Prognostic implication of CTLA-4, PD-1, and PD-L1 expression in aggressive adult T-cell leukemia-lymphoma.

The prognosis of patients with aggressive adult T cell leukemia-lymphoma (ATLL) is dismal even with intensive chemotherapy. Allogeneic hematopoietic stem cell transplantation (HSCT) is a promising option for patients with aggressive ATLL, but the posttransplant outcome remains unsatisfactory. Hence, to further improve clinical outcomes, novel therapeutic approaches are needed. The clinical significance of immune checkpoint protein expression has not been well-established in aggressive ATLL. This study aims to identify the association between the expression profile of immune checkpoint proteins on ATLL cells and clinical outcomes. This retrospective study cohort included 65 patients with aggressive ATLL diagnosed between 2001 and 2015 at the National Cancer Center Hospital, Tokyo, Japan. Formalin-fixed paraffin-embedded tissue was used to immunohistochemically determine the expression of immune checkpoint proteins and assess the impact of expression profile on the probability of overall survival from diagnosis or HSCT. The current analysis shows that cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1), and programmed death-ligand 1 (PD-L1) expressions were adverse prognostic factors in patients with aggressive ATLL. Experiments that assess the efficacy of immune checkpoint inhibitors are warranted to alleviate the adverse impacts associated with negative immune checkpoints.

The role of local radiotherapy following rituximab-containing chemotherapy in patients with transformed indolent B-cell lymphoma.

OBJECTIVES: This study aimed to evaluate the outcomes of local radiotherapy (LRT) in patients with histologic transformation (HT) following rituximab-containing chemotherapy. METHODS: We retrospectively analysed 92 patients with biopsy-confirmed HT undergoing rituximab-containing chemotherapy at our institution between 2003 and 2015. RESULTS: Of the 36 patients with limited-stage disease at diagnosis of HT, 29 (78%) received LRT. The estimated 5-year progression-free survival (PFS) rate was significantly better in patients who underwent LRT than in those who did not (93% and 42%, respectively; P < 0.05). Multivariate analyses employing age, sex, performance status, LRT and treatment response demonstrated that LRT was an independent prognostic factor for PFS (hazard ratio [HR]: 11.8; 95% confidence interval [CI]: 1.28-108.1; P < 0.05). Of the 32 patients who underwent LRT for HT lesion treatment, 31 (97%) did not show disease progression within radiation fields; among them, 27 patients (84%) survived without disease progression during the follow-up period. One patient developed hypothyroidism due to LRT; the others had no acute or late-onset complications of LRT. CONCLUSIONS: Our data support the recommendation of LRT for HT lesion treatment following rituximab-containing chemotherapy in select patients with localised HT, as a rational treatment approach with potentially limited toxicity.

Usefulness of hematopoietic progenitor cell monitoring to predict autologous peripheral blood stem cell harvest timing: A single-center retrospective study.

INTRODUCTION: In autologous peripheral blood stem cell harvest (APBSCH), CD34-positive cells have been measured to assess the numbers of hematopoietic stem cells, but measurement requires specialized equipment. Recently, there was a report that peripheral blood hematopoietic progenitor cells (HPCs) are useful indicators of the presence of hematopoietic stem cells. We examined the usefulness of HPC monitoring to predict APBSCH timing. METHODS: We retrospectively analyzed the relationship between HPC and collected CD34-positive cells in 84 consecutive patients who underwent APBSCH. RESULTS: According to the receiver operating characteristics curve for the collection of ≥2 × 106 CD34-positive cells/kg, the HPC cut-off value on the day before collection was 21/µL, while that on the day of collection was 41/µL. No significant factors were found in the univariate analysis except for the HPC count on the day before collection (p < 0.001) and the day of collection (p < 0.001). According to the multivariate analysis, the HPC count on the day before collection (p < 0.001) and the day of collection (p < 0.001) were also factors that strongly influenced the quantity of CD34-positive cells collected. CONCLUSION: Our results suggest that the HPC count on not only the day of collection but also the day before collection is a good indicator for appropriate APBSCH timing.

Association of CD204+ macrophages with poor outcomes of malignant lymphomas not in remission treated by allogeneic HCT.

