Efficacy and Prognostic Factors of Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To retrospectively analyze the efficacy and complications of our institution's modified nonmyeloablative allogeneic hematopoietic stem cell transplantation (NST) in treating intermediate-risk acute myeloid leukemia (AML) - first complete remission (CR1) and prognostic factors.@*METHODS@#Clinical data of 50 intermediate-risk AML-CR1 patients who underwent matched related NST at the Fifth Medical Center of Chinese People's Liberation Army General Hospital from August 2004 to April 2021 were collected, the hematopoietic recovery, donor engraftment and complications were observed, and overall survival (OS) rate, leukemia-free survival (LFS) rate, treatment-related mortality (TRM), and cumulative relapse rate were calculated. Statistical analysis of factors affecting prognosis was also preformed.@*RESULTS@#The median times for neutrophil and platelet recovery after transplantation were 10 (6-16) and 13 (6-33) days, respectively. One month after transplantation, 22 patients (44%) achieved full donor chimerism (FDC), and 22 patients (44%) achieved mixed chimerism (MC), among whom 18 cases gradually transited to FDC during 1-11 months, 4 cases maintained MC status. The overall incidence of acute graft-versus-host disease (aGVHD) was 36%, with a rate of 18% for grade II-IV aGVHD and a median onset time of 45 (20-70) days after transplantation. The overall incidence of chronic GVHD (cGVHD) was 34%, with 20% and 14% of patients having limited or extensive cGVHD, respectively. The incidence rates of infections, interstitial pneumonia, and hemorrhagic cystitis were 30%, 10%, and 16%, respectively. The 5-year OS rate, LFS rate, TRM, and cumulative relapse rate were 68%, 64%, 16%, and 20%, respectively. The increase of the number of CD34+ cells infused had shortened the recovery time for neutrophils and platelets (r =0.563, r =0.350). The number of CD34+ cells infused significantly influenced the occurrence of extensive cGVHD (OR =1.36, 95%CI : 1.06-1.84, P =0.024).@*CONCLUSION@#Modified NST is effective in treating intermediate-risk AML-CR1 patients, however, further expansion of sample size is needed to study prognostic factors.

Significance of Monitoring Minimal Residual Disease by Flow Cytometry in Acute Leukemia Patients Underwent Nonmyeloablative Allo-HSCT / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the value of dynamically monitoring minimal residual disease (MRD) by flow cytometry before and after non-myeloablative allo-HSCT (NST) for prediction of acute leukemia(AL) relapse after transplantation.</p><p><b>METHODS</b>The clinical data of 51 AL patients underwent NST were analyzed retrospectively in Department of Hematology of Affiliated Hospital of Academy of Military Medical Sciences from January 2011 to December 2015. All AL patients achieved the morphologic complete remission of bone marrow before transplantation. The bone marrow samples were collected for monitoring of MRD within 35 days before transplant, every month till 3 months after transplant, every 3 months till 24 months after transplant, and then every 6 months after 2 years of transplant. According to the MRD cutoff value of 0.2%, the AL patients were divided into high level MRD group (18 cases) which was defined as MRD≥0.2% after transplantantion at least for 1 time, and low level MRD group (33 cases) which was defined as MRD<0.2% after transplant all the time. 2 year cumulative relapse rate in 2 groups were compared.</p><p><b>RESULTS</b>Two-year relapse rates were 6.1% and 50% in low-level MRD group and high-level MRD group post NST(P=0.001)respectively. Multivariate analysis indicated that the risk of relapse in high level MRD group was 5.84 times of low level MRD group(P=0.036). MRD≥0.2% post transplant was an independent risk factor for leukemia relapse post NST. The mortality rate was 81.8% and 46.3%(P<0.05) in relapse and non-relapse groups respectively.</p><p><b>CONCLUSION</b>Dynamically monitoring MRD by FCM is a crucial tool for early relapse estimation of acute leukemia in adult patients after allogeneic nonmyeloablative hematopoietic stem cell transplantation. MRD≥0.2% after transplant can be used as a early valuable evidence for predicting relapse and guiding active medical intervention.</p>

