human HSCs. Aging is frequently accompanied by the development of clonal hematopoiesis, which is called age-related clonal hematopoiesis (ARCH) or clonal hematopoiesis of indeterminate potential (CHIP). Most ARCH/CHIP mutations occur in genes encoding epigenetic regulators including DNMT3A, TET2, and ASXL1, which suggests the relevance of epigenetic drift during the aging process. ARCH/CHIP is a strong risk factor for subsequent hematologic cancer. Notably, it also has an impact on the development of non-malignant disorders such as coronary heart disease. Further studies are warranted to decipher the complete picture of molecular crosstalk that regulates HSC aging.

Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Myelodysplastic/Myeloproliferative Neoplasms-Unclassifiable: A Retrospective Nationwide Study of the Japan Society for Hematopoietic Cell Transplantation.

To date, there are no data focusing on outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myelodysplastic/myeloproliferative neoplasms, unclassifiable (MDS/MPN-U). This study aimed to evaluate outcomes and prognostic factors in patients with MDS/MPN-U after allo-HSCT using Japanese nationwide registry data. The primary endpoint was 3-year overall survival (OS); secondary endpoints included the cumulative incidence of relapse and nonrelapse mortality (NRM). We evaluated the prognostic factors for 3-year OS by univariate analysis using the log-rank test. In our cohort of 86 patients with MDS/MPN-U, we found a 3-year OS of 48.5%, cumulative incidence of relapse of 23.7%, and NRM of 26.3%. The 3-year OS was significantly worse in patients age ≥50 years compared with those age <50 years (38.1% versus 65.0%; P = .049) and in patients with disease progression compared with those without disease progression (28.4% versus 57.2%; P = .042). Our results suggest that allo-HSCT may offer a curative option for patients with MDS/MPN-U, and that age and disease status could be important indicators in helping clinicians determine treatment options for these patients.