A Real-world Perspective of CD123 Expression in Acute Leukemia as Promising Biomarker to Predict Treatment Outcome in B-ALL and AML

IntroductionCD123 is overexpressed in many hematologic malignancies and found to be useful in characterizing leukemic blasts of both acute myeloid leukemia (AML) and B-acute lymphoblastic leukemia (B-ALL). CD123 has been recently found to be a marker of leukemic stem cells, and its utility to measure residual disease and potential role in disease relapse is under evaluation.Materials and MethodsHerein, we have evaluated the expression of CD123 in 757 samples of acute leukemia including 479 treatment-naive and 278 follow-up samples and compared with post-induction morphologic complete remission and measurable residual disease (MRD) status. Multiparametric flow cytometry was used for assessment of CD123 expression and immunophenotypic characterization of leukemic blasts at diagnostic and MRD assessment time points.ResultsUsing variable cutoffs of 5%, 10%, and 20% to define a case as CD123-positive, expression of CD123 was observed in 75.6%, 66.2%, and 50% of AML and 88.6%, 81.8%, and 75% of B-ALL, respectively. Of 11 patients, 7 (63.63%) had mixed phenotype acute leukemia, but none of the 12 patients with T-acute lymphoblastic leukemia showed positivity for CD123. CD123 expression at diagnosis was associated with post-induction MRD-positive status in both B-ALL (P < .001) and AML (P = .001). We also evaluated the utility of CD123 as a leukemia-associated aberrant immunophenotype and found it to be useful in both patients with AML (baseline, 50.6%; follow-up, 53%) and B-ALL (baseline, 75%; follow-up, 73.07%).ConclusionsIn conclusion, CD123 may be considered as a cardinal marker for residual disease assessment and response evaluation in AML and B-ALL.     

Enrichment of N-Cadherin and Tie2-bearing CD34/CD38/CD123 leukemic stem cells by chemotherapy-resistance

Acute myeloid leukemia (AML) arises from genetic changes at the level of stem cell, various mutations have been elucidated, including AML1–ETO fusion gene has been shown as the representative target of cellular transformation for LSCs originating from hematopoietic stem cells (HSCs) compartment. LSCs resemble HSCs with respect to self-renewal capacity and chemotherapy-resistance. However, LSCs possess specific cell-surface markers, they are proposed to reside within the CD34⁺/CD38⁻/CD123⁺ compartment. And the interaction mediated by adhesion molecules between LSCs and niche played a role in chemoresistance of LSCs. Therefore, study on the LSCs surface makers related to niche is helpful for the potential target therapy in the future. In this study, the proportions of CD34⁺/CD38⁻/CD123⁺ LSCs compartment co-expressing the three adhesion molecules, N-Cadherin, Tie2 and CD44, respectively, from AML patients before and after chemotherapy were analyzed. We demonstrated N-Cadherin and Tie2 positive CD34⁺/CD38⁻/CD123⁺ LSCs populations could be enriched by chemotherapy. Furthermore, AML1/ETO fusion signals and MDR1 expression were detected on the CD34⁺/CD38⁻/CD123⁺ LSCs populations expressing N-Cadherin and Tie2. Therefore, N-Cadherin and Tie2 are probably the potential markers for identification of LSCs.     

Leukemic Stem Cell (CD34+/CD38–/TIM3+) Frequency in Patients with Acute Myeloid Leukemia: Clinical Implications

This study aimed to address the prognostic relevance of CD34⁺/CD38^–/TIM3⁺ leukemic stem cell (LSC) frequency in patients with acute myeloid leukemia (AML) and its impact on patient outcome. We analyzed the expression of LSC markers (CD34⁺/CD38^–/TIM3⁺) using flow cytometry in bone marrow samples of 53 AML cases before and after induction chemotherapy. The LSC frequency at diagnosis was significantly higher compared with that postinduction (P < .001). Patients were categorized into high LSC expressers (≥ median) and low expressers (< median). Patients with AML with high number of LSCs at diagnosis had significantly lower induction of remission response (P = .0104), shorter disease-free survival, and shorter overall survival (P < .001 for both) compared with those with lower LSC count. Cox regression analysis revealed that LSC frequency at diagnosis is an independent prognostic factor in AML. Assessment of LSCs (CD34⁺/CD38^–/TIM3⁺) at diagnosis is recommended for refining of AML risk stratification.     

