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Acute lymphoblastic leukemia (ALL) is a malignancy originating from B-/T-lineage lymphoid progenitor cells. With the continuous development of new drugs as well as therapeutic regimens, adult ALL patients have improved complete remission rates and overall survival rates, but the survival rate of patients after relapse remains low. The positive minimal residual disease after complete remission is an important reason for relapse. Although minimal residual disease monitoring has been found to be important in predicting patients prognosis in recent years, the uniform stratified treatment protocols have not yet been developed in the clinical practice of adult ALL. This article reviews the prognostic significance of minimal residual disease monitoring at different time points, as well as the progress of removal methods of minimal residual disease.
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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the main curable therapies for patients with acute lymphoblastic leukemia (ALL). This article discusses the status of allo-HSCT for ALL as well as how to combine targeted therapy with allo-HSCT to improve outcomes of ALL in the era of targeted therapy based on the data obtained from the 63rd American Society of Hematology (ASH) Annual Meeting.
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Objective:To explore the early identification, diagnosis and pathogenesis of childhood acute lymphoblastic leukemia (ALL) complicated with cytokine release syndrome(CRS).Methods:The clinical data of childhood ALL complicated with CRS admitted to Shenzhen Children's Hospital in February 2021 were retrospectively analyzed. The relevant literature was reviewed.Results:The little girl was 2 months and 11 days of age and was diagnosed with ALL with MLL rearrangement positive by bone marrow aspiration because of abdominal mass and abnormal hemogram. She had recurrent high fever with pulmonary imaging characteristic changes during the early intensive induction chemotherapy, accompanied by the elevated interlukin (IL)-2, IL-6, IL-10 and interferon (IFN)-γ. Finally, she was diagnosed with ALL complicated with CRS. Glucocorticoid therapy showed a good efficacy and her clinical symptoms improved.Conclusions:ALL complicated with CRS is essentially induced by cytarabine syndrome drugs in the chemotherapy. The main clinical manifestations include recurrent high fever accompanied by the elevated IL-2, IL-6, IL-10 and IFN-γ. The symptomatic and supportive therapy is usually based on glucocorticoids. Early identification and diagnosis can reduce adverse drug reactions and improve the life quality of children.
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Objective To investigate the efficacy and safety of maintenance treatment with low-dose decitabine after allogeneic stem cell transplantation (allo-HSCT) for high-risk acute lymphoblastic leukemia (ALL). Methods The data of 10 patients with high-risk ALL who received maintenance therapy with low-dose decitabine after allo-HSCT in the First Affiliated Hospital of Zhengzhou University from July 2016 to March 2018 was collected. The incidence of post-transplant relapse and graft-versus-host disease (GVHD) and the safety of the treatment protocol were analyzed. The cumulative incidence of relapse (CIR) rate, disease-free survival (DFS) rate and overall survival (OS) rate were estimated by Kaplan-Meier method. Results Two patients relapsed and the median relapse time of these 10 patients was 575 days after transplantation. The 1-year CIR, OS and DSF rates were 16.7%, 100.0% and 83.3%, respectively. At the end of follow-up, the DFS time after transplantation of 2 patients with p53 mutation were 23 months and 11 months, respectively. There was no induction or alleviation of GVHD caused by decitabine treatment. Nine patients developed grade Ⅰ-Ⅱmyelosuppression. Three patients had unexplained thrombocytopenia after transplantation and their platelet counts recovered after decitabine treatment. Conclusion Maintenance therapy with low-dose decitabine has low hematologic toxicity without increasing GVHD, which could be a maintenance treatment option to prevent relapse after transplantation for patients with high-risk ALL.
