Prognostic factors in patients in the terminal phase of haematological malignancies who are receiving home medical care.

Although there are many prognostic models for patients in the terminal phase of solid tumours, a reliable prognostic scoring system in patients in the terminal phase of haematological malignancies (HM) has not been established. We retrospectively evaluated 180 patients in the terminal phase of HM who were receiving home medical care (HMC). Multivariate analyses revealed that clinician's estimate, consciousness, loss of appetite, dyspnoea, neutrophil count, lymphocyte count, and lactate dehydrogenase were associated with overall survival (OS). Based on this result, we developed a novel prognostic scoring system, the Japan palliative haematological oncology prognostic estimates, in which four risk groups were shown to clearly differ in survival (p < 0.001): a low-risk group (n = 41, median OS of 434 days), an intermediate-low-risk group (n = 80, median OS of 112 days), an intermediate-high-risk group (n = 38, median OS of 31.5 days), and a high-risk group (n = 21, median OS of 10 days). This is the first investigation of prognostic factors that influence the OS of patients in the terminal phase of HM who are receiving HMC. Providing patients with reliable information about their prognosis is important for them to consider how to spend their remaining life.

Comparison of alemtuzumab, anti-thymocyte globulin, and post-transplant cyclophosphamide for graft-versus-host disease and graft-versus-leukemia in murine models.

Graft-versus-host disease is a major complication after allogeneic hematopoietic stem cell transplantation for hematological malignancies. Immunosuppressive drugs, such as anti-thymocyte globulin, alemtuzumab, and post-transplant cyclophosphamide, have been used to prevent graft-versus-host disease in HLA-mismatched haploidentical hematopoietic stem cell transplantation. Here, we investigated whether these drugs could ameliorate graft-versus-host disease without diminishing the graft-versus-leukemia effect by using a xenogeneic transplanted graft-versus-host disease/graft-versus-leukemia model. Anti-thymocyte globulin treatment diminished graft-versus-host disease symptoms, completely depleted the infiltration of inflammatory cells in the liver and intestine, and led to prolonged survival. By contrast, improvement after post-transplant cyclophosphamide treatment remained minimal. Alemtuzumab treatment modestly prolonged survival despite an apparent decrease of Tregs. In the graft-versus-leukemia model, 1.5 to 2.0 mg/kg of anti-thymocyte globulin and 0.6 to 0.9 mg/kg of alemtuzumab reduced graft-versus-host disease with minimal loss of graft-versus-leukemia effect. Mice treated with 400 mg/kg of post-transplant cyclophosphamide did not develop graft-versus-host disease or leukemia, but it was difficult to evaluate the graft-versus-leukemia effect due to the sensitivity of A20 cells to cyclophosphamide. Although the current settings provide narrow optimal therapeutic windows, further studies are warranted to maximize the benefits of each immunosuppressant.

Mesenchymal Stromal Cells Inhibit Aerobic Glycolysis in Activated T Cells by Negatively Regulating Hexokinase II Activity Through PD-1/PD-L1 Interaction.

Mesenchymal stromal cells (MSCs) have been shown to inhibit aerobic glycolysis in activated T cells, leading to increased autophagy. Although tryptophan depletion induced by indoleamine 2,3-dioxygenase (IDO) generated by MSCs has been suggested as a potential mechanism, we found that this inhibition was completely abolished when T cells were physically separated from MSCs using the Transwell system. Instead, in the current study, we demonstrate that programmed cell death 1 receptor (PD-1) and its ligand PD-L1, the expression of which is induced on activated T cells and MSCs, respectively, in response to IFN-γ are involved in this inhibition. Blockade of PD-1/PD-L1 interaction by blocking antibodies significantly restored glucose uptake, glycolytic activity, and cluster formation of activated T cells, whereas a specific inhibitor of IDO, 1-methyl-DL-tryptophan, had no effect. Neither surface nor cytoplasmic glucose transporter-1 expression on T cells was changed by MSCs. In addition, glycolytic gene expression in activated T cells was not inhibited despite the presence of MSCs. However, we found that hexokinase II (HK2) protein expression was markedly decreased in activated T cells that had been cocultured with MSCs. PD-1 blocking antibody restored HK2 expression. Taken together, our findings indicate that the PD-1/PD-L1 axis is involved in the MSC-mediated suppression of T cell glycolysis by negatively regulating HK2 activity at the protein level, but not at the mRNA level.