Outcome of CD20-positive Adult B-cell Acute Lymphoblastic Leukemia and the Impact of Rituximab Therapy

BackgroundIn adult B cell precursor acute lymphoblastic leukemia (BCP-ALL), CD20 expression has generally been associated with an adverse prognosis. Incorporating rituximab to standard of care is found to improve the outcome of CD20⁺ BCP-ALL. The aim of this study is to estimate the prognostic effect of CD20 expression and the impact of rituximab in BCP-ALL in Saudi Arabia.Patients and MethodsWe performed a retrospective study of 55 Saudi adult patients with BCP-ALL in King Fahad Specialist Hospital in Dammam from 2008 to 2017.ResultsThe proportion of CD20⁺ cases was approximately 55%. Excluding rituximab-treated patients, the 5-year overall survival (OS) rate of CD20⁺ patients was lower than CD20⁻ patients (56% vs. 66%; P = .62). Among CD20⁺ patients, the proportion that received rituximab was approximately 27%. Comparing CD20⁺ patients with and without rituximab, all patients who received rituximab achieved complete remission (CR) 4 weeks post-induction. The 3-year OS rate (88% vs. 63%; P = .35) and the 2-year event-free survival rate (70% vs. 68%; P = .75) were in favor of rituximab. In univariate and multivariate analyses, CR 4 weeks post-induction is recognized as an independent predictor of outcome. However, differences in survival rates did not have a statistical significance.ConclusionCD20 expression in adult patients with BCP-ALL seems to be higher in Saudi Arabians than in Caucasians, and it seems to have a tendency towards an inferior outcome in terms of OS. Incorporating rituximab to standard of care seems to improve the outcome in terms of CR, OS, and event-free survival.     

Measurable Residual Disease Assessment and Allogeneic Transplantation as Consolidation Therapy in Adult Acute Lymphoblastic Leukemia in Colombia

IntroductionDetectable minimal residual disease (MRD) after therapy for acute lymphoblastic leukemia (ALL) is the strongest predictor of hematologic relapse. The objective of the study was to assess disease-free survival (DFS) and overall survival (OS) of patients with ALL according with MRD status at the end of induction therapy in a Colombian population.Patients and MethodsWe assessed a retrospective cohort to compare DFS and OS in adults with de novo ALL according to MRD status at the end of induction chemotherapy, and the type of postinduction consolidation strategy used.ResultsA total of 165 adults with ALL were included in the MRD part of the study, 73 patients in the MRD-negative group and 92 in the MRD-positive group. Median DFS for the MRD-positive group was 11 months (95% confidence interval, 11.7-22.2) and was not reached for the MRD-negative group (P < .001). At 3 years, DFS was 18% and 55%, respectively (P < .001). The median OS for MRD-positive patients was 16 months (95% confidence interval, 8.8-23.15) and was not reached in the MRD-negative group. At 3 years, OS was 26% and 51% for the former and latter group, respectively. Among subjects who did not receive a transplant, median DFS was 21 months for MRD-negative patients and 9 months for MRD-positive patients (P < .001). The median DFS was not reached in either group, whereas 3-year DFS was 64% for MRD-negative and 70% for MRD-positive patients who underwent transplantation in first remission (P = .861).ConclusionMRD status at the end of induction is an independent prognostic factor for DFS and OS in adult ALL. Allogeneic transplantation in first remission could overcome the adverse prognostic impact of MRD.     

N-Cadherin and Tie2 positive CD34CD38CD123 leukemic stem cell populations can develop acute myeloid leukemia more effectively in NOD/SCID mice

Emerging studies suggest that the population of malignant cells found in human acute myelogenous leukemia (AML) arises from a rare population of leukemic stem cells (LSCs). A lot of investigators have reported the identification of cell surface markers, such as CD123. Here, we report the identification of N-cadherin and Tie2 as LSCs markers. Inoculation of CD34⁺CD38⁻CD123⁺N-cadherin⁺ and CD34⁺CD38⁻CD123⁺ Tie2⁺ population can induce leukemia in NOD/SCID mice. The leukemic blast cells from the primary leukemic mice could also induce leukemia in the secondary transplantation. These findings suggested that N-cadherin and Tie2 were the important markers that can assist in leukemia development.     