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Objective@#To investigate the clinical effect and safety of dasatinib combined with Chinese Children's Leukemia Group-acute lymphoblastic leukemia (CCLG-ALL) 2008 protocol in treatment of childhood Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL).@*Methods@#The clinical data of 22 patients with Ph+ ALL who were newly diagnosed at the age of less than 15 years old in Fujian Medical University Union Hospital from January 2014 to December 2018 were retrospectively analyzed. All patients were treated with dasatinib combined with CCLG-ALL2008 protocol (high-risk group). The patients were assigned to two groups according to different starting times of oral dasatinib: the dasatinib-induced group (starting from day 15 of induction chemotherapy) and the dasatinib-consolidated group (starting with early consolidated chemotherapy). The early treatment response and 5-year event-free survival (EFS) rate were compared between the two groups.@*Results@#The differences of clinical characteristics and early efficacy of chemotherapy before treatment of dasatinib between the two groups were not statistically significant (both P > 0.05). The complete remission (CR) rate on day 33 of induction chemotherapy was higher in the dasatinib-induced group than that in the dasatinib-consolidated group [100% (10/10) vs. 75% (9/12)], but the difference was not statistically significant (χ 2= 2.895, P= 0.221). The rate of minimal residual disease (MRD) turned negative (<0.01%) on day 33 of induction chemotherapy in the dasatinib-induced group was significantly higher than that in the dasatinib-consolidated group [70% (7/10) vs. 17% (2/12)], and the difference was statistically significant (χ 2= 6.418, P= 0.027). The 3-year EFS rate was higher in the dasatinib-induced group than that in the dasatinib-consolidated group (88.9% vs. 63.5%), but the difference was not statistically significant (P= 0.163). The incidence of grade 3-4 infection in the dashatinib-induced group was lower than that in the dasatinib-consolidated group, and the difference was statistically significant [60% (6/10) vs. 100% (12/12), P= 0.029]. the other grade 3-4 adverse reactions related to the chemotherapy drugs mainly included hematological toxicity, diarrhea, abnormal liver function, edema and pleural effusion, but there was no significant difference between the two groups (all P > 0.05).@*Conclusions@#Dasatinib combined with CCLG-ALL2008 protocol in the treatment of children with Ph+ ALL has good efficacy and safety. Furthermore, the early use of dasatinib on day 15 of induction chemotherapy can enable patients to achieve deeper remission earlier and improve long-term efficacy.
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Objective To improve the understanding of the diagnosis and treatment of Philadelphia (Ph) chromosome-like acute lymphoblastic leukemia (ALL) with EBF1-PDGFRB-positive. Methods One case of Ph-like ALL with EBF1-PDGFRB-positive from the First Affiliated Hospital of Soochow University was reported. Whole exome sequencing was applied to detect the EBF1-PDGFRB fusion gene. Fluorescence in situ hybridization (FISH) was used to detect minimal residual disease. Comprehensive treatments including chemotherapy, imatinib and chimeric antigen T-cell (CAR-T) therapy were utilized. Results EBF1-PDGFRB fusion gene in the bone marrow samples was detected by using whole exome sequencing at early diagnosis. The rearrangement of PDGFRB showed continuous negative after comprehensive therapy. The patient achieved continuous molecular remission for 22 months. Conclusions The comprehensive treatments include combined chemotherapy, CAR-T therapy and tyrosine kinase inhibitor can promote the continuous of major molecular remission for EBF1-PDGFRB-positive Ph-like ALL patients.
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Objective@#To investigate the clinical significance of monitoring ETV6-RUNX1 fusion gene in children with acute lymphoblastic leukemia (ALL) after allogeneic stem cell transplantation (allo-HSCT) .@*Methods@#Clinical data of 13 children received allo-HSCT in Peking University Institute of Hematology from May 2009 to March 2016 were retrospectively collected. The ETV6-RUNX1 gene was examined by real-time quantitative polymerase chain reaction (RQ-PCR) . The correlation between its expression level and the disease status was analyzed.@*Results@#Of 13 enrolled ALL cases, the ETV6-RUNX1 expression of 7 patients converted to positive after transplant at a median time of 137 days (range, 28-270 days) . The expression level of the first positive sample was 0.034% (range, 0.004%-0.061%) . The duration from ETV6-RUNX1 positive to hematological relapse was 196 days (range, 28-666 days) . Four patients experienced relapse at a median time of 294 days (range, 104-803 days) after allo-HSCT. The ETV6-RUNX1 expression converted to positive prior to MRD. Patients with positive ETV6-RUNX1 gene expression pre-transplantation would be more likely to relapse.@*Conclusion@#Monitoring ETV6-RUNX1 by RQ-PCR could be used to evaluate MRD status after allo-HSCT. Patients with positive ETV6-RUNX1 after transplant had a poor prognosis.