Steep neutrophil recovery following unrelated bone marrow transplantation is a major risk factor for the development of acute graft-vs-host disease-a retrospective study.

The speed of neutrophil recovery following allogeneic hematopoietic cell transplantation (allo-HCT) varies widely among patients. We retrospectively evaluated the slope of neutrophil recovery (N slope) in 120 patients who underwent a first unrelated bone marrow transplantation with granulocyte-colony-stimulating factor support between 2009 and 2018. The median N slope was 205.5/µl/day. We classified patients into low (n = 59) and high (n = 61) N slope groups with a cutoff value of 200/µl/day. The high N slope group correlated with older patients, RIC regimen, high CD34+ cells, and recent transplantation. The cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) was significantly higher in the high N slope group than in the low N slope group (44.3% vs. 16.9%, P < 0.001). In multivariate analysis, high N slope was identified as a significant independent risk factor for grade II-IV aGVHD, irrespective of the involved organs. There were no differences in relapse, nonrelapse mortality, or overall survival between the two groups. In conclusion, the difference in N slope after allo-HCT may predict the risk of aGVHD. Prevention and treatment of GVHD according to the changes in the neutrophil count may improve post-transplant complications.

Impact of prednisolone dosage in the CHOP regimen for follicular lymphoma: a retrospective study.

Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) is one of the standard regimens for indolent B-cell non-Hodgkin's lymphoma (NHL). It is unclear whether the prednisolone (PSL) dosage affects the therapeutic effect or the adverse event profile. We retrospectively examined 48 patients with indolent B-cell NHL who were treated with R-CHOP (PSL 50 mg/m2/day for 5 days) at our institute between 2006 and 2016. We compared them with 149 patients with indolent B-cell lymphoma who were treated with R-CHOP (PSL 100 mg for 5 days) in the JCOG 0203 trial. The proportions of patients with bulky disease, extranodal involvement, and increased nodal sites were higher at our institute. Nevertheless, there was no difference in the CR rate, PFS, OS or the frequency of adverse events, except for peripheral neuropathy, between the two treatment groups. In our institute, there was no difference in the CR rate, PFS, OS or adverse event profile between patients who received PSL at 60-80 mg/day and at 81-100 mg/day. Patients who received PSL at 60-80 mg/day included many female and light-weight patients. In conclusion, the PSL dose adjusted based on body surface area appeared to be appropriate in terms of efficacy and safety.

Factors that predict delayed platelet recovery after autologous stem cell transplantation for lymphoma or myeloma.

The amount of infused CD34+ cells has been reported to be the strongest predictor of platelet recovery after autologous stem cell transplantation (ASCT). However, the timing of platelet recovery varies widely among patients even after the infusion of similar amounts of CD34+ cells. Therefore, we retrospectively assessed 99 patients who underwent their first ASCT for lymphoma or myeloma at our center. Thirteen patients (13%) did not achieve platelet engraftment, defined as a platelet count of at least 2.0 × 104/µL without transfusion, at day 28 after transplantation, whereas 58 of 60 patients (97%) who received at least 2.0 × 106/kg CD34+ cells achieved platelet engraftment within 28 days. Multivariate analysis identified the following significant risk factors for delayed platelet recovery: hemoglobin level and platelet count before stem cell harvest, body temperature of > 39 °C within 5 days after ASCT, and infusion of a small amount (< 2.0 × 106/kg) of CD34+ cells. In a subgroup analysis of 39 patients infused with < 2.0 × 106/kg CD34+ cells, a need for repeated apheresis for stem cell harvest and a body temperature of > 39 °C within 5 days after ASCT were identified as independent factors for delayed platelet recovery. In summary, platelet recovery following ASCT was affected by insufficient hematopoietic recovery at stem cell harvest, a need for repeated apheresis, and high fever early after ASCT, particularly when the amount of infused stem cells was insufficient.

