Sulforaphene suppresses oesophageal cancer growth through mitogen- and stress-activated kinase 2 in a PDX mouse model.

BACKGROUND: Although sulforaphene has potential anticancer effects, little is known about its effect on oesophageal squamous cell carcinoma (ESCC) invasiveness. METHODS: To investigate whether sulforaphene inhibits the growth of oesophageal cancer cells, MTT and anchorage-independent cell growth assays were performed. Global changes in the proteome and phosphoproteome of oesophageal cancer cells after sulforaphene treatment were analysed by mass spectrometry (MS), and the underlying molecular mechanism was further verified by in vivo and in vitro experiments. RESULTS: Sulforaphene treatment markedly affected proteins that regulate several cellular processes in oesophageal cancer cells, and mitogen- and stress-activated kinase 2 (MSK2) was the main genetic target of sulforaphene in reducing the growth of oesophageal cancer cells. Sulforaphene significantly suppressed ESCC cell proliferation in vitro and reduced the tumour size in an oesophageal patient-derived xenograft (PDX) SCID mouse model. Furthermore, the binding of sulforaphane to MSK2 in vitro was verified using a cellular thermal dhift assay, and the effect of MSK2 knockdown on the ESCC phenotype was observed using a shMSK2 model. CONCLUSION: The results showed that sulforaphene suppresses ESCC growth in both human oesophageal squamous cells and PDX mouse model by inhibiting MSK2 expression, implicating sulforaphene as a promising candidate for ESCC treatment.

Single VHH-directed BCMA CAR-NK cells for multiple myeloma.

Natural killer (NK) cells are promising alternatives for the production of "off-the-shelf" CAR products, posing a lower risk of cytokine release syndrome (CRS) than CAR-T cells. We synthesized four single VHH-directed anti-BCMA CARs, incorporating various intracellular regions (2B4 versus CD28) and hinge domains (CD28 versus IgG1) and ectopically producing IL-15. NK cells derived from peripheral blood (PB) were expanded ex vivo by K562-mbIL21 feeder cells. Stable CAR transduction was obtained through lentiviral transduction with the BaEV-Rless pseudotyped lentiviral vector. BCMA-CD28-IL15 CAR-NK cells with ectopic expression of IL-15 exhibited superior cytotoxicity were compared to BCMA-CD28 CAR-NK cells lacking IL-15 and BCMA-hIgG1-IL15 CAR-NK cells with an IgG1 hinge domain. We further assessed the cytotoxic capabilities of BCMA-2B4-IL15 CAR-NK cells with 2B4 intracellular domain. The BCMA-CD28-IL15 CAR-NK cells revealed stronger cytotoxicity and higher cytokine secretion against BCMA+ tumor cells than BCMA-2B4-IL15 CAR-NK cells in vitro. In the MM.1S-Luc mouse model, BCMA-CD28-IL15 CAR-NK inhibited the growth of tumor cells and prolonged mouse survival. These results show that the single VHH-directed BCMA CAR-NK cells exhibited remarkable specific killing ability, making them a potential candidate for immunotherapy in multiple myeloma treatment.

A retrospective study of autologous hematopoietic stem cell transplantation for peripheral T-cell lymphoma: pre-transplant patients with partial remission benefit from post-transplant maintenance therapy.