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Objective@#To investigate the current status of catheter-related-thrombosis (CRT) and the risk factors of Chinese acute lymphocytic leukemia (ALL) children with peripherally inserted central catheter (PICC) .@*Methods@#The clinical data of the 116 inpatients preliminarily diagnosed ALL in the Leukemia Ward of Beijing Children’s Hospital with PICC from 1st March 2014 to 31st December 2014 were collected prospectively.@*Results@#①Refer to the B-ultrasound on the 15th day after catheterization, the incidence of CRT was 28.4% (33/116 cases) , all cases were symptom-free. ②There were no statistical differences in terms of gender, age distribution, degree, immunotype between CRT and CRT-free groups. This study revealed no statistical differences of blood routine test items, coagulation function items, co-infection and catheterization vein between the two groups. While there was significant statistical difference of catheterization side, the frequency of right catheterization was higher in CRT group[75.8% (25/33) vs 55.4% (46/83) , P=0.043]. ③On the 15th day after catheterization, significant statistical difference of D-Dimer between the two groups was revealed[0.18 (0.05-2.45) mg/L vs 0.11 (0.01-5.34) mg/L, P=0.001], while no statistical differences of blood routine test items and other coagulation function items. Multivariate Logistic regression analysis verified catheterization on right was a risk factor of CRT. ④During the observation, there were 3 cases of catheter-related complications other than CRT, all of which were CRI, 2 of them had CRT meanwhile. ⑤The B-ultrasound on the 33rd day after catheterization showed that 73.1% of the cases had reduced thrombosis, 3.8% had growth thrombosis, 23.1% had no obvious change respectively.@*Conclusion@#CRT was a common catheter related complication among ALL children during induction chemotherapy, and CRT cases with symptoms were rare. Catheterization on right was a risk factor for CRT, and regular test of D-Dimer and B ultrasound contributed to detect CRT. Most of the CRT cases had reduced thrombosis without specific management.
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Objective To investigate the efficacy and prognostic risk factors of ALL-R-2003 protocol in the treatment of relapsed childhood relapsed acute lymphoblastic leukemia (ALL) in single center. Methods A retrospective study of clinical data of 51 children with relapsed ALL from January 2004 to December 2014 was performed by using SPSS version 19.0 statistical software for statistical analysis. Results The median age at initial diagnosis of 51 patients was 5.5 years (range, 0.8-13.4 years). The median time from initial diagnosis to relapse was 25 months (range, 3-68 months) and follow-up time was 39 months (range, 3-116 months). The relapse rate in the standard-risk, intermediate-risk and the high-risk groups were 27.5 % (14/51), 29.4 %(15/51) and 43.1 % (22/51), respectively. The probability of 3-year overall survival (pOS) after relapse was (18.8±5.9)%and the probability of event free survival (pEFS) was (16.2±5.8)%. The 3-year pOS in very early relapse, early relapse and late relapse were 0, (11.7 ±7.7) % and (51.7 ±14.8) %, respectively (P= 0.000). There was no statistical difference in survival rate of different immunophenotype groups and sites of relapse (P> 0.05). The 3-year pOS of group S1, S2, S3, S4 were (50.0±35.4) %, (39.9±1.3) %, (10.0±9.5) % and 0, respectively (P=0.000). The 3-year pOS of bcr-abl and MLL gene positive groups were (25.0±21.7) %and 0, respectively, with no statistically significance compared with the negtive group [(24.1±12.0)%] (P>0.05). The 3-year pOS rates of children with bone marrow transplantation and without transplantation were (40.0 ±15.5) %and (13.0 ±5.9) % respectively (P= 0.038). Conclusions The children who in high risk group at initial diagnose are easily to meet earlier relapse and poorer prognosis. The survival period after relapse of bcr-abl or MLL gene positive cases is very short. Bone marrow transplantation can improve survival rate. Risk group at initial diagnose, relapse time and transplantation are the main factors influencing prognosis, and the relapse time and transplantation are the independent prognostic factors for relapsed childhood ALL.