Comparison of Danaparoid Sodium and Synthetic Protease Inhibitors for the Treatment of Disseminated Intravascular Coagulation Associated with Hematological Malignancies: A Retrospective Analysis.

BACKGROUND: Danaparoid sodium and synthetic protease inhibitors (SPIs) have been approved for the treatment of disseminated intravascular coagulation (DIC) in Japan. OBJECTIVES: To compare the clinical results of the treatment of DIC with danaparoid or SPIs. METHODS: We retrospectively examined 188 patients with hematological malignancy-related DIC. RESULTS: DIC resolution rate in the danaparoid group was higher than that in the SPIs group (61.5 vs. 42.6%; p = 0.031) on day 7. Multivariate analysis identified the response to chemotherapy as independent predictive factor for DIC resolution on day 7 (odds ratio, OR, 2.28; 95% confidence interval, CI, 1.21-4.31; p = 0.011). While there was no significant difference in the DIC resolution rate on day 14 (75.0 vs. 62.4%; p = 0.117), in a subgroup analysis of patients who did not show an improvement in the underlying disease, the danaparoid group showed a significantly better DIC resolution rate (OR 3.89; 95% CI 1.15-13.2; p = 0.030). There was no difference in the rate of cumulative mortality from bleeding within 28 days between the 2 groups (6.6 vs. 3.3%; p = 0.278). CONCLUSIONS: Danaparoid may be associated with more frequent resolution of DIC in patients with refractory underlying disease.

Evaluation of thrombotic events in patients with immune thrombocytopenia.

Immune thrombocytopenia (ITP) has been reported to be associated with thrombotic events. The incidence of thrombosis in 303 newly diagnosed ITP patients in our institute between 2000 and 2016 was retrospectively reviewed. During a median follow-up of 3.6 years, 16 thrombotic events (12 arterial and four venous) occurred. The median platelet count at thrombotic events was 102 × 109/l. At 10 years, the cumulative thrombosis incidence was 10%. A univariate analysis showed that smoking, hypertension, male gender, a history of thrombosis, and atrial fibrillation (Af) were significantly associated with the occurrence of thrombosis, and a multivariate analysis identified smoking and Af as independent risk factors. The thrombotic risk was not increased by lupus anticoagulant positivity or ITP treatment. At 5 years, the cumulative incidence of bleeding and overall survival probability was 5.6% and 92%, respectively. This study demonstrates that smoking and Af were associated with an increased risk of thrombosis. Previously identified risk factors were not confirmed in these Japanese ITP patients.

Alloreactive T Cells Display a Distinct Chemokine Profile in Response to Conditioning in Xenogeneic GVHD Models.

BACKGROUND: Chemokines and chemokine receptors are potential targets for the prevention and treatment of graft-versus-host disease (GVHD). The objective of the current study is to determine the clinical relevance of xenogeneic transplantation models in terms of host and donor chemokine profiles and, if this is the case, to assess the clinical efficacy of C-C chemokine receptor (CCR) 5 antagonist maraviroc for the prevention of GVHD using this model. METHODS: Xenogeneic GVHD was induced by intravenous injection of 5 × 10 human pan T cells into NOD/Shi-scid-IL2rγ (NOG) mice or MHC class I/II-deficient NOG mice in the presence or absence of total body irradiation before transplantation. RESULTS: Extensive tissue destruction with human T-cell infiltration was observed throughout the body, particularly in lungs and liver, but relatively mild in gut. Consistent with this finding, quantitative polymerase chain reaction confirmed the upregulation of mouse CXC chemokine ligand (CXCL) 9 and CXCL10 in lungs and CCL4 in lungs and liver but not in gut. The addition of total body irradiation (1) led to the early release of mouse CCL4 and CXCL10, (2) upregulated a number of chemokine-related genes in human T cells, (3) induced higher expression of CCR5 on human CD4 and CD8 T cells and CXCR3 on human CD4 T cells, and (4) promoted their migration and proliferation in organs, resulting in more severe tissue damage. In this context, pharmacological CCR5 blockade neither ameliorated GVHD nor prolonged survival in NOG mice. CONCLUSIONS: Our experimental data do not demonstrate clinical benefit of CCR5 antagonist for the prevention of GVHD in a myeloablative setting.