Background: Whether autologous hematopoietic stem cell transplantation (ASCT) improves the survival of patients with peripheral T-cell lymphoma (PTCL) remains controversial. Some studies have demonstrated that the efficacy of ASCT is superior in patients with complete remission (CR), whereas patients with partial remission (PR) remain vulnerable to relapse after ASCT, resulting in decreased survival rates. Maintenance therapy after chemotherapy may reduce the relapse rate of PTCL and improve survival; however, the role of maintenance therapy after ASCT in PTCL remains unclear. In this study, we aimed to analyze the efficacy of ASCT and post-transplant maintenance therapy in PTCL. Methods: We retrospectively analyzed the clinical data of 69 patients with PTCL who underwent ASCT at our center between November 2001 and November 2021. According to the patients' intention, thirty patients received post-transplant maintenance treatment, whereas 39 did not. The overall survival (OS) and progression-free survival (PFS) between the groups were compared using the log-rank test. Results: At a median follow-up of 36 months, the entire cohort's 3-year OS and PFS were 67.8% and 53.0%, respectively. The 3-year OS and PFS of patients with CR1, CR2, and PR were 85.3% and 65.4%, 80.0% and 60.0%, and 38.4% and 32.0%, respectively (OS: P=0.001; PFS: P=0.003). The relapse rates between the groups with or without maintenance therapy were 26.7% vs. 52.2%, the 3-year OS was 86.0% vs. 54.2% (P=0.004), and the 3-year PFS was 73.3% vs. 37.5% (P=0.004). Further analysis revealed that the efficacy of maintenance therapy was not significant in patients with CR1 and CR2, whereas patients with PR benefited from maintenance therapy. The relapse rate of patients with PR who received or did not receive maintenance therapy was 33.3% vs. 78.7%, 3-year OS was 66.7% vs. 21.9% (P=0.007), and 3-year PFS was 66.7% vs. 12.5% (P=0.004). Conclusions: Patients with CR in PTCL benefit from ASCT, and post-transplant maintenance therapy reduces the relapse rate and significantly improves OS and PFS in patients with PR.

Reduced-dose post-transplant cyclophosphamide plus low-dose post-transplant anti-thymocyte globulin as graft-versus-host disease prophylaxis with fludarabine-busulfan-cytarabine conditioning in haploidentical peripheral blood stem cell transplantation: A multicentre, randomized controlled clinical trial.

Anti-thymocyte globulin (ATG) or post-transplant cyclophosphamide (PTCy)-based regimens are widely used for graft-versus-host disease (GVHD) prophylaxis in haploidentical haematopoietic stem cell transplantation (haplo-HSCT). To improve the effectiveness of GVHD prophylaxis in haploidentical peripheral blood stem cell transplantation (haplo-PBSCT), we conducted a multicentre, randomized clinical trial to determine the efficacy of reduced-dose PTCy (40 mg/kg/d on days 3 and 4) combined with low-dose post-transplant ATG (2.5 mg/kg on day 8)-based GVHD prophylaxis (reduced-dose PTCy/ATG) with fludarabine-busulfan-cytarabine (FBA) conditioning for patients with haematological malignancies. From 2018 to 2022, 122 patients from four institutions were randomly assigned 1:1 to either a reduced-dose PTCy/ATG or a standard-dose ATG group ('Beijing Protocol', ATG: 10 mg/kg). All patients achieved myeloid engraftment. Cumulative incidences of grade II-IV (11.5% vs 39.3%, p = 0.001) and grade III-IV (6.6% vs 24.6%, p = 0.014) acute GVHD at day 100 were significantly reduced in the reduced-dose PTCy/ATG group. Furthermore, two-year overall survival, disease-free survival and GVHD-free/relapse-free survival were significantly improved in the reduced-dose PTCy/ATG group (75.4% vs 54.1%, p = 0.021; 72.7% vs 55.0%, p = 0.044; 61.3% vs 42.3%, p = 0.022 respectively). Our results demonstrate that the addition of low-dose ATG to reduced-dose PTCy with FBA conditioning is a promising strategy in haplo-PBSCT.

Case Report: Successful engraftment of allogeneic hematopoietic stem cells using CAR-T cell therapy as the conditioning regimen in R/R Ph+ B cell acute lymphoblastic leukemia.

Background: Consolidative allogeneic hematopoietic stem cells (allo-HSCs) after chimeric antigen receptor T cells (CAR-T) therapy is an emerging modality in hematologic malignancies. Knowledge about the success of allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CAR-T therapy without a conditioning regimen is limited. Case presentation: We report a patient with relapsed/refractory (R/R) Ph+ B-cell acute lymphoblastic leukemia (ALL) who underwent anti-CD19 CAR-T immunotherapy. After 1 month of treatment, bone marrow hyperplasia remained reduced with no hematopoietic improvements. In line with this, allogeneic hematopoietic stem cells (HSCs) were extracted from an HLA-matched sibling donor and administered to the patient on day 33 after CAR-T cell therapy to support hematopoiesis. On day 40, the level of immature bone marrow lymphocytes was at 0% and minimal residual disease-negative, and the fusion gene BCR/ABL 190 was negative. Chimerism analysis showed full donor chimerism. Three months after CAR-T cells infusion, the patient was still in complete remission with full donor chimerism. However, decreased liver function with skin pigmentation and festering, indicative of acute graft versus host disease, was noted. The treatment was halted owing to financial reasons. Conclusion: We report the successful engraftment of allogeneic HSCs using CAR-T cell therapy as a conditioning regimen for R/R B-ALL patients.

