scholarly journals Administration of imatinib after allogeneic hematopoietic stem cell transplantation may improve disease-free survival for patients with Philadelphia chromosome-positive acute lymphobla stic leukemia

2012 ◽  
Vol 5 (1) ◽  
pp. 29 ◽  
Author(s):  
Huan Chen ◽  
Kai-yan Liu ◽  
Lan-ping Xu ◽  
Dai-hong Liu ◽  
Yu-hong Chen ◽  
...  
Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4267-4267
Author(s):  
Xiaoqin Feng ◽  
Zhiyong Peng ◽  
Yuelin He ◽  
Chunfu Li ◽  
Yongsheng Ruan ◽  
...  

OBJECTIVE: Pre-transplant chemotherapy can control progression of primary disease, alleviate disease and improve disease-free survival after transplantation in juvenile granulocyte leukemia (JMML).Methylation abnormalities play an important role in the development of JMML. This study was to explore the effectiveness of induction regimen including decitabine ,cytarabine and fludarabine before transplantation and to explore the affection to transplantation in JMML. METHODS: A retrospective analysis of the remission and survival of 33 children with JMML before and after stem cell transplantation in the Department of Pediatrics of Nanfang Hospital from 2014.2 to 2019.7. There were fourteen girls and 19 boys, median diagnosis age 23 months(2m-10 years old). Median white blood cell count,median hemoglobin level,median platelet count( WBC) was 29.3G/L (6.29-158.66G/L); 83g /L(41-113g/L,); 27.17G / L(4-431G / L) respectively. Median Hemoglobin F level was 34.16%( 1.56-78%). Median spleen level under the costal margin was 5cm(0-13.3cm); Median liver under the costal margin was 3.9 cm(0 -8.9 cm) .There were 26 cases with the pulmonary involvement (26/33, 78.8%). The original blast cells in bone marrow were 0-8.8%, with a median of 4.5%.Mutant genes including: 2 cases of KAS, 9 cases of NF1, 2 cases of NRAS, 16 cases of PTPN11, and 4 cases without common JMML gene .The first course of treatment after diagnosis is 20 mg/m2 × 5 days of decitabine. The second course of treatment is DA: decitabine 20 mg/m2 × 5 days + cytarabine 100 mg/m2 × 5 days or A-3V regimen: Ara-C 100 mg/m2/d CIV×7 days+Etoposide 100 mg/m2/d ×5 days+Vincristine 1.5 mg/m2/d ×1 day. The third course of treatment is decitabine 20 mg/m2 × 5 days,then FLAG regimen: Fludarabine 30mg / m2 × 5 days, Ara-C 1 g / m2 × 5 days, G-CSF 5μg / Kg × 6 days. Single drug of decitabine 20 mg/m2 × 5 days was adminstered 1-3 times per monthly during the period of waiting for transplantation. Comprehensive assessment was performed before transplantation. Survival outcomes were analyzed by Kaplan-Meier curves. RESULTS: At least 3 courses of chemotherapy were completed in 33 cases, including 1-5 courses of decitabine.The bone marrow was evaluated in 31 patients before transplantation: 12 patients got complete remission(CR) and 19 patients got partial remission(PR) .Peripheral blood evaluation: 23 cases achieved WBC CR; 17 cases achieved platelet CR, 6 cases achieved platelet PR, 7 cases had no improvement. Eighteen cases of spleen were evaluated, of which only 3 cases were CR, 13 cases were PR, and 2 cases did not improve. Overall assessment, only 1 case achieved CR before transplantation, 1 case did not improve, and 31 cases achieved PR .Allogeneic hematopoietic stem cell transplantation was performed in 33 cases, including 3 cases of nonrelated peripheral blood hematopoietic stem cell transplantation(PB HSCT), 30 cases of complementary transplantation (haploid identical PB HSCT plus non-related cord blood transplantation). The median follow-up time after transplantation was 22m(3-63m).There was no death in the period of chemotherapy before transplantation. Four patients relapsed after transplantation, and One patient died of transplantation related death. Three years EFS was 80.6%. Conclusion: Pre-transplant chemotherapy based on regimen of decitabine + cytarabine + fludarabine is safe, effective and feasible. The response rate of treatment is 97.0%, although the complete remission rate before transplantation is low, most of them are partial remission, but the disease-free survival after non-related HSCT or complementary transplantation could reached to 80.6%. These results indicated that pre-transplant chemotherapy based on regimen of decitabine + cytarabine + fludarabine was benefit to improved the survival of children with JMML after HSCT. Figure 1 Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5077-5077
Author(s):  
He Huang ◽  
Xiaoyu Lai ◽  
Yi Luo ◽  
Jimin Shi ◽  
Zhen Cai ◽  
...  