Predictive value of soluble interlukin-2 receptor level at diagnosis on the outcome for patients with classical Hodgkin lymphoma treated with ABVD with or without radiotherapy.

We retrospectively analyzed 70 patients with classical Hodgkin lymphoma (cHL) who were treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) with or without radiotherapy to assess the influence of the soluble interleukin-2 receptor (sIL-2R) level at diagnosis on the clinical outcome. Receiver operating characteristic analyses determined that the optimal cutoff value of the sIL-2R level for progression-free survival (PFS) was 2490 U/mL. Using this cutoff value, patients were classified into low (n = 46) and high (n = 24) sIL-2R groups. The patients in the high sIL-2R group exhibited a significantly inferior PFS (44.1% vs. 90.4% at 5 years, P < 0.001) and overall survival (OS) (67.6% vs. 94.7% at 5 years, P = 0.001) compared with those in the low sIL-2R group. Multivariate analysis showed that a high sIL-2R level was an independent prognostic factor for PFS after adjusting for stage, white blood cell, hemoglobin, and B symptoms, and also OS after adjusting for age and stage (hazard ratio (HR) 6.49, P < 0.001 and HR 5.98, P = 0.009, respectively). In patients with advanced-stage cHL, a high sIL-2R level predicted 5-year PFS even after adjustment for international prognostic score > 4 (HR 6.00, P = 0.007). These results demonstrate that the sIL-2R level can be a useful prognostic factor in patients with cHL treated with ABVD with or without radiotherapy.

Impact of the soluble interleukin-2 receptor level in the relapsed or refractory phase on the clinical outcome of patients with diffuse large B-cell lymphoma.

This study sought to investigate the impact of the soluble interleukin-2 receptor level in the relapsed or refractory phase (r/r sIL-2R) on the clinical outcome in patients with diffuse large B-cell lymphoma (DLBCL). We determined the optimal cutoff value of r/r sIL-2R for disease progression within 6 months from salvage chemotherapy to be 861 U/mL. The high r/r sIL-2R group exhibited a significantly lower survival rate than the low r/r sIL-2R group (1-year event-free survival [EFS], 22.6% vs. 55.7%, p < .001 and 1-year overall survival [OS], 45.9% vs. 75.1%, p < .001). Independent significant correlations were observed between r/r sIL-2R and both inferior 1-year EFS and OS in a multivariate analysis (hazard ratio [HR]: 2.69, 95% CI: 1.61-4.51, p < .001 and HR: 2.99, 95% CI: 1.57-5.70, p < .001). This study demonstrates that r/r sIL-2R could be useful for predicting a poor prognosis in patients with r/r DLBCL.

TAFRO Syndrome with an Anterior Mediastinal Mass and Lethal Autoantibody-Mediated Thrombocytopenia: An Autopsy Case Report.