OBJECTIVE: CD204+ tumor-associated macrophages are associated with adverse outcomes of various malignancies. We performed a study to elucidate the role of CD204+ macrophages in allogeneic hematopoietic cell transplantation (allogeneic HCT). METHODS: In a total of 81 patients who received allogeneic HCT for non-remission malignant lymphoma, immunohistochemical staining of CD204 using specimens preserved before allogeneic HCT was performed. According to the average number of CD204+ macrophages in a high-power field, patients were categorized into three groups: low (<25th percentile), intermediate (≥25th percentile and <50th percentile), and high (≥50th percentile). RESULTS: The B-cell lymphoma proportion was higher in the low group, while T-cell lymphoma and adult T-cell leukemia proportions were higher in the high group. The 3-year overall survival (OS) was poorest in the high group; low vs intermediate vs high = 83.3% vs 43.7% vs 20.2% (P < .01). The 3-year cumulative incidences of relapse were significantly higher in the high group than the intermediate and low groups: 67.0% vs 38.1% vs 18.2% (P < .01). In multivariate analyses, the numbers of CD204+ macrophages were independent risk factors of poorer OS and cumulative incidences of relapse. CONCLUSIONS: CD204+ macrophages might be associated with poorer prognosis in allogeneic HCT for malignant lymphomas.

Double-Expressor Lymphoma Is Associated with Poor Outcomes after Allogeneic Hematopoietic Cell Transplantation.

Double-expressor lymphoma (DEL) is a diffuse large B cell lymphoma that exhibits co-expression of MYC and BCL2 proteins by immunohistochemistry. Patients with double-expressor lymphoma have a poor prognosis after standard chemoimmunotherapy or after high-dose chemotherapy with autologous transplantation, but the prognostic impact of DEL after allogeneic hematopoietic cell transplantation has not been well characterized. We retrospectively analyzed 60 consecutive patients with de novo diffuse large B cell lymphoma or transformed follicular lymphoma who underwent allogeneic transplantation at our center and had available immunohistochemistry data. Thirty-seven patients (62%) had DEL. The 2-year progression-free and overall survival rates were lower in patients with DEL than in those without DEL (20% versus 78%; overall P <.001 and 46% versus 77%; overall P = .016, respectively). The cumulative incidence of disease progression at 2 years was higher in patients with DEL (60% versus 13%; overall P = .005). The cumulative incidence of nonrelapse mortality did not differ statistically in the 2 groups. Even in patients with DEL and chemosensitive disease at transplantation, the 2-year progression-free survival rate was only 27% due to early disease progression. Multivariate analysis showed associations between DEL and increased risks of progression-free survival events (hazard ratio [HR], 4.58; 95% confidence interval [CI], 2.07-10.2; P <.001), overall mortality (HR, 2.29; 95% CI, 1.03-5.09; P = .042) and disease progression (HR, 3.60; 95% CI, 1.38-9.44; P = .009). Patients with DEL had poor outcomes after allogeneic transplantation. Innovative strategies are needed to improve outcomes in this population.

[Japan Marrow Donor Program and its coordinating process: current situations].

We evaluated 18,487 patients and 223,842 cases of donor coordination among patients enrolled in the Japan Marrow Donor Program (JMDP) from January 2004 to December 2013. For patients who underwent stem cell transplantation from a JMDP donor [unrelated bone marrow transplantation (UBMT)], the median number of coordination and days from registration to transplantation were 11 and 146, respectively. Among enrolled patients, 40% did not undergo UBMT. With the increased estimated number of human leukocyte antigen 6/6-matched donors, the probability of undergoing UBMT was higher, and in those who underwent UBMT, the duration of coordination was shorter. Regarding the reasons for the termination of coordination, those attributable to the donors varied depending on the age and sex of the donors. Male donors in their 20s had lower and higher termination rates because of health conditions and inconvenience, respectively, compared with donors of different age and female sex. Among donors who experienced coordination more than once, the donation rate was higher if the precedent coordination ended because of reasons attributable to the patient compared with the donation rate because of other reasons. Using the results of our study, strategies to achieve a more efficient and rapid coordination process are warranted.

Clinical Utility of Wilms' Tumor 1 Monitoring in Patients with Myeloid Malignancy and Prior Allogeneic Hematopoietic Stem Cell Transplantation.

Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is 1 of the standard treatments for myeloid malignancy, relapse remains a major obstacle to cure. Early detection of relapse by monitoring of minimal residual disease (MRD) may enable us to intervene pre-emptively and potentially prevent overt relapse. Wilms' tumor 1 (WT1) is well known as a pan-leukemic marker. We retrospectively examined serially monitored WT1 levels of peripheral blood in 98 patients (84 with acute myeloid leukemia and 14 with myelodysplastic syndrome). At the time of allo-HSCT, 49 patients (50%) were in complete remission. Patients were divided into 3 groups according to WT1 levels (<50 copies/µg RNA, 50 to 500 copies/µg RNA and >500 copies/µg RNA). The cumulative incidence of relapse (CIR) and overall survival (OS) differed statistically according to the WT1 levels before allo-HSCT and at days 30 and 60 after allo-HSCT. In multivariate analysis, WT1 >500 copies/µg RNA before and at day 60 after allo-HSCT and WT1 ≥50 copies/µg RNA at day 30 were correlated with CIR. Moreover, WT1 >500 copies/µg RNA at day 60 after allo-HSCT was only correlated with worse OS. Our data suggest that serial monitoring of WT1 levels in peripheral blood may be useful for MRD monitoring and as a predictor of hematological relapse in allo-HSCT.

Prognosis of patients with peripheral T cell lymphoma who achieve complete response after CHOP/CHOP-like chemotherapy without autologous stem cell transplantation as an initial treatment.

Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)/CHOP-like chemotherapy has been mostly applied to patients with untreated peripheral T cell lymphoma (PTCL). Because the long-term outcome of patients with PTCL, especially those achieving complete response (CR), has not been fully elucidated, we retrospectively analyzed 78 consecutive patients initially treated with CHOP/CHOP-like chemotherapy, without high-dose chemotherapy followed by autologous stem cell transplantation (HDC/auto-SCT). Median overall and progression-free survivals in all 78 patients were 44 and 17 months, respectively, with a median follow-up of 62 months. In the 53 patients achieving CR, the median relapse-free survival (RFS) was 21 months, and 2-, 3-, and 5-year RFSs were 46, 45, and 36%, respectively. Although our results showed an unfavorable outcome for PTCL as a whole, those who achieved CR following CHOP/CHOP-like chemotherapy did not always have a poor outcome without the consolidation of HDC/auto-SCT; in particular, 45% of the 65 years or younger patients were alive without disease at 5 years.

Association of Cumulative Steroid Dose with Risk of Infection after Treatment for Severe Acute Graft-versus-Host Disease.

This study aimed to characterize the incidence and risk factors of invasive fungal disease, cytomegalovirus infection, other viral diseases, and gram-negative rod infection after glucocorticoid treatment for severe acute graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation and to elucidate the associations of cumulative steroid dose with the risks of individual infections. The study cohort included 91 consecutive patients who developed maximum grades III and IV acute GVHD at our center. The mean cumulative prednisolone-equivalent dose was 41 mg/kg during the first 4 weeks. The cumulative incidence rates of fungal disease, cytomegalovirus disease, other viral diseases, and gram-negative rod infection at 6 months after glucocorticoid treatment were remarkably high, at 14%, 21%, 28%, and 20%, respectively. GVHD within 26 days after transplantation and low lymphocyte count at GVHD treatment were associated with increased risks of several infections. Cumulative prednisolone-equivalent steroid doses ≥ 55 mg/kg during the first 4 weeks were associated with an increased risk of fungal disease (hazard ratio, 3.65; P = .03) and cumulative doses ≥ 23 mg/kg were associated with an increased risk of non-cytomegalovirus viral diseases (hazard ratio, 4.14; P = .02). Strategies to reduce the risk of infectious complications are needed, particularly for patients who have risk factors and those who receive high cumulative steroid doses.

Influence of the watch and wait strategy on clinical outcomes of patients with follicular lymphoma in the rituximab era.

We analyzed the effects of the initial approach to patients with follicular lymphoma (FL) on outcomes in order to investigate whether the watch and wait (WW) strategy is still an acceptable approach in the rituximab era. We retrospectively analyzed 348 patients who were initially diagnosed with FL between 2000 and 2012. We compared the clinical outcomes of the WW cohort and immediate treatment cohort. Among 348 patients (median age of 57 years, range: 19-85), 101 were initially managed with WW and 247 were immediately treated. The median follow-up duration was 75 months (range: 7-169). The estimated median time to treatment failure (TTF) in the treatment following WW cohort and immediate treatment cohort were 92 months (95 % CI, 60.1-NA) and 77 months (95 % CI, 65.1-107.6), respectively, which were not significantly different (P = 0.272) . In a multivariate analysis, clinical stage was identified as a predictive factor of TTF (HR 1.19, 95 % CI, 1.03-1.38, P < 0.05). Neither overall survival rate nor cumulative risk of transformation between the WW cohort and immediate treatment cohort was significant. The results of the present study suggested that the WW strategy is still an acceptable approach for selected FL patients in the rituximab era.