Low-dose post-transplant cyclophosphamide with low-dose antithymocyte globulin for prevention of graft-versus-host disease in first complete remission undergoing 10/10 HLA-matched unrelated donor peripheral blood stem cell transplants: a multicentre, randomized controlled trial.

The most widely used regimens of graft-versus-host disease (GVHD) prophylaxis in HLA-matched unrelated donor peripheral blood stem cell transplantation (MUD-PBSCT) are based on anti-thymocyte globulin (ATG) or post-transplant cyclophosphamide (PTCy). To improve the efficiency of GVHD prophylaxis, a novel regimen, composed of low-dose PTCy (20 mg/kg on day +3 and +4) and low-dose ATG (6 mg/kg), was evaluted in patients with hematological malignancies ungoing 10/10 HLA MUD-PBSCT in first remission (CR1). In our prospective, multicenter study, 104 patients were randomly assigned one-to-one to low-dose PTCy-ATG (n = 53) or standard-dose ATG (10 mg/kg, n = 51). Both the cumulative incidences (CIs) of grade II-IV acute GVHD (aGVHD) and chronic GVHD (cGVHD) at 2 years in low-dose PTCy-ATG cohort were significantly reduced (24.5% vs. 47.1%; P = 0.017; 14.1% vs. 33.3%; P = 0.013). The CI of non-relapse-mortality (NRM) was much lower (13.2% vs. 34.5%; P = 0.049) and GVHD-free, relapse-free survival (GRFS) was significantly improved at 2 years in low-dose PTCy-ATG arm (67.3% vs 42.3%; P = 0.032). The low-dose PTCy-ATG based GVHD prophylaxis is a promising strategy for patients in CR1 after 10/10 HLA MUD-PBSCT.

Successful outcomes of second hematopoietic stem cell transplantation for graft failure in pediatric patients with severe aplastic anemia.

Severe aplastic anemia (SAA) is a life-threatening hematological disorder. The major therapies include matched sibling donor (MSD)- hematopoietic stem cell transplantation (HSCT), matched unrelated donor (MUD)-HSCT and immunosuppressive therapy (IST). However, there are many problems that can occur after HSCT, and graft failure (GF) is one of the most serious complications. To find an effective treatment, we analyzed 10 cases of second HSCT to treat SAA pediatric patients who suffered from GF and concluded that second haploidentical family donors HSCT is an effective treatment. Moreover, adding a small dose of busulfan or 2 ~ 3 Gy total body irradiation (TBI) in nonmyeloablative regimens (NMAs) can promote the engraftment. Although the study also showed that PBSCs, as a source of stem cells, can promote the implantation of neutrophil cells, due to small sample size, more research is still needed.

Chronic disease management practices and factors associated with health-related quality-of-life for persons with chronic myeloid leukemia receiving tyrosine kinase inhibitor therapy.