Abstract Allogeneic hematopoietic stem cell transplantation (Allo-SCT) has a better anti-leukemic effect than conventional chemotherapy or autologous hematopoietic stem cell transplantation (Auto-SCT) for acute lymphoblastic leukemia (ALL). Large prospective studies on adult ALL showed Allo-SCT would be able to improve disease free survival, and Allo-SCT is currently recommended for patients in first complete remission (CR1), although the role of Allo-SCT for standard-risk ALL patients in CR1 remains controversial. Unrelated donor hematopoietic stem cell transplantation (URD-SCT), considered with higher transplant-related mortality (TRM), is usually not offered to patients in CR1, however, it appears promising now. Over the past few years, improved results of URD-SCT with lower TRM have been reported, reflecting improvements in donor/recipient matching, GVHD prophylaxis, and supportive care. Until now, there were 37 patients with ALL in CR1 received unrelated donor transplantation in our bone marrow transplantation center between July 1999 and April 2007. Philadelphia chromosome occurred in 7 (18.9%) patients at diagnosis. The median age of all patients was 21 years (range 8∼48 years). HLA high-resolution typing was used for donor-recipient matching with 18 cases of HLA-matched and 19 cases of HLA 1–2 alleles mismatched. Graft with a median number of total nucleated cells was 3.43×108/kg (range 2.24∼9.38×108/kg), including CD34+ cells 4.58×106/kg (range 0.96∼9.21×106/kg) and CFU-GM 2.96×105/kg (range 2.15∼6.25×105/kg). All of the patients were received Bu/Cy2 regimen as conditioning with busulfan 16mg/kg plus cyclophosphamide 120mg/kg. Mycophenolate mofetil combined with CsA and short course MTX were performed to prevent aGVHD and 3 patients received additional anti-CD25 monoclonal antibody. The median time to achieve ANC >0.5×109/L was 15 days (range 12∼22 days), platelets >20×109/L was 21 days (range 8∼32 days), and all 37 patients achieved sustained engraftment by the analysis of cytogenetics and STR-DNA. MMF+CsA+MTX could be used as an effective and safe prophylaxis regimen for aGVHD, and incidence of aGVHD was 72.97%, aGVHD of grade I-II observed in 22 (59.46%) patients and the severe aGVHD of grade III-IV observed in 5 (13.51%) patients. The incidence of cGVHD was 58.82%. Early TRM was 8.11% at 100 days after transplant. With a median follow-up of 9.8 months (range 1.0∼79.5 months), clinical relapse were detected in 6 (16.22%) patients and 22 (59.46%) patients achieved disease free survival. By Kaplan-Meier method, the accumulative probability of 3-year overall survival was 59.26±9.18%, and overall survival of Ph(+) ALL was 71.43±17.07%. A strong anti-leukemia effect of GVHD might occur in URD-SCT for ALL, and the 3-year overall surviva was 70.16±11.78% vs 45.00±16.60% in patients with I-II aGVHD or without aGVHD (p=0.0085), which was 76.74±12.52% vs 34.62±14.40% in patients with or without cGVHD (p=0.0015). 4 of 5 patients who developed severe aGVHD died. In our experience of unrelated donor transplantation for ALL in CR1, I-II aGVHD and cGVHD are favorable factors for overall survival, and Bu/Cy2 conditioning regimen could be safely used in the URD-SCT for ALL. Allo-SCT, represents a curative option for ALL, show a significantly increased disease free survival in standard risk or high risk patients in CR1. Unrelated donor transplantation with a greater GVL effect, appears promising for ALL in CR1.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4417-4417
Author(s):  
He Huang ◽  
Yi Luo ◽  
Jimin Shi ◽  
Wanzhuo Xie ◽  
Wenjun Wu ◽  
...  

