Cytology or Multiparameter Flow Cytometry Positivity in the Cerebrospinal Fluid Before Transplantation is Predictive of Poor Outcomes After Allotransplantation in Acute Myeloid Leukemia Patients.

INTRODUCTION: Central nervous system leukemia (CNSL) remains a serious complication in patients with acute myeloid leukemia (AML) and an ambiguous prognostic factor for those receiving allo-geneic hematopoiesis stem cell transplantation (allo-HSCT). It is unknown whether using more sensitive tools, such as multiparameter flow cytometry (MFC), to detect blasts in the cerebrospinal fluid (CSF) would have an impact on outcome. METHODS: We retrospectively analyzed the clinical outcomes of 1472 AML patients with or without cytology or MFC positivity in the CSF before transplantation. Abnormal CSF (CSF+) was detected via conventional cytology and MFC in 44 patients at any time after diagnosis. A control group of 175 CSF-normal (CSF-) patients was generated via propensity score matching (PSM) analyses according to sex, age at transplant, and white blood cell count at diagnosis. RESULTS: Compared to those in the CSF-negative group, the conventional cytology positive and MFC+ groups had comparable 8-year nonrelapse mortality (NRM) (4%, 4%, and 6%, p = 0.82), higher cumulative incidence of relapse (CIR) (14%, 31%, and 32%, p = 0.007), lower leukemia-free survival (LFS) (79%, 63%, and 64%, p = 0.024), and overall survival (OS) (83%, 63%, and 68%, p = 0.021), with no significant differences between the conventional cytology positive and MFC+ groups. Furthermore, multivariate analysis confirmed that CSF involvement was an independent factor affecting OS and LFS. CONCLUSION: Our results indicate that pretransplant CSF abnormalities are adverse factors independently affecting OS and LFS after allotransplantation in AML patients.

Risk factors for positive post-transplantation measurable residual disease in patients with acute lymphoblastic leukemia.

BACKGROUND: The level of measurable residual disease (MRD) before and after transplantation is related to inferior transplant outcomes, and post-hematopoietic stem cell transplantation measurable residual disease (post-HSCT MRD) has higher prognostic value in determining risk than pre-hematopoietic stem cell transplantation measurable residual disease (pre-HSCT MRD). However, only a few work has been devoted to the risk factors for positive post-HSCT MRD in patients with acute lymphoblastic leukemia (ALL). This study evaluated the risk factors for post-HSCT MRD positivity in patients with ALL who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: A total of 1683 ALL patients from Peking University People's Hospital between January 2009 and December 2019 were enrolled to evaluate the cumulative incidence of post-HSCT MRD. Cox proportional hazard regression models were built for time-to-event outcomes. Multivariate analysis was performed to determine independent influencing factors from the univariate analysis. RESULTS: Both in total patients and in T-cell ALL or B-cell ALL, pediatric or adult, human leukocyte antigen-matched sibling donor transplantation or haploidentical SCT subgroups, positive pre-HSCT MRD was a risk factor for post-HSCT MRD positivity (P <0.001 for all). Disease status (complete remission 1 [CR1] vs. ≥CR2) was also a risk factor for post-HSCT MRD positivity in all patients and in the B cell-ALL, pediatric, or haploidentical SCT subgroups (P = 0.027; P = 0.003; P = 0.035; P = 0.003, respectively). A risk score for post-HSCT MRD positivity was developed using the variables pre-HSCT MRD and disease status. The cumulative incidence of post-HSCT MRD positivity was 12.3%, 25.1%, and 38.8% for subjects with scores of 0, 1, and 2-3, respectively (P <0.001). Multivariate analysis confirmed the association of the risk score with the cumulative incidence of post-HSCT MRD positivity and relapse as well as leukemia-free survival and overall survival. CONCLUSION: Our results indicated that positive pre-MRD and disease status were two independent risk factors for post-HSCT MRD positivity in patients with ALL who underwent allo-HSCT.

Single-cell immune landscape of measurable residual disease in acute myeloid leukemia.