BACKGROUND: The main objective of this study was to explore health-related quality of life (HRQoL) profiles, chronic disease management practices and key factors associated with HRQoL in 540 patients with chronic myeloid leukemia in chronic phase (CML-CP) administered tyrosine kinase inhibitors (TKIs). METHODS: Adult CML-CP patients treated with TKIs in Henan Cancer Hospital from March 2015 to October 2019 were assessed via questionnaires, including demographic characteristics, TKI medications, participation in CML disease management, and HRQoL, in a cross-sectional investigation. Respondents were anonymous. Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) was used to measure HRQoL. A multivariate linear regression model with stepwise entry was used to investigate variables independently associated with HRQoL domain and total scores. RESULTS: Totally, 540 respondents were included; 302 (55.93%) were male. Mean participant age was 42.90±13.00 years; 169 (31.3%), 178 (32.9%) and 193 (35.7%) individuals had a low, moderate or high disease management level, respectively. Except for insignificant event-free survival information, participants with higher disease management levels also had significantly higher rates of completing re-examination, drug withdrawal, cytogenetic response (CcyR) and/or major molecular response (MMR) (all P<0.01). Moreover, higher disease management level was accompanied by eight significantly higher HRQoL domains (all P<0.01). In multivariate linear regression analysis, variables significantly associated with a higher HRQoL included: (I) high disease management level (B=3.68, P=0.046); (II) transportation convenience (B=6.67, P<0.001); (III) family annual income >10,000 CNY (B=5.97, P<0.001); (IV) completed re-examination (B=4.58, P=0.036); (V) MMR (B=3.75, P=0.021) and CcyR (B=5.15, P=0.035). Female sex (B=-3.53, P=0.010), single status or divorce (B=-1.89 and -2.94, P=0.005 and 0.011), and low education level (B=-1.44, P=0.019) were significantly associated with lower HRQoL. CONCLUSIONS: Higher disease management level was significantly associated with higher elevated treatment efficacy and HRQoL in Chinese individuals with CML-CP administered TKIs. These data indicate the importance of chronic disease management on people's HRQoL and clinical outcome.

Metagenomic Next Generation Sequencing in the Detection of Pathogens in Cerebrospinal Fluid of Patients After Alternative Donor Transplantation: A Feasibility Analysis.

Central nervous system (CNS) complications can occur in 9%-15% of patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The clinical manifestations of the CNS complications are non-specific, with most of them being disturbances of consciousness, convulsions, headaches, fever, and epilepsy, making it difficult to infer the cause of the complications based on clinical manifestations. We retrospectively analyzed the sensitivity and feasibility of metagenomic next generation sequencing (mNGS) in the diagnosis of CNS infections after allo-HSCT. Lumbar punctures were performed on 20 patients with CNS symptoms after receiving alternative donor HSCT(AD-HSCT) at the Affiliated Cancer Hospital of Zhengzhou University from February 2019 to December 2020, and their cerebrospinal fluid (CSF) was collected. The mNGS technique was used to detect pathogens in the CSF. Routine CSF testing, biochemical analyses, G experiments, GM experiments, ink staining, acid-fast staining, and bacterial cultures were carried out, and quantitative PCR (qPCR) tests were used to detect cytomegalovirus (CMV), Epstein-Barr virus (EBV), BK polyomavirus (BKPyV), and human alphaherpesvirus (HHV). A total of 29 tests were performed with 21 of them being positive. Of the five negative patients, three were diagnosed with a posterior reversible encephalopathy syndrome, one as having transplantation-associated thrombotic microangiopathy, and one with transient seizure caused by hypertension. Fifteen patients tested positive, of which four had single infections and eleven had mixed infections. Five cases of fungal infections, six cases of bacterial infections, and 13 cases of viral infections were detected. Among the 13 cases of viral infections, ten cases were CMV(HHV-5); three were BKPyV; two were Torque teno virus (TTV); Two were HHV-1,two were EBV(HHV4), and one each of HpyV5 and HHV-6B. Thirteen patients tested positive for virus while the qPCR detection method of 6 identical specimens were below the minimum detection limit(<1×103 U/ml). The mNGS technique is highly sensitive, and it can be used to diagnose CNS infections after allo-HSCT.

Ruxolitinib early administration reduces acute GVHD after alternative donor hematopoietic stem cell transplantation in acute leukemia.

This study aimed to observe the safety and clinical efficacy of early application of ruxolitinib to prevent acute graft-versus-host disease (aGVHD) after alternative donor transplantation in acute leukemia. There were 57 patients undergoing allo-HSCT at the Affiliated Cancer Hospital of Zhengzhou University from July 2017 to October 2019. They were divided into control(16 patients) and ruxolitinib (41 patients) groups. For aGVHD prophylaxis, the control group received post-transplantation cyclophosphamide, antithymocyte globulin-Fresenius, cyclosporine A, and mycophenolate mofetil, while in the ruxolitinib group, ruxolitinib 5 mg/d in adults or 0.07-0.1 mg/(kg d) in children was administered from the day of neutrophil engraftment to 100 days post-transplantation based on control group. We found 55 patients had successful reconstitution of hematopoiesis; No significant difference was found in cGVHD, hemorrhagic cystitis, pulmonary infection, intestinal infection, Epstein-Barr virus infection, cytomegalovirus infection, relapse, death, and nonrelapse mortality. The incidences of aGVHD (50 vs. 22%, P = 0.046) and grade II-IV aGVHD (42.9 vs. 12.2%, P = 0.013) were significantly higher in the control group than in the ruxolitinib group. No significant differences were observed in overall survival (P = 0.514), disease-free survival (P = 0.691), and cumulative platelet transfusion within 100 days post-transplantation between two groups. This suggests early application of ruxolitinib can reduce the incidence and severity of aGVHD and patients are well tolerated.