Abstract Allogeneic hematopoietic stem cell transplantation (alloSCT) is nowadays most frequently applied in patients with acute myeloid leukemia (AML), and it effectively reduces the relapse as its stronger graft-versus-leukemia (GVL) effect, however, the appropriate role and timing of alloSCT in AML are poorly defined. We retrospectively investigated the outcomes of unrelated donor hematopoietic stem cell transplantation (URD-HSCT, n=51; 44 in CR1, 7 beyond CR1) and sibling donor BMT (Sib-HSCT, n=31; 24 in CR1, 7 beyond CR1) for AML between April 1999 and April 2008. The median age of all patients was 27.5 years (range 12–49 years), and HLA high-resolution typing was used for donor-recipient matching with 35 cases of HLA-matched and 16 cases of HLA 1–2 alleles mismatched in URD-HSCT group, while 28 cases of HLA-matched and 3 cases of HLA 1–2 alleles mismatched in Sib-HSCT group. All of the patients were received Bu/Cy or Bu/Cy modified myeloablative conditionging regimen. Mycophenolate mofetil (MMF) combined with CsA and short course MTX were performed to prevent aGVHD and 4 patients in unrelated donor transplant group received additional anti-CD25 monoclonal antibody to prevent severe aGVHD. Hemopoietic recovery and was observed in all patients and the median time to achieve ANC>0.5×109/L was 12.5 days (range 7–22 days), platelets >20×109/L was 15 days (range 9–144 days), and engraftment of neutrophil and platelet did not differ between the two transplant groups. The incidence of aGVHD was significantly higher in URD-HSCT group (54.9% vs 19.4%, p<0.001), however, there was no different of severe aGVHD (13.7% vs 3.2%, p>0.05) and transplant-related mortality (11.8% vs 3.2%, p>0.05) at 100 days between URD-HSCT and Sib-HSCT groups. With a median follow-up of 16.2 months, the 3 years overall survival of the total patients was 73.90±5.11%, and there were no different of disease free survival between AML patients in CR1 and beyond CR1 (69.12% vs 64.29%, p>0.05). Relapse occurred in 15.7% and 9.7% patients following unrelated and sibling donors transplantation respectively, and 3 years disease free survival were 63.85±6.85% and 79.55±7.48% respectively (p>0.05). Based on the data, alloSCT provides a better prospect for cure and would be mostly recommended for patients with AML either in CR1 or beyond CR1, which could be able to improve the leukemia free survival. The outcome of unrelated donor transplantation is comparable to that of sibling donor transplantation for AML. Unrelated donor should be considered in AML patients without a proper sibling donor, especially to patients with unfavorable cytogenetics. MMF combined with CsA and MTX could prevent severe aGVHD efficiently which would reduce the transplant-related mortality in URD-HSCT. At the same time, modifications of supportive care and preparative regimens continue to improve results and extend the application of alloSCT in AML.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1620-1620
Author(s):  
Hong-Hu Zhu ◽  
Ya-Zhen Qin ◽  
Lan-Ping Xu ◽  
Qian Jiang ◽  
Xiao-Hui Zhang ◽  
...  