TAFRO syndrome, a rare systemic inflammatory disease, can lead to multiorgan failure without appropriate treatment. Although thrombocytopenia is frequently seen in patients with TAFRO syndrome, little is known about its pathogenesis. Moreover, while recent studies have reported the presence of an anterior mediastinal mass in some patients, the pathological status of this remains unclear. Here, we report a case of fatal bleeding in a patient with TAFRO syndrome accompanied by an anterior mediastinal mass. A 55-year-old female was transferred to our hospital with a 2-week history of fever, epistaxis, and dyspnea. Laboratory tests revealed severe thrombocytopenia, computed tomography (CT) showed pleural effusions, and bone marrow biopsy revealed reticulin myelofibrosis. We suspected TAFRO syndrome, but the CT scan showed an anterior mediastinal mass that required a biopsy to exclude malignancy. She soon developed severe hemorrhagic diathesis and died of intracranial hemorrhage despite intensive treatment. She had multiple autoantibodies against platelets, which caused platelet destruction. An autopsy of the mediastinal mass revealed fibrous thymus tissues with infiltration by plasma cells. Our case suggests that thrombocytopenia could be attributed to antibody-mediated destruction and could be lethal. Hence, immediate treatment is imperative in cases of severe thrombocytopenia, even when accompanied by an anterior mediastinal mass.

Comparison of neutropenia profiles in different treatment protocols for acute myeloid leukemia using the D-index.

Neutropenia is a major risk factor for opportunistic infections in patients with acute myeloid leukemia (AML) who undergo chemotherapy. In the present study, we retrospectively compared the D-index, which reflects both the depth and duration of neutropenia, between two different chemotherapy regimens for AML. Sixty-seven patients with AML were included: 37 received an induction regimen of daunorubicin (DNR) and cytarabine followed by consolidation therapies consisting of standard-dose cytarabine (SDAC) and other antineoplastic agents; the remaining 30 received idarubicin (IDR) and cytarabine as remission induction therapy followed by high-dose cytarabine (HDAC). The duration of neutropenia was shorter, but the D-index was higher, with IDR than with DNR. The total D-index during the entire consolidation therapies was significantly higher with SDAC than with HDAC. In conclusion, the neutropenia profile differs between treatment regimens, and thus, physicians should plan the management of infectious complications according to the neutropenia profile for each regimen.

Comparison of blast percentage calculated based on bone marrow all nucleated cells and non-erythroid cells in myelodysplastic syndromes with erythroid hyperplasia.

It is controversial whether blast percentage based on all nucleated cells (ANC) or non-erythroid cells (NEC) more accurately reflects the prognosis of patients with myelodysplastic syndromes (MDS). We considered that the impact of blast percentage on survival should be similar in MDS with erythroid hyperplasia (MDS-E) and MDS with no erythroid hyperplasia (MDS-NE), and from this perspective, we retrospectively analyzed 322 patients, including 44 with MDS-E and 278 with MDS-NE. Overall survival was similar between the MDS-E and MDS-NE groups (P = 0.94). In a subgroup of patients with bone marrow (BM) blasts of < 5%, no difference in survival was found between MDS-E and MDS-NE by either calculation method. However, in patients with a blast percentage between 5 and 10%, a significant difference in survival was observed only when the blast percentage in MDS-E was calculated from ANC (P < 0.001 by ANC and P = 0.66 by NEC). A similar result was observed when we analyzed the remaining patients with higher blasts together with those with blasts between 5 and 10%. These results suggest that the calculation of the BM blast percentage based on NEC in MDS-E provides a blast percentage value with a clinical impact consistent with that in MDS-NE.

Associations between the peripheral blood Wilms tumor gene 1 level and both bone marrow blast cells and the prognosis in patients with myelodysplastic syndrome.

Wilms tumor gene 1 (WT1) is highly expressed in myelodysplastic syndrome (MDS) cells and is known to reflect the tumor burden in MDS. We evaluated the usefulness of WT1 mRNA levels for predicting the prognosis of MDS. At diagnosis, WT1 levels were strongly correlated with the percentage of blasts calculated based on non-erythroid cells, but not with that based on all nucleated cells (r = 0.57, p < .05 vs r = 0.42, p = .13). Among the allogeneic transplant recipients, the presence of two consecutive WT1 levels ≥100 copies/µg RNA with a median interval of one month was associated with a 77.8% relapse rate at nine months from the first detection of a high WT1 level, and the median time to relapse was only 114 [36-257] days. WT1 levels at diagnosis were correlated with known prognostic factors. In addition, the presence of two consecutive high WT1 levels after allogeneic transplantation may predict early relapse of MDS.