Features of Immunophenotypes and Characteristics of Molecular Biology and Cellular Genetics of AML Patients with CD4 and CD7 Expression / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the features of immunophenotypes and the characteristics of molecular biology and cellular genetics of AML patients with CD7 and CD4 expression.</p><p><b>METHODS</b>The immunophenotypical markers of AML cells were detected by multiple parameter flow cytometry; the expression of WT1, MDK, ETO, PML-RaRa and BCR-ABL were detected by RT-PCR; and cellular features were analyzed by R-band in 304 patients. The patients were divided into three groups according to their immunophenotypes: AML with CD7 expression (CD7 group), AML with CD4 expression(CD4 group) and AML without CD7 and CD4 expression (common AML group).</p><p><b>RESULTS</b>The expression rate and level of HLA-DR in CD7 group were higher than those in the common AML group, and the expression rate of CD33 and CD34 was higher than that in the other two groups. The expression rate and level of CD15, CD64 in the CD4 group were higher than those in the other 2 groups, and the expression rate and level of CD33 were higher than those in the common AML group. WT1 expression in the CD7 group was lower than that in the common AML group. PML-RaRa was not detected in the CD7 group. AML with co-expression of CD4 or CD7 showed more normal karyotype. (15;17) was not found in AML with CD7 expression.</p><p><b>CONCLUSION</b>AML cells with CD7 expression originate from precursor cells and are blocked in the early phase of hematological development; AML cells with CD4 expression originate from more mature stage of hematological devevelopment and with CD33, CD64 and CD15 high expression; AML cells with CD7 and CD4 expression are characterized by no-specific change of cellular genetics. According to the expression level and intesity of CD4 and CD7, and together with other specific lineage markers, the MRD in AML patients can be quantitatively detected.</p>

Expression of WT1 Gene in Bone Marrow of Patients with Acute Myeloid Leukemia and Its Influence on Prognosis / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the expression level of WT1 gene in bone marrow of patients with acute myeloid leukemia (AML) and its relationship with prognosis.</p><p><b>METHODS</b>The copy numbers of WT1 and internal reference gene in bone marrow samples from 75 newly diagnosed AML patients were detected by using real-time quantitative PCR. The gene WT1 expression level was determined by the ratio of the copy numbers of WT1 to reference gene. And the clinical characteristics, the complete remission (CR) rate after induction chemotherapy, 2-year overall survival (OS) rate and event-free survival (EFS) rate were calculated and analysed.</p><p><b>RESULTS</b>The expression level of WT1 did not significantly correlate with common clinical parameters such as age, sex, molecular abnormality, FAB classification and risk stratification. The CR rate in the high WT1 expression group before treatment was 65.4%, which was lower than that of 93.9% in the low expression group (χ2=8.25, P<0.01). The 2-year overall survival rate and event-free survival rate of the two groups were statistically significantly different (P<0.05), and the OS and EFS rates in high WT1 expression group were lower than those in low expression group. After the induction chamotheropy for about 1, 3 month and 6 months, the 2-year OS rate significantly increased in patients with decrease of WT1 gene expression level by one log or more (P<0.05).</p><p><b>CONCLUSION</b>The expression level of WT1 gene in bone marrow may be an effective marker to evaluate therapy efficacy and prognosis for AML patients (non APL).</p>