Positive impact of chronic graft-versus-host disease on the outcome of patients with de novo myelodysplastic syndrome after allogeneic hematopoietic cell transplantation: a single-center analysis of 115 patients.

To evaluate the impact of graft-versus-host disease (GVHD) and prognostic factors for patients with myelodysplastic syndrome (MDS) after allogeneic hematopoietic cell transplantation (allo-HCT), we retrospectively reviewed 115 patients with MDS or acute myeloid leukemia with multilineage dysplasia (AML-MLD) after allo-HCT at our center. Eighty one patients received reduced-intensity conditioning (RIC) regimens, whereas 34 received myeloablative conditioning regimens. Although the RIC group was significantly older and included more patients with poor cytogenetic risk, no difference in 4-yr overall survival (OS) was seen between the two groups. In a multivariate analysis, covariates associated with a worse OS were the French-American-British stage of refractory anemia excess blasts in transformation/AML-MLD at peak, poor cytogenetic risk, bone marrow blasts of 20% or higher at HCT and the absence of chronic GVHD (cGVHD). By using semi-landmark analyses, we found that the presence of cGVHD significantly improved OS in high-risk patients or the RIC group. However, there was no difference in OS between those with and without cGVHD among low-risk MDS patients. These findings suggest that the graft-versus-leukemia effect may be more beneficial in high-risk patients who do not receive intensive preparative regimens.

Comparison of outcomes after allogeneic hematopoietic stem cell transplantation in patients with follicular lymphoma, diffuse large B-cell lymphoma associated with follicular lymphoma, or de novo diffuse large B-cell lymphoma.

The outcome after allogeneic hematopoietic stem cell transplantation (allo-HCT) for diffuse large B-cell lymphoma (DLBCL) associated with follicular lymphoma (FL), which includes DLBCL with pre- or co-existing FL, remains controversial, and few previous reports have compared the outcomes after allo-HCT for FL, DLBCL associated with FL, and de novo DLBCL. We retrospectively analyzed 97 consecutive patients with FL (n = 46), DLBCL associated with FL (n = 22), or de novo DLBCL (n = 29) who received allo-HCT at our institute between 2000 and 2010. With a median follow-up of 53 months, the 5-year overall survival (OS) and progression-free survival (PFS) were, respectively, 77% and 70% for FL, 62% and 57% for DLBCL associated with FL, and 26% and 23% for de novo DLBCL. The 5-year cumulative incidences of non-relapse mortality and disease progression/relapse were, respectively, 16% and 15% for FL, 19% and 24% for DLBCL associated with FL, and 36% and 41% for de novo DLBCL. By a multivariate analysis, the OS and PFS for DLBCL associated with FL were significantly better than those for de novo DLBCL, whereas they were not significantly different from those for FL. These results suggest that allo-HCT may be a promising option for patients with not only advanced FL but also DLBCL associated with FL.

Characterization of readmission after allogeneic hematopoietic cell transplantation.

To elucidate the incidence, causes, and risk factors associated with readmission due to transplant-related complications, we studied 213 consecutive patients who were discharged without progression of primary disease after their first allogeneic hematopoietic cell transplantation at our center between 2013 and 2016. The median patient age was 50 years (range, 18-71 years). Eighty-three patients had AML or MDS, 66 had lymphoma, 28 had ALL, 23 had ATL, and 13 had other diseases. The median duration of hospitalization for transplantation was 56 days (range 27-325 days). The cumulative incidences of readmission due to transplant-related complications were 8% at 30 days, 16% at 100 days, and 25% at 1 year after discharge. The most frequent cause of readmission was infection, followed by graft-versus-host disease throughout the first year. In multivariate analysis, steroid use at discharge was the only risk factor associated with readmission within 30 days, and steroid use at discharge, absolute lymphocyte count < 500/µl at discharge, and documented bacterial infection during admission were risk factors associated with readmission within 1 year. Our results indicated that factors during hospitalization or discharge, but not at transplantation, were associated with readmission. Patients with these risk factors should be monitored carefully after discharge.

Clinicopathological analysis of primary refractory diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone chemoimmunotherapy.