Measurable residual disease (MRD) is a powerful prognostic factor of relapse in acute myeloid leukemia (AML). We applied the single-cell RNA sequencing to bone marrow (BM) samples from patients with (n=20) and without (n=12) MRD after allogeneic hematopoietic stem cell transplantation. A comprehensive immune landscape with 184,231 cells was created. Compared with CD8+ T cells enriched in the MRD-negative group (MRD-_CD8), those enriched in the MRD-positive group (MRD+_CD8) showed lower expression levels of cytotoxicity-related genes. Three monocyte clusters (i.e., MRD+_M) and three B-cell clusters (i.e., MRD+_B) were enriched in the MRD-positive group. Conversion from an MRD-positive state to an MRD-negative state was accompanied by an increase in MRD-_CD8 clusters and vice versa. MRD-enriched cell clusters employed the macrophage migration inhibitory factor pathway to regulate MRD-_CD8 clusters. These findings revealed the characteristics of the immune cell landscape in MRD positivity, which will allow for a better understanding of the immune mechanisms for MRD conversion.

[Analysis of Clinical Characteristics and Therapeutic Efficacy of Patients with Adult Acute Lymphoblastic Leukemia].

OBJECTIVE: To explore the clinical characteristics and therapeutic efficacy of patient with adult acute lymphoblastic leukemia(ALL). METHODS: Seventy-seven ALL patients diagnosed in the first affiliated hospital of Zhengzhou University from 2018 to 2019 were selected. The immunotyping, fusion gene and gene mutation were detected by flow cytometry, real-time quantitative polymerase chain reaction (RT-PCR) and next generation sequencing (NGS). RESULTS: Among 77 patients with ALL, 66 were B-ALL, 9 were T-ALL. CD7 and cCD3 were the most valuable for the diagnosis of T-ALL, CD19 and cCD79a were the most valuable for the diagnosis of B-ALL, and CD58, CD123 were highly expressed in B-ALL. Three fusion genes: BCR-ABL (20.8%), MLL-AF4 (5.19%) and E2A-PBX1 (2.60%) were detected by RT-PCR and 10 mutant genes were detected by NGS (the total detection rate was 33.47%). The highest mutation rates were IL-7R (6 cases), NOTCH1 (6 cases), TP53 (5 cases) and FLT-3 (4 cases). Patients with IL-7R, NOTCH1 and TP53 mutations showed poor response to induction chemotherapy. CONCLUSION: The CD123, IL-7R, NOTCH1 and TP53 may be risk factors for prognosis, however, the increase of case number and prolonging of follow-up time are needed to further confirm.

[Mutation and Clinical Feature of IL-7R in Adult Patients with Acute Lymphoblastic Leukemia].

OBJECTIVE: To investigate the IL-7R gene mutation and clinical features of adult patients with acute lymphoblastic leukemia (ALL). METHODS: One hundred sixty-four cases of newly treated adults with ALL from May 2016 to December 2018 were selected. Targeted and specific next-generation sequencing technology was used to detected a total of 16 types of Ph-like ALL mutations, which include IL-7R mutation, and the cilinical features, rate, types and sites of IL-7R were analyzed. RESULTS: IL-7R mutation was determined in 10 cases of 164 adult patients with ALL and the total mutation frequency was 13 times (6.1%). Out of 10 cases 5 cases were male (50%), 5 cases were female (50%). 6 cases of B-ALL ( 60% ) and 4 cases of T-ALL (40%). The mutation site of all cases was located at exon 6, among which 6 cases had replacement mutations, 3 cases had deletion mutations and 4 cases had insertion mutations. In addition, 1 triple and 1 double mutation of IL-7R were found. Besides, six mutation sites were newly identified, including: c.720_724del, c.723_726del, c.721_722insAGTG, c.727_728insTAACGGCCCCCTGCT, c.727_728insATGCAGGGAGCGAA and c.728_729insAAGTGTCA. CONCLUSION: Six novel mutation sites and a poor manifestation of IL-7R have been explored in this research. Thus more samples are required to study the effects of IL-7R mutation on ALL treatment.