Abstract [Objective] Previous studies showed that c-KIT mutation and <3log reduction of minimal residual disease (MRD) were two poor prognostic markers for acute myeloid leukemia (AML) with t(8;21) . However, How to deal with c-KIT- mutated t(8;21)AML patients with >3log reduction of MRD remains undefined. To answer this question, we performed this study. [Methods] The current retrospective study consisted of 70 newly diagnosed patients with c-KIT- mutated t(8;21)AML during July 2005 and March 2016 in Peking University People's Hospital. Induction treatment included standard 3+7' regimen or HAA regimen. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) was recommended to all patients with an available donor after 2-3 cycles of consolidation treatment with high-dose cytarabine(HDAC). Patients without a donor or refusing HSCT received HDAC-based intensive treatment. MRD was determined by RUNX1/RUNX1T1 transcript levels detected by Q-PCR. The last follow-up time was July 2016. [Results] Sixty-nine out of 70 patients achieved complete remission(CR).Two patients relapsed after first cycle of consolidation treatment. There were 60 patients having the results of MRD after 2 cycles of consolidation treatment (Figure 1). Thirty-four patients achieved >3log reduction of RUNX1/RUNX1T1 transcript levels (defined as major molecular remission, MMR). There were 16 and 18 patients finally receiving chemotherapy and allo-HSCT. Twenty-six patients did not achieve MMR, and 12 and 14 patients finally receiving chemotherapy and allo-HSCH, respectively. For patients achieving MMR, the 4-year cumulative incidence of relapse (CIR) and disease-free survival (DFS) were 84.8% vs.6.7% (p<0.001) and 20.6% vs.87.5% (p<0.001) when receiving chemotherapy or allo-HSCT(Figure 2). For patients not achieving MMR, the 4-year CIR and DFS were 100% vs.30.8% (p<0.001) and 0% vs.60% (p<0.001) when receiving chemotherapy or allo-HSCT (Figure 2). Multivariate analysis revealed that MRD status (MMR or non-MMR and treatment choice (HSCT or chemotherapy) were independent prognostic factors for relapse, DFS. [Conclusion] We concluded that c-KIT- mutated t(8;21)AML patients with >3log reduction of MRD conferred a very high relapse and need allo-HSCT to improve outcome. Figure 1 The flowchart of the study. Figure 1. The flowchart of the study. Figure 2 Thecumulative incidence of relapse (CIR) and disease-free survival (DFS) of c-KIT mutated t(8;21)AML patients. .. Note : MMR: major molecular remission; CT: chemotherapy. HSCT: hematopoietic stem cell transplantation. Figure 2. Thecumulative incidence of relapse (CIR) and disease-free survival (DFS) of c-KIT mutated t(8;21)AML patients. .. / Note : MMR: major molecular remission; CT: chemotherapy. HSCT: hematopoietic stem cell transplantation. Figure 3 Figure 3. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5132-5132
Author(s):  
Maria Lucia Fuente ◽  
Maria Del Rosario Custidiano ◽  
Santiago Cranco ◽  
Laura Korin ◽  
Paola Ochoa ◽  
...  