BACKGROUND: Approximately 15% of patients with diffuse large B-cell lymphoma (DLBCL) experience refractory or early relapsed disease after initial rituximab-containing chemoimmunotherapy is regarded as a primary refractory disease. Although the standard treatment for relapsed DLBCL is high-dose chemotherapy and autologous stem cell transplantation (HDC-ASCT), the efficacy of this approach for primary refractory DLBCL is not well understood. We aimed to investigate the clinicopathological characteristics and outcomes of patients with primary refractory DLBCL. METHODS: Sixty-nine consecutive patients with primary refractory DLBCL who were treated at our institution were categorized as partial responders (partial response to rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone [R-CHOP] or relapse within 6 months of R-CHOP) (n = 41) or primary progressors (no response to R-CHOP) (n = 28). Survival curves were constructed using the Kaplan-Meier method and compared using the log-rank test. RESULTS: At initial diagnosis, 70% of patients had Ann Arbor stage III/IV disease, 56% had non-germinal center B-cell-like type DLBCL, and 42% had double-expressor lymphoma (MYC and BCL2 expression). The 3-year overall survival rate was significantly poorer in the primary progressors group than in the partial responders' group (15% vs. 48%, p < 0.001). Four of 17 patients treated with HDC-ASCT were primary progressors; only one patient survived without relapse. Although double-expressor lymphoma status did not significantly impact overall survival among all patients (p = 0.794), it was identified as an independent poor prognostic factor in HDC-ASCT-treated patients (p = 0.002). CONCLUSIONS: We identified a subgroup of patients with primary refractory DLBCL who may not benefit from current treatment strategies. Further treatment development is needed to improve the outcomes of these patients.

Impact of low-dose anti-thymocyte globulin on immune reconstitution after allogeneic hematopoietic cell transplantation.

How low-dose anti-thymocyte globulin (ATG) for prophylaxis of graft-versus-host disease (GVHD) influences immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HCT) remains incompletely understood. We prospectively enrolled 41 consecutive adult patients and conducted cytometry-based immunophenotyping for 12 months after allo-HCT. Rabbit ATG (Thymoglobulin) was administered at a median total dose of 1.75 mg/kg in 16 of the 41 patients. Compared with patients who did not receive ATG, those who did had a significantly smaller number of naïve T cells (especially CD4+ ) within three months after allo-HCT. No significant difference was observed between the two groups in the reconstitution of other T cells (effector, memory, Th1, Th2, Th17, Treg, and Tfh), B cells (transitional, naïve, memory, and plasmablast), NK cells (regulatory and cytolytic), or dendritic cells (myeloid and plasmacytoid). Patients with fewer CD4+ naïve T cells than the median count (7.60 cells/µL) at two months after allo-HCT developed chronic GVHD less frequently than those with CD4+ naïve T cells above the median count (2-year cumulative incidences were 0.31 and 0.53, respectively; p = 0.133). This pilot study suggests low-dose Thymoglobulin suppresses the recovery of naïve T cells after allo-HCT, which may contribute to a lower incidence of chronic GVHD.

Prognostic significance of low pre-transplant skeletal muscle mass on survival outcomes in patients undergoing hematopoietic stem cell transplantation.

Little is known about the prognostic significance of muscle loss for allogeneic hematopoietic stem cell transplantation (allo-HCT). We retrospectively analyzed consecutive patients who received allo-HCT from 2013 to 2015. All patients underwent computed tomography (CT) imaging and bioelectrical impedance analysis (BIA) within 30 days before allo-HCT. Skeletal muscle area (cm2) at the third lumbar vertebra level on CT imaging and skeletal muscle mass (kg) measured by BIA were normalized by height in meters squared (m2) to calculate the skeletal muscle area index (SMI) and skeletal muscle mass index (SMMI). SMI and SMMI were significantly correlated (r = 0.744; P < 0.001). The cumulative incidence of 1-year non-relapse mortality (NRM) was significantly higher in patients with low SMI than high SMI (17% versus 0%, respectively; P = 0.023). Overall survival was shorter in patients with low SMI than high SMI (56% versus 93%, respectively; P < 0.001). In univariate analysis, low SMI was associated with increased risk of NRM (HR 7.46; 95% CI 1.05-52.98; P = 0.044), and in multivariate analysis it was associated with higher overall mortality (HR 5.35; 95% CI 1.71-16.72; P = 0.004). These results suggest that low muscle mass is an independent predictor of mortality after allo-HCT.

High-dose therapy and autologous stem cell transplantation for relapsed or high-risk diffuse large B-cell lymphoma: a nationwide survey.