CD34+/CD38− acute myelogenous leukemia cells aberrantly express CD82 which regulates adhesion and survival of leukemia stem cells

To identify molecular targets in leukemia stem cells (LSCs), this study compared the protein expression profile of freshly isolated CD34⁺/CD38^? cells with that of CD34⁺/CD38⁺ counterparts from individuals with acute myelogenous leukemia (n = 2, AML) using isobaric tags for relative and absolute quantitation (iTRAQ). A total of 98 proteins were overexpressed, while six proteins were underexpressed in CD34⁺/CD38^? AML cells compared with their CD34⁺/CD38⁺ counterparts. Proteins overexpressed in CD34⁺/CD38^? AML cells included a number of proteins involved in DNA repair, cell cycle arrest, gland differentiation, antiapoptosis, adhesion, and drug resistance. Aberrant expression of CD82, a family of adhesion molecules, in CD34⁺/CD38^? AML cells was noted in additional clinical samples (n = 12) by flow cytometry. Importantly, down‐regulation of CD82 in CD34⁺/CD38^? AML cells by a short hairpin RNA (shRNA) inhibited adhesion to fibronectin via up‐regulation of matrix metalloproteinases 9 (MMP9) and colony forming ability of these cells as assessed by transwell assay, real‐time RT‐PCR, and colony forming assay, respectively. Moreover, we found that down‐regulation of CD82 in CD34⁺/CD38^? AML cells by an shRNA significantly impaired engraftment of these cells in severely immunocompromised mice. Taken together, aberrant expression of CD82 might play a role in adhesion of LSCs to bone marrow microenvironment and survival of LSCs. CD82 could be an attractive molecular target to eradicate LSCs.     

Hematopoietic Cell Transplantation for Mantle Cell Lymphoma: Predictive Value of Pretransplant Positron Emission Tomography/Computed Tomography and Bone Marrow Evaluations for Outcomes

BackgroundThe prognostic roles of 18F-fludeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging and marrow involvement evaluation on outcomes following autologous and allogeneic hematopoietic cell transplantation (HCT) for mantle cell lymphoma (MCL) are uncertain and require more data.Patients and MethodsWe categorized 66 patients with MCL who received HCT (38 autologous and 28 allogeneic) on the basis of pre-HCT residual disease (RD) status as assessed by marrow MCL morphology and flow/molecular analysis and PET/CT imaging to RD positive (RD⁺) (either or both measures positive) and RD⁻ (both negative). We analyzed the predictive value of these RD detection methods on transplant outcomes.ResultsThe 2-year relapse rate after autograft was significantly higher in pre-HCT RD⁺ patients (46% [95% CI 16-77%]) than in patients who were RD⁻ (19% [95% CI 0-42%]; P = .02), leading to worse 5-year disease-free survival (DFS) in RD⁺ patients (46% [95% CI 14%-73%] vs. 68% [95% CI 33-87%], P = .04). In multivariate analysis, RD⁺ status was associated with a reduction in DFS (hazard ratio, 5.6; P = .02). Most allogeneic HCT recipients had advanced disease and most were RD⁺ (12 PET/CT⁺; 5 marrow-positive). The 5-year DFS and relapse rates after allogeneic HCT were 34% and 25% for all patients and 40% and 33% for RD⁺ recipients, suggesting that active disease at the time of allograft does not preclude long-term remissions in advanced MCL.ConclusionBoth autologous and allogeneic HCT lead to promising long-term survival. RD detected prior to autograft was associated with increased relapse and worse 5 year DFS. Allograft recipients had favorable long-term outcomes even in presence of pre-HCT detectable disease.     

Neuroendocrine Differentiation,Microsatellite Instability,and Tumor-infiltrating Lymphocytes in Advanced Colorectal Cancer With BRAF Mutation

BackgroundApproximately 10% of metastatic colorectal cancer (mCRC) cases will harbor the BRAF p.V600E mutation (BRAF-mCRC) and have been associated with a poor prognosis. Although they are usually considered a unique clinical entity, biologic heterogeneity has been described. We performed an extensive clinicopathologic study of a multicenter series of BRAF-mCRC to highlight differences between tumors with microsatellite instability (MSI) and microsatellite stable tumors, focusing on both inflammatory profiles and neuroendocrine differentiation.MethodsWe included 59 BRAF-mCRC cases and collected the clinical data (ie, surgery, treatment, and follow-up). We evaluated MSI status, budding, lympho-angioinvasion, neuroinvasion, extent of active stroma, CD3⁺ and CD8⁺ intratumoral and peritumoral lymphocytes, programmed cell death ligand 1, p53, Ki-67, synaptophysin, and CDX2 expression.ResultsThe 22 MSI BRAF-mCRC cases were associated with the right side (P < .0001), an expansive grown pattern (P < .01), programmed cell death ligand 1 expression (P < .0001), high CD8 T-cell content (P = .0001), and lymph node metastases (P < .029). The 37 MSS BRAF-mCRC cases were characterized by a greater stromal component (P = .0002), pulmonary metastases (P = .095), and p53 and synaptophysin immunoreactivity (P = .004 and P = .001, respectively). Univariate analysis demonstrated that MSI and a high CD8 T-cell content were associated with a 34% (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.34-1.28; P = .2) and 33% (HR, 0.67; 95% CI, 0.45-0.99; P = .04) reduction in the risk of death, respectively. The combined presence of MSI and CD8 T-cell content decreased the hazard of mortality ≤ 63% (HR, 0.37; 95% CI, 0.14-0.97; P = .2), which was slightly reduced after multivariate analysis.ConclusionA simultaneous evaluation of MSI, CD8 T-cell content, and neuroendocrine markers could allow for the identification of subsets of BRAF-mCRC with a different prognosis and potential eligibility for specific treatments.     