Comparison of gabexate mesilate and nafamostat mesilate for disseminated intravascular coagulation associated with hematological malignancies.

We evaluated clinical outcomes of disseminated intravascular coagulation (DIC) in patients with hematological malignancies treated with synthetic protease inhibitors (SPIs) and compared the effects of gabexate mesilate (FOY) and nafamostat mesilate (FUT). We retrospectively examined 127 patients [acute myeloid leukemia (n = 48), acute lymphoblastic leukemia (n = 25), and non-Hodgkin lymphoma (n = 54)] with DIC, who were diagnosed according to Japanese Ministry of Health, Labour and Welfare criteria and treated with SPIs [FOY (n = 55) and FUT (n = 72)] at our hospital from 2006 to 2015. The DIC resolution rates on days 7 and 14 were 42.6% and 62.4%, respectively. No significant differences were observed in DIC resolution rates between the FUT and FOY groups [40.3% vs. 45.5% (day 7), P = 0.586; 56.3% vs. 69.8% (day 14), P = 0.179, respectively]. Multivariate analysis revealed that response to chemotherapy was the only independent predictor of DIC resolution on days 7 and 14 (ORR 2.81, 95% CI 1.32-5.98, P = 0.007; ORR 2.51, 95% CI 1.12-5.65, P = 0.026). Resolution of DIC was correlated with improvement of background hematological malignancies, and no significant differences were observed between the two SPIs.

Role of Sequential Monitoring of WT1 Gene Expression in Patients With Acute Myeloid Leukemia for the Early Detection of Leukemia Relapse.

BACKGROUND: Wilms' tumor 1 (WT1) mRNA expression is a universal marker of minimal residual disease in patients with acute myeloid leukemia (AML). The aim of this retrospective study was to evaluate the ability of serial measurement of peripheral blood WT1 mRNA levels to predict relapse in patients with AML in remission. PATIENTS AND METHODS: From April 2012 to May 2015, 131 patients with AML were admitted to our hospital. Among them, 55 were examined for WT1 mRNA at least 3 times during complete remission to assess minimal residual disease, and thus were included in the following analyses. RESULTS: With a median follow-up duration of 921 days, 34 remained in remission, but their WT1 values frequently increased to 100 copies/µg RNA. Therefore, we focused on the 40 posttreatment observation periods of 37 patients who experienced high WT1 values (defined as those above 100 copies/µg RNA) at least once after they achieved remission. The cumulative incidence of hematologic relapse was 75.8% at 6 months in 26 patients with 2 consecutive high WT1 values, whereas just 1 of the 14 patients with only 1 high WT1 value relapsed (P < .01). Similar results were obtained in subgroup analyses of allogeneic stem cell transplant recipients. CONCLUSION: Sequential monitoring of the WT1 mRNA is of value for the early detection of hematologic relapse in patients with AML in remission after chemotherapy or stem cell transplantation.

False-positive elevation of 1,3-beta-D-glucan caused by continuous administration of penicillin G.

The 1,3-beta-D-Glucan (BDG) assay is widely used for the diagnosis of fungal infections, especially in patients with hematologic malignancies. Some antimicrobials have been reported to cause false-positive results for BDG, but there has been no report on the effect of penicillin G (PCG) on BDG levels. We experienced a patient who developed false-positive BDG elevation during the administration of PCG for osteomyelitis due to Streptococcus pneumoniae infection. The serum BDG level increased up to 81.0 pg/ml during the continuous administration of PCG at 24 million units per day. However, chest and paranasal CT scan showed no evidence of fungal infection. The BDG level decreased to 38.0 pg/ml at 14 hours after the discontinuation of PCG. The amount of BDG in one vial of PCG inferred from these serum BDG levels is very similar to the actual BDG concentration in a vial of PCG. Therefore, during the administration of PCG, elevated BDG levels should be interpreted with caution, as they may be false-positive results.