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Objective To explore the efficacy and safety of high-dose methotrexate (MTX) and L-asparaginase (L-Asp) for the treatment of adult patients with high risk Ph acute lymphoblastic leukemia (ALL).Methods Five adult patients with high risk Ph-ALL were treated with several courses of MTX (3-5 g/m2 by continually intravenous drip for 24 h) and L-Asp (8 000-10 000 U/time, once a day, 10 times for one cycle).Results Five patients were disease-free survival, their survival time was 60-96 months and the median survival time was 73 months.The chemotherapy-related bone marrow depression was mild.No obvious liver and kidney damage, severe allergic reaction and pancreatitis were observed.Conclusion Highdose MTX and L-Asp are effective and well tolerated, and may contribute to long-term survival of adult patients with high risk Ph-ALL.
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Outcome of patients with adult acute lymphoblastic leukemia (ALL) is poor,and even worse among patients with relapsed/refractory ALL (R/R ALL).New treatments must be taken to overcome drugresistance to conventional chemotherapy for ALL.Humanized monoclonal antibody and chimeric antigen receptor gene modified T cells have become the focus of treatment in ALL.Lots of clinical trials in multiple research centers are in progress,and the results constantly upgrade which is effectively bring better curative effect and prognosis for R/R ALL patients.This is one of the hot topics at the 56th ASH annual meeting.
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Humanized monoclonal antibody and CARs have became the focus of treatment in adult acute lymphoblastic leukemia (ALL) at the 55th ASH annual meeting.Treating with chemotherapy plus monoclonal antibody will get a develop effect in relapse/refractory adult ALL.More immune-pharmaceutics will be used in clinical trials.
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Objective To analyze the clinical features of pediatric patients with acute lymphoblastic leukemia(ALL) with bcr-abl fusion gene transcript,and discuss the treatment,prognosis factors of this kind of ALL.Methods Clinical features,treatment and prognosis were studied retrospectively in 7 bcr-abl fusion gene positive ALL patients.bcr-abl fusion gene was detected by reverse transcription polymerase chain reaction (RT-PCR).Results The average age of the 7 patients was 8 years and 1 month old.All of them were common B-immunology ALL.The rate of complete response was 50 ％ after 33 days' treatment.Conclusions The incidence rate of bcr-abl fusion gene positive ALL in pediatric is low.This type of ALL has poor remission,high relapse rate and poor prognosis.
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Objective To study the molecular mechanism of berberine induced apoptosis in chemoresistant EU-4 acute lymphocytic leukemia cells.Methods EU-4 cells were treated with 0,10 and 100 μmol/L berberine for 72 h.The apoptosis induced by berberine was detected by flow cytometry.The expression of Caspase-3,PARP and X-linked inhibitor of apoptosis protein (XIAP) were determined by Western bolt assay.Caspase-3 activity was measured using microplate reader.After transfected with XIAP siRNA,the apoptosis was detected by flow cytometry.Results After treated with 0,10 and 100 μmol/L berberine for 72 h,the apoptosis rates of EU-4 cells were (9.08±1.20) ％,(22.36±2.16) ％ and (59.81±4.17) ％,respectively.Berberine induced potent apoptosis in a dose-dependent manner.The apoptosis involved activation of Caspase-3.The Caspase-3 activities were 1.70±0.25,1.92±0.10 and 2.89±0.25,respectively.Berberine inhibited XIAP expression in a dose-and time-dependent manner (P ＜ 0.05).Down-regulation of XIAP by siRNA increased apoptosis of EU-4 cells.The apoptosis rates were (9.23±1.66) ％ and (22.15±0.63) ％.Conclusion Berberine could induce apoptosis of EU-4 cells,and inhibition of XIAP leading to Caspase-3 activation is responsible for the apoptotic effect on EU-4 cells.