Feasibility of reduced-dose posttransplant cyclophosphamide and cotransplantation of peripheral blood stem cells and umbilical cord-derived mesenchymal stem cells for SAA.

Posttransplant cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis is an effective strategie for patients receiving matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) and haploidentical HSCT (haplo-HSCT). We evaluated the effectiveness and safety of reduced-dose cyclophosphamide, 20 mg/kg for 13 patients in MSD-HSCT cohort and 25 mg/kg for 22 patients in haplo-HSCT cohort, on days + 3, + 4 combined with cotransplantation of peripheral blood stem cells (PBSCs) and human umbilical cord-derived mesenchymal stem cells (UC-MSCs) for severe aplastic anemia (SAA). In MSD-PTCy cohort, the times to neutrophil and platelet engraftment were significantly shorter than those in the MSD-control cohort (P < 0.05). The cumulative incidence of acute GVHD (aGVHD) at day + 100 (15.4%) was lower than that in the MSD-control cohort (P = 0.050). No patient developed chronic GVHD (cGVHD). The 1-year overall survival (OS) and event-free survival (EFS) rates were 100% and 92.3%. In haplo-PTCy cohort, the times to neutrophil and platelet engraftment were significantly shorter than those in the haplo-control cohort (P < 0.05). The cumulative incidences of aGVHD at day + 100 and 1-year cGVHD were 31.8% and 18.2%, and the 1-year OS and EFS rates were 81.8% and 66.9%. Reduced-dose PTCy and cotransplantation of PBSCs and UC-MSCs is an acceptable alternative to patients with SAA.

Second Allogeneic Hematopoietic Stem Cell Transplantation After Donor Replacement in Children With Severe Aplastic Anemia.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective measure for the treatment of severe aplastic anemia (SAA). While infection, graft failure, and graft-vs-host disease (GVHD) are the main causes of allo-HSCT failure, a second HSCT is needed to eliminate the dependence of blood transfusion and maintain disease-free survival. We applied low-dose total body irradiation (TBI) + fludarabine (FLU) + cyclophosphamide (CTX) + antilymphocyte globulin (ALG) + busulfan (BU) as a conditioning regimen of second HSCT after a transplantation with an HLA-mismatched donor. As for retransplantation donors, 1 child had an unrelated HLA-matched donor, and 2 children had related HLA-mismatched ones. The latter underwent more serious GVHD with a relatively high cytokine level, and the former had no obvious GVHD after the second HSCT. All 3 patients achieved a desirable effect within 1 month and received satisfactory therapeutic effect during the subsequent follow-up, indicating the convincing effectiveness and safety of this method.

Treatment of Epstein-Barr virus associated central nervous system diseases after allogeneic hematopoietic stem cell transplantation with intrathecal donor lymphocyte infusion.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective measure for the treatment of hematological disease. With the progress and widespread use of allo-HSCT, Epstein-Barr virus (EBV) related central nervous system (CNS) diseases have gotten more and more attention because of its poor prognosis and overall survival. Since currently there is no standard treatment for patients with EBV-associated CNS diseases and reported therapies are heterogeneous with mixed results, we attempted to develop a novel therapeutic method. We applied a regimen of intrathecal donor lymphocyte infusion (IDLI) in three patients with EBV-associated CNS diseases after allo-HSCT in addition to immunosuppressants reduction and combined antiviral therapy. All of three patients were responsive to this therapy: all clinical symptoms and EBV load in CSF were resolved 10, 17, and 12 days after initial IDLI, respectively, and magnetic resonance imaging (MRI) showed that lesions of case 1 and 2 disappeared 15 and 19 days after initial IDLI, respectively. Even more appealing, there were no acute or chronic adverse reactions during the infusion and up to 23 months of follow-up. In conclusion, IDLI seems to be an effective and safe method for EBV-associated CNS diseases in allo-HSCT recipients. We recommend this treatment modality for further investigation.