BACKGROUND Patients with adverse cytogenetic or secondary AML (s-AML) have significantly worse outcomes and lower survival rates. In this high risk subgroup of patients, early consolidation with allogeneic hematopoietic stem cell transplantation (HSCT) in first complete remission (CR1) can improve results, especially in those who achieve negative measurable residual disease (MRD-). More effective treatments than standard 7+3 are needed. CLAG-M is a salvage regimen that has demonstrated high response rates with good tolerance, and seems to be promising in the upfront setting. AIMS To estimate CR and MRD- rates, overall survival (OS) and event free survival (EFS) in transplant eligible patients with high risk AML treated in our center.To compare CR rate and transplant feasibility in CR1 with 7+3 vs. CLAG-M as induction treatment in s-AML. PATIENTS AND METHODS We analyzed adult patients (18-65 years old) with high risk AML (defined by adverse cytogenetic according to ELN2017 or s-AML) who were treated in our institution between 2010 and 2018. All patients were transplant eligible and had an available donor. Clinical information was collected from medical records. We evaluated CR1 and MRD- rates, EFS and OS. We also compared CR rates and HSCT feasibility in s-AML after treatment induction with CLAG-M and 7+3. The survival analysis was estimated with Kaplan-Meier method and the comparison between variables was performed through log-rank test. RESULTS Twenty-one patients were included (13 s-AML and 8 with adverse cytogenetic). The median age at diagnosis was 54 years (21-64); 13 female/8 male. Out of 21 patients, 14 received 7+3 induction and 7 CLAG-M. The median follow-up time was 11 months (0.9-90.8), median EFS and OS for the whole group was 1.05 and 13.5 months, respectively. Two-year OS was 35%. CR1 was achieved in sixteen patients (76%), 10 of them MRD-. The median time to CR1 was 33 days, the median OS of these patients was 26.7 months (figure 1). Eleven patients (52%) were refractory to first induction, 10/14 in the 7+3 subgroup, and only 1/7 patients treated with CLAG-M. Six of them converted to CR after reinduction (5 with CLAG-M). Fourteen (67%) underwent HSCT in CR1. The median time to HSCT consolidation was 106 days. The median relapse free survival in transplanted patients has not been reached (Table 1). Considering only s-AML, 6 patients received 7+3 and 7 CLAG-M. Median age in 7+3 subgroup was 41 vs. 57 years in CLAG-M. The median OS was 13.5 months. In the 7+3 cohort, only 1 achieved CR (16%); the other five received reinduction with CLAG-M, and 4 converted to CR1. The median time to CR1, EFS and OS were 82 days, 1 month and 26 months respectively. In contrast, 4 of the 7 patients (57%) that received CLAG-M achieved CR1, but only 1 of the 3 that were refractory could convert to CR. The median time to CR1 in patients treated with CLAG-M was 27 days, median EFS 7.5 months and median OS has not been reached (Figure 2). There were no statistically significant differences between the two treatment groups. Eight patients (62%) could be bridged to HSCT, 4 of each subgroup (Table 2). CONCLUSIONS Our results in this real life small cohort of high risk AML were similar to historical controls. In the s-AML subgroup, differences between 7+3 and CLAG-M were not statistically significant probably due to the low number of patients analyzed. However, patients who received CLAG-M required less cycles of treatment to achieved CR1, allowing HSCT rapidly in this selected population. Since most of the refractory patients to 7+3 responded to reinduction with CLAG-M, both groups had similar transplant rates. According to our experience CLAG-M might be an attractive treatment option with high CR rates and acceptable safety profile. In this high risk AML population, two thirds of the patients were effectively "bridged" to HSCT with a 2-year OS rate of 35%. Disclosures No relevant conflicts of interest to declare.


2019 ◽  
Vol 14 (5) ◽  
pp. 719-727 ◽  
Author(s):  
Xianghua Huang ◽  
Wencui Chen ◽  
Guisheng Ren ◽  
Liang Zhao ◽  
Jinzhou Guo ◽  
...  

Background and objectivesOur study evaluated the efficiency and safety of autologous hematopoietic stem cell transplantation treatment for patients with refractory lupus nephritis.Design, setting, participants, & measurementsFrom July 2011 to January 2015, a total of 22 patients with refractory lupus nephritis were enrolled in this study. Peripheral blood stem cells were mobilized with cyclophosphamide and granulocyte colony stimulating factor and reinfused after treatment with cyclophosphamide and antithymocyte globulin. The primary end point was the rate of remission, and secondary end points included the survival and relapse rates, changes in proteinuria, kidney function, and serology immunologic test. All complications were recorded for safety assessment.ResultsTwenty-two patients were enrolled and underwent stem cell mobilization. There were nine men and 13 women, with a median lupus nephritis duration of 46 (33–71) months. The mean number of CD34+ cells was (7.3±3.8)×106/kg. All patients had successful engraftment, and the median times of granulocyte and platelet engraftment were 8 (7–9) and 9 (6–10) days, respectively. The major complications of stem cell transplantation were fever and gastrointestinal tract symptoms. The treatment-related mortality was 5% (one of 22). After a median follow-up of 72 (60–80) months, 18 (82%) patients achieved completed remission, one (5%) patient achieved partial remission, and one patient had no response and received peritoneal dialysis at 12 months after transplantation. The 5-year overall survival and disease-free survival rates were 91% and 53%, respectively. Six patients experienced relapse during the follow-up, and the relapse rate was 27%.ConclusionsAutologous hematopoietic stem cell transplant could be used as a treatment option for refractory lupus nephritis, because it was relatively safe and associated with good outcomes.


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