Comprehensive Analysis of the Activation and Proliferation Kinetics and Effector Functions of Human Lymphocytes, and Antigen Presentation Capacity of Antigen-Presenting Cells in Xenogeneic Graft-Versus-Host Disease.

Xenogeneic graft-versus-host disease (GVHD) models in highly immunodeficient mice are currently being used worldwide to investigate human immune responses against foreign antigens in vivo. However, the individual roles of CD4+ and CD8+ T cells, and donor/host hematopoietic and nonhematopoietic antigen-presenting cells (APCs) in the induction and development of GVHD have not been fully investigated. In the present study, we comprehensively investigated the immune responses of human T cells and the antigen presentation capacity of donor/host hematopoietic and nonhematopoietic APCs in xenogeneic GVHD models using nonobese diabetic/Shi-scid-IL2rgnull mice. CD4+ T cells and, to a lesser extent, CD8+ T cells individually mediated potentially lethal GVHD. In addition to inflammatory cytokine production, CD4+ T cells also supported the activation and proliferation of CD8+ T cells. Using bone marrow chimeras, we demonstrated that host hematopoietic, but not nonhematopoietic, APCs play a critical role in the development of CD4+ T cell-mediated GVHD. During early GVHD, we detected 2 distinct populations in memory CD4+ T cells. One population was highly activated and proliferated in major histocompatibility complex antigen (MHC)+/+ mice but not in MHC-/- mice, indicating alloreactive T cells. The other population showed a less activated and slowly proliferative status regardless of host MHC expression, and was associated with higher susceptibility to apoptosis, indicating nonalloreactive T cells in homeostasis-driven proliferation. These observations are clinically relevant to donor T cell response after allogeneic hematopoietic stem cell transplantation. Our findings provide a better understanding of the immunobiology of humanized mice and support the development of novel options for the prevention and treatment for GVHD.

Clinical outcomes of myeloid/lymphoid neoplasms with fibroblast growth factor receptor-1 (FGFR1) rearrangement.

OBJECTIVE: Myeloid/lymphoid neoplasms with fibroblast growth factor receptor-1 (FGFR1) rearrangement are hematopoietic stem cell disorders with a poor prognosis, but no established standard therapy. METHODS: We experienced a patient with T-lymphoblastic lymphoma (LBL) associated with FGFR1 rearrangement who underwent cord blood transplantation, but died of pulmonary complication. We collected the clinical data of patients with FGFR1 rearrangement from the medical literature and analyzed 45 patients, including our patient. RESULTS: The primary diagnoses were myeloproliferative neoplasm (MPN) or myelodysplastic syndromes (MDS) in 14 and acute leukemia or LBL in 31. In MPN and MDS patients, the cumulative incidence of transformation to blast phase (BP) at 12 months was 46.2%. The 1-year overall survival (OS) from diagnosis in all cases was 43.1%. With regard to the impact of treatment response on survival, the achievement of complete response with a landmark at 2 months after diagnosis of BP was associated with a superior OS (40.0% vs. 26.0% P = 0.011 for 1-year OS from BP). Allogeneic hematopoietic stem cell transplantation (HSCT) was performed in 13 patients, and the 1-year OS from allogeneic HSCT was 61.5%. The hazard ratio for mortality was 0.34 (95% CI, 0.08-1.51, P = 0.15) for allogeneic HSCT treated as a time-dependent covariate, which suggests that allogeneic HSCT may confer a clinical benefit. CONCLUSION: The further accumulation of clinical data is needed to determine the optimal therapeutic approach for these neoplasms.