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Objective To investigate the chromosome karyotype of acute lymphocytic leukemia (ALL) and its correlation with the clinical feature and efficacy.Methods The chromosomes of bone marrow/peripheral blood from 110 cases of patients with ALL were prepared after 24 hours culture,and G-banding were used to analyze karyotypes.Results Among 110 patients with ALL,71 cases (64.5 ％) had clonal chromsomal normalities,39 cases (35.5 ％) had clonal chromsomal abnormalities,24 cases (21.8 ％) had chromosome structural abnormalities,11 cases (10.0 ％) had chromosome number abnormalities,3 cases (2.7 ％) had chromosome number and structure abnormalities,one case had chromosomal abnormalities complex karyotype.Efficacy in patients with ALL with t(9;22) (q34;q11) was worse than the other patients (Fisher s exact text,P =0.045).There was no significant difference on efficacy between in adult ALL associated with t(9;22) (q34;q11) and in children with ALL (Fisher's exact text,P =0.506).Conclusion Chromosome karyotype of ALL patients is random,chromosomal translocations such as t(9;22)(q34;q1 1) and t(4;11) (q21;q23) have poorer treatment outcomes.
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Objective To investigate the relation between demethylation effect and apoptosis of valproate (VPA) in primary acute lymphoblastic leukemia (ALL) cells in vitro.Methods 10 cases of ALL patients was choosed to acquire leukemia cells.Cell growth curve were assessed by the MTT assay,the apoptosist of primary ALL was analyzed with DNA Ladder and Annexin-V-FITC/PI by flow cytometry.The expression methylation level of p15 was detected by hn-MSPCR,and p15mRNA were detected by RT-PCR.All dates was analyzed by SPSS16.0.Results The 50 ％ inhibition rate of VPA were 1.898 mmol/L to primary ALL cells assayed by MTT respectively.DNA ladder showed the apoptosis of primary ALL cells increased by adding VPA dose.Annexin-V-FITC/PI tests showed that the apoptosis percentage of primary ALL cells were (0.44±0.04) ％ in control group,(5.80±0.65) ％ in 1.0 mmol/L VPA group,(48.46±2.49) ％ in 2.0 mmol/L VPA group,(76.45±2.98) ％ in 4.0 mmol/L VPA group,the apoptosis percentage increased significantly (P ＜ 0.05).The demethylation of p15 INK4B gene decreased by adding VPA dose,the expression of p15 mRNA expression increased significantly compared with control group by RT-PCR (P ＜ 0.05).Conclusion It is found that VPA could induce demethylation of p15 INK4B gene,which could upregulate the p15 mRNA expression,due to the apoptosis of primary ALL cells.
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Objective To investigate the expression of myeloid antigen(MyAg) in acute lymphoblastic leukemia (ALL) and its correlation with clinical characteristics and prognosis.Methods The clinical data of 103 newly diagnosed ALL 1patients were retrospectively analyzed.These patients were divided into myeloid antigen-positive group (MyAg+ ALL) and myeloid antigen-negative group(MyAgALL) based on the flow cytometry(FCM) analysis in bone marrow.The correlation of MyAg expression with the clinical features,short-term efficacy and 5-year overall survival were assessed in the two groups.Results MyAg expression was detected in 46.5％ out of 103 cases and CD13,CD33 were the most commonly expressed MyAg(34.2％ and 21.4％ respectively).The expression of CD34 in MyAg+ ALL group was higher than MyAgALL group(75.3％ vs 60.5％,P ＜0.05).The expression of MyAg in T-ALL group (66.7％) was higher than B-ALL group (42.8％) (P ＜ 0.05).The clinical and biological characteristics of ALL patients between MyAg+ and MyAggroups showed that higher percentage of incoincidence of classification between morphology and immunology.Conclusion MyAg expression was not correlated with clinical characteristics and prognosis of ALL patients.