[Efficacy and Influencing Factors of Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma: Retrospective Analysis].

OBJECTIVE: To analyze the clinical efficacy and possible influencing factors of autologous hematopoietic Stem cell transplantation (auto-HSCT) in the treatment of patients with multiple myeloma (MM). METHODS: Clinical data of 40 MM patients received auto-HSCT in the Department of Hematology of Henan Cancer Hospital from September 2010 to November 2017 were retrospectively analyzed, the clinical curative efficiency was summarized and the related factors were analyzed. RESULTS: The curative efficiency of the patients before transplantation was 9(22.5%) with complete remission(CR), 5(12.5%) with very good partial remission(VGPR), 26(65%) with partial remission(PR), respectively, one of them was PR after 3 recurrences. The curative efficiency after transplantation was 22(55%) with complete remission(CR), 12(30%) with very good partial remission(VGPR), 6(15%) with partial remission(PR), respectively. And 2 cases were CR after double transplantation. Median follow-up time was 28.4 (3.1 to 88) months,15 cases presented disease progression, 7 cases were dead, 3-year estimated progression-free survival(PFS) and overall survival(OS) rate were 45.1% and 82% respectively. Unvariate analysis showed that the OS was affected by ISS stage (P<0.05), CR and VGPR (P<0.05) after transplantation; PFS was affected by ISS stage (P<0.01), before transplantation induction therapy (27 cases with bortezomizomi or thalidomide) (P<0.05), disease risk stratification (6 cases in high risk group) (P<0.05) , CR and VGPR (P<0.05) before transplantation, CR and VGPR (P<0.01) after transplantation. Cox multivariate regression analysis showed that the independent prognostic factors for OS were ISS stage, CR and VGPR after transplantation; the independent prognostic factors for PFS were the CR, VGPR, ISS stage after transplantation and induction therapy before transplant. CONCLUSION: Auto-HSCT can improve the clinical efficacy and survival rate of MM patients; ISS stage, CR and VGPR after transplantation are independent prognostic factors for OS and PFS, and induction therapy before transplantation is also an independent prognostic factor for PFS.

[Characteristics and clinical outcome of T315I mutation in Philadelphia chromosome-positive acute lymphoblastic leukemia and chronic myeloid leukemia].

OBJECTIVE: To investigate the characteristics and clinical outcome of T315I mutation in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) and chronic myeloid leukemia (CML). METHODS: The clinical data of 118 tyrosine kinase inhibitors (TKIs) resistant Ph(+) ALL and CML cases who were detected ABL kinase domain mutation in Affiliated Tumor Hospital of Zhengzhou University from March 2014 to June 2015 were collected. Karyotypes and BCR-ABL fusion gene were analyzed respectively by R-banding, real-time quantitative polymerase chain reaction (PCR). Total RNA was extracted by TRIzol reagent and ABL kinase domain mutation was detected by direct sequencing. RESULTS: In 23 TKIs resistant Ph(+) ALL and 95 CML cases, the rate of ABL kinase domain mutation was 60.9% (14/23) and 41.1% (39/95), respectively, and the rate of T315I mutation was respectively 34. 8% vs 5.3%, the difference was significant (χ(2)=13.586, P<0.01). The rate of mutations in chronic phase/accelerate phase /blast crisis CML patients was 38.8% (19/49), 47.1% (8/17) and 41.4% (12/29), respectively, and there was no significant difference (χ(2)=0.360, P=0.835). In Ph (+) ALL and CML patients, the median time from the beginning of TKI therapy to appearance of T315I mutation was 10 months and 19 months, the median time from the appearance of T315I to death/deadline was 2 months and 3 months, the median time of persistent hematologic response was 10 months and 16 months and the median time of overall survival (OS) was 13 months and 42 months. CONCLUSION: T315I mutation was more easily occurred in Ph(+) ALL than CML, but two diseases are similar in the median time from the beginning of TKI therapy to appearance of T315I, the median time of persistent hematologic response and OS.