Characteristics and Prognosis of 24 Cases of Primary Acute Myeloid Leukemia with Trisomy 8 / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the clinical features and prognosis of primary acute myeloid leukemia (AML) with trisomy 8.</p><p><b>METHODS</b>The clinical data of 24 cases diagnosed as primary AML with trisomy 8 were collected. The clinical characteristics such as sex, age, subtype of FAB, blood routine and bone marrow blast at the first visit were analyzed and the relationship of the characteristics with CR rate and the prognosis was explored.</p><p><b>RESULTS</b>12 out of 24 AML patients were diagnosed as M5 (50%), while M2, M3, M4 and M6 had 3 cases, respectively (12.5%); one case did not receive the chemotherapy. 23 cases received 1-2 cycles of standard induction chemotherapy. Among them 3 cases of M3 achieved complete response (CR) and survived until the last following up with 100% 5-year OS rate. Among 20 cases of non-M3, 12 cases achieved CR1 (60%), 4 cases achieved partial response (PR) (20%), 4 cases did not respond (NR); 5 cases relapsed in follow-up for 3 years after CR1 (41.7%), 3 cases achieved CR2 after re-induction chemotherapy, and 2 cases remained NR. Among 20 cases of non-M3, 1 case failed to be followed-up after diagnosis within 1 month. The mean follow-up time of 19 cases was 26.2 (1.5-84) months, 9 cases died (6 cases of M5, 1 case of M4 and 2 cases of M2), who achieved PR and NR, or relapsed after CR1; the 3-year DFS and OS were 21%, 31.5% respectively. 2 cases of non-M3 accepted allo-HSCT with HLA-matched sibling donor and kept disease-free survival until the last following up, and survived for 58 and 66 months respectively. Except for 3 cases of M3, 2 cases received allo-HSCT and the cases without chemotherapy, the other 18 cases with initial WBC count less than 10×10(9)/L had OS and DFS longer than those of 10 cases with initial WBC count no less than 10×10(9)/L (P<0.05, P<0.01). The OS of 10 cases with CR1 was longer than OS of those cases without CR1 (P<0.01).</p><p><b>CONCLUSION</b>The incidence of trisomy 8 in M5 is higher than the other AML subtypes, and the prognosis of M5 is poor. The initial WBC count above 10×10(9)/L is a high-risk factor. M3 with trisomy 8 and RARA gene has a very good prognosis. Trisomy 8 may increase the risk of primary AML except for M3, so allo-HSCT with HLA-matched sibling donor should be carried out as much as possible after CR1. The gene mutation of FLT3, MLL, HOX11, C-kit, NPM1 may possess an important significance on prognosis.</p>

Clinical efficacy of switching to 2nd generation of tyrosine kinase inhibitor on CML patients at poor responses to imatinib / 中国实验血液学杂志

<p><b>OBJECTIVE</b>This study was to investigate the timing and clinical efficacy of switching to the 2nd generation of tyrosine kinase inhibitor (TKI) for CML patients at poor response to imatinib (dissatifed efficacy or intolerance).</p><p><b>METHODS</b>The therapeatic efficacy and side reaction of switched 2nd TKI in patients with newly diagnsed CML-CP who poorly responded to imatinib were observed, anong them 3 cases were intolerant, 6 cases did not acquire satisfied efficacy.</p><p><b>RESULTS</b>After switching to 2nd generation TKI, 3 patients with intolerance achieved complete cytogenetic remission (CCyR) in 3 months, and major molecular remission (MMR) in 3-6 months. All of them achieved optimal efficacy according to European Leukemia Network (ELN), but the pleural effusion appeared in 1 case after use of 2nd generation of TKI for 3 months, and the dadatinib was stoped temporally, and the curative efficacy still was maintained. Among 6 cases with poor efficacy by treatment with imatinib, 2 cases with BCR/ABL mutation progressed after switching 2nd generation of TKI, out of them 1 case with poor tolerance progeressed to the accelerated phase, but was cured by haploidentical allogeneic hematopoictic stem cell transplantation, 1 case progressed to blastic crisis and died of serious infection; the another 4 cases achieved MMR in 3-12 months after using 2nd generation of TKI, and maintained CMR for 12-36 months.</p><p><b>CONCLUSION</b>CML-CP patients without the optimal response to imatinib should be treated by switching to 2nd generation of TKI as soon as possible, and thereby patients may acquired satisfactory therapentic efficacy.</p>