To investigate the use of high-dose therapy and autologous stem cell transplantation (ASCT) for relapsed or high-risk diffuse large B-cell lymphoma (DLBCL) between 1990 and 2007, we conducted a nationwide survey using the registry database of the Japan Society for Hematopoietic Cell Transplantation. Of the 1222 patients in the database, 576 (47%) received ASCT in first complete remission (CR1), 140 (12%) in first partial remission, 281 (23%) in sensitive relapse, 150 (12%) in resistant or sensitivity-unknown relapse, and 75 (6%) in primary refractory status. With a median follow-up of 22 months, the 2-year overall survival (OS) and progression-free survival rates were 71% and 68%, respectively. The cumulative incidences of 2-year non-relapse mortality and relapse/progression were 6% and 26%, respectively. Relapse/progression after ASCT in the rituximab era (2002-2007) was significantly lower than that in the pre-rituximab era (1990-2001; P < 0.001). Older age, male gender, poor performance status at ASCT, non-CR1 at ASCT, ASCT performed in 1990-2001, and LEED or MCEC regimen were adverse predictors of OS. Because ASCT for newly diagnosed high-risk DLBCL has not been performed recently, a registry database study to assess the impact of ASCT for relapsed or refractory DLBCL in the rituximab era is warranted.

Retraction Note to: High-dose therapy and autologous stem cell transplantation for relapsed or high-risk diffuse large B-cell lymphoma: a nationwide survey.

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1007/s12185-020-03018-1.

Transformation Scoring System (TSS): A new assessment index for clinical transformation of follicular lymphoma.

Although histologic analysis is the gold standard for diagnosing follicular lymphoma (FL) transformation, many patients are diagnosed with transformation by clinical factors as biopsy specimens often cannot be obtained. Despite the frequency of clinical diagnosis, no clinical assessment tool has yet been established for FL transformation in the rituximab era. We derived and validated a transformation scoring system (TSS) based on retrospective analyses of 126 patients with biopsy-proven FL and histologic transformation (HT) at two hospitals of the National Cancer Center of Japan. In the derivation set (76 patients), the detailed analyses of the clinical characteristics at disease progression showed that lactate dehydrogenase (LDH) elevation, focal lymph nodal (LN) enlargement, hemoglobin <12 g/dl, and poor performance status (PS) (2-4) were associated with HT. The weights of these variables were decided based on the regression coefficients. Next, we constructed a TSS encompassing the above four factors: LDH, (> upper limit of normal [ULN], ≤ULN ×2) (1 point), (≥ULN ×2) (2 points); focal LN enlargement, (≥3 cm, <7 cm) (1 point), (≥7 cm) (2 points); hemoglobin <12 g/dl (1 point); poor PS (2 points). We identified a high positive predictive value (PPV) (96.4%) and negative predictive value (NPV) (85.4%) for diagnosing HT when a cutoff score of 2 was selected for our TSS. In an external validation set (50 patients), the probability of HT was high with scores ≥2 (PPV, 93.3%; NPV, 82.9%). We developed a TSS that offers a simple, yet, valuable tool, for diagnosing HT, especially in patients who cannot undergo biopsy.

Outcome of 93 patients with relapse or progression following allogeneic hematopoietic cell transplantation.

Relapse/progression after allogeneic hematopoietic cell transplantation (allo-HCT) remains the major cause of treatment failure. In this study, the subsequent clinical outcome was overviewed in 292 patients with leukemia/myelodysplastic syndrome who received allo-HCT. Among them, 93 (32%) showed relapse/progression. Cohort 1 was chosen to receive no interventions with curative intent (n = 25). Cohort 2 received reinduction chemotherapy and/or donor lymphocyte infusion (n = 48), and Cohort 3 underwent a second allo-HCT (n = 20). Sixty-three patients received reinduction chemotherapy, and 27 (43%) achieved subsequent complete remission (CR). The incidence of nonrelapse mortality (NRM) was similar among the three cohorts (4, 15, and 5%). The 1-year overall survival (OS) after relapse was significantly better in patients with a second HCT (58%) than in others (14%, Cohorts 1 and 2; P <.001). However, the 2-year OS did not differ between the two groups, which suggests that it is difficult to maintain CR after the second HCT. Multivariate analysis showed that reinduction chemotherapy, CR after intervention, second HCT, and longer time to post-transplant relapse were associated with improved survival. In conclusion, for patients with relapse after allo-HCT, successful reinduction chemotherapy and a second HCT may be effective for prolonging survival without excessive NRM. However, effective measures to prevent disease progression after a second HCT clearly need to be developed.