Minimal Residual Disease and Survival Outcomes in Patients With Chronic Lymphocytic Leukemia: A Systematic Review and Meta-analysis

BackgroundPatients with chronic lymphocytic leukemia (CLL) who achieve undetectable minimal residual disease (U-MRD) (ie, < 10^-4 detectable leukemic cells in peripheral blood or bone marrow) have better outcomes than those with detectable MRD. To assess the magnitude of improvement of progression-free survival (PFS) or overall survival (OS) in patients who achieved U-MRD after upfront chemotherapy (CT) or chemo-immunotherapy (CIT), we conducted a systematic review and meta-analysis.Materials and MethodsThe screening process adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines. The search strategy yielded 365 records, including 22 articles assessed for eligibility.ResultsEleven studies comprising 2457 patients with CLL treated in upfront with CT or CIT were considered suitable for inclusion in the quantitative meta-analysis. Nine studies (n = 2088) provided data on the impact of MRD on PFS and 6 (n = 1234) on OS. MRD was the main endpoint in only 2 of these studies (n = 213). Tests of heterogeneity revealed significant differences among studies for PFS and OS, which highlights differences across studies. U-MRD status was associated with significantly better PFS overall (P < .001) and in patients who achieved conventional complete remission (P = .01). Regarding OS, U-MRD predicted longer OS globally (P < .001) but not in patients having achieved complete remission (P = .82).ConclusionsU-MRD status after treatment with CT or CIT in newly diagnosed CLL is associated with long-term survival. These findings provide quantitative evidence to support the integration of MRD assessment as an end point in clinical trials of CLL.     

Comparison of Three Doses of Cytarabine Consolidation for Intermediate- and Adverse-risk Acute Myeloid Leukemia: Real World Evidence From Thai Acute Myeloid Leukemia Registry

BackgroundIntermediate or high doses of cytarabine (IDAC or HiDAC) were recommended as postremission chemotherapy for acute myeloid leukemia (AML). This retrospective study investigated the real-world outcomes of 3-different cytarabine doses from the multicenter Thai AML registry database.Patients and MethodsThe intermediate- and adverse-risk AML patients (N = 258) who achieved complete remission and proceeded to single-agent cytarabine consolidation were enrolled.ResultsThe median relapse-free survival (RFS) using IDAC 1.5 g/m², high-dose cytarabine (HiDAC) 2 g/m², and HiDAC 3 g/m² were 12.6, 11.7, and 13 months, respectively. The median overall survival (OS) using IDAC 1.5 g/m², HiDAC 2 g/m², and HiDAC 3 g/m² were 34.9, 22.7, and 23.7 months, respectively. No significant difference in RFS and OS was detected between the 3 doses. Secondary AML, white blood cell > 100×10⁹/L and the adverse-risk AML were independent prognostic factors for inferior survival (P= .008, P < .001, P= .014). Patients who completed 3 to 4 cycles of consolidation had significantly superior RFS and OS (P< .001, P< .001). Febrile neutropenia occurred in 72.9% of IDAC, 73.8% of HiDAC 2 g/m², and 78.1% of HiDAC 3 g/m² without statistical significance. However, the incidence of septic shock was significantly higher after HiDAC 3 g/m² compared to IDAC regimen (8% vs. 3%, P= .037).ConclusionIDAC is an appropriate regimen for postremission chemotherapy for intermediate- and adverse-risk AML. The higher dosing levels may not produce any benefits to patients and may increase incidence of septic shock. The number of consolidation cycles may impact on survivals rather than the intensity of cytarabine.     

Clinical Characteristics and Outcomes of Single Versus Double Hormone Receptor–Positive Breast Cancer in 2 Large Databases

PurposeTo identify biologic and outcome differences between double hormone receptor (HR)-positive (dHR⁺, estrogen receptor (ER)⁺/progesterone receptor [PgR⁺]) and single HR-positive (sHR⁺, either ER⁺/PgR⁻ or ER⁻/PgR⁺) breast cancer; and to explore whether hormone therapy (HT) response in HER2