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Objective To investigate the relationship between genetic polymorphism of methylenetetrahydrofolate reductase (MTHFR) and the risk of childhood acute lymphocytic leukemia (ALL).Methods 45 patients with ALL and a cohort of 45 matched healthy children were included,and DNA was extracted from their peripheral blood.PCR-RFLP was used to determine the genotypes of MTHFR C677T and A1298C.The adjusted odds tatio (OR) and 95 ％ confidence interwal (CI) were calculated using unconditional logistic regression model.Results The frequency of MTHFR 677 CC,CT and TT genetypes were 31.1％ (14/45),51.1％ (23/45) and 17.7 ％ (8/45) in controls and 51.1％ (23/45),40.0 ％ (18/45) and 8.9 ％ (4/45)in ALL,respectively (x2 =7.48,P =0.04).The frequency of MTHFR 677 T allele were 69.9 ％ (31/45) in controls and 48.8 ％ (22/45) in ALL.The MTHFR 677 T allele had an decreased risk in ALL compared with CC genetype (OR =0.4,95 ％ CI 0.21-0.83).The frequency of MTHFR 1298 AA,AC and CC genetypes were 57.8 ％,40.0 ％ and 2.2 ％ in controls and 18.8 ％,44.4 ％ and 6.8 ％ in ALL,respectively (x2 =11.23,P=0.23).The frequency of MTHFR 1298 C allele were 51.1％ (23/45) in controls and 42.2 ％ (19/45) in ALL.No significant association between the MTHFR 1298 polymorphism and the risk of ALL (OR =1.3,95 ％ CI 0.21-0.83).Conclusion MTHFR 677 polymorphism could significantly decrease the risk of developing childhood ALL,whereas MTHFR 1298 don' t significantly affect the risk of ALL.
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Objective To analyze the treatment efficacy and safety of a modified GMALL protocol for adult acute lymphoblastic leukemia (ALL). Methods Data of 37 patients with newly diagnosed adult ALL treated with a modified GMALL protocol from January 2005 to December 2009 were retrospectively analyzed,and compared with that of 44 patients treated with an in-house conventional protocol at the same period.Results The complete remission (CR) rate was 89.2 %(33/37) treated with modified GMALL protocol. The cumulative overall survival (OS) rates at 1 year, 2 years, 3 years and 4 years were 77.5 %, 48.0 %, 40.0 %and 40.0 %, respectively. The main adverse events were grade 3 or grade 4 hematological toxicities and infections which were easily managed, and the treatment-related mortality rate was low. The OS of modified GMALL protocol was superior to that of the conventional protocol. Conclusion The modified GMALL protocol has a satisfying effect and the adverse events can be tolerated for adult ALL, so its clinical application can be encouraged.
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Objective To analyze the outcomes and the prognostic factors of hematopoietic stem cell transplantation (HSCT) in combination with imatinib for Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Methods All 32 patients with Ph+ ALL achieved hematologic complete remission (CR) at time of transplantation, including 27 cases in the first CR (CR1) and 5 in CR2. Nineteen patients achieved molecular remission (MR). Among 32 patients, 4 received autologous HSCT (AHSCT), and 28 allogeneic HSCT (allo-HSCT). The conditioning regimens comprised of total body irradiation (TBI), cyclophosphamide, fludarabine and cytarabine. The median number of transfused mononuclear cells was 5. 6 × 108/kg, and that of CD34+ cells was 2. 94 × 106 /kg. Thirty-one patients were administrated imatinib orally before transplantion, at a dose of 400～600 mg/day, and 16 patients after transplantation, including 7 for prevention at a dose of 300～400 mg/day and 9 for salvage treatment at a dose of 400 ～ 600 mg/day. Results Hematopoietic reconstitution was achieved in all 32 patients. Three-year estimate of overall survival (OS) was (62. 1±8. 6)%, leukemia-free survival (LFS) (59. 2 ± 8. 7)%, relapse rate (RR) (17. 7 ± 7. 2)% and transplant-related mortality (26. 2 ± 8. 0) %. All 4 undergoing AHSCT were alive, and 3 out of them were in continuous CR with durations of 14, 18 and 67 months respectively. The univariate analysis for prognosis in allo-HSCT showed that the OS of HLA-matched sibling donors group was 76. 5 %,higher than that of unrelated or haploidentical donors group (27. 3 %, P＜0. 05), and so was LFS (70. 6 % vs 27. 3 %, P＜0. 05). RR in patients achieving MR at time of transplantation was 5. 6 %,lower than that in those not achieving MR (40. 0 %, P＜0. 05). RR in patients in CR1 at time of transplantation was 12. 5 %, lower than that in those in CR2 (50 %, P ＜0. 05). Conclusion Imatinib improved the outcomes of HSCT for Ph+ ALL, especially to patients achieving MR at time of transplantation and transplantation in early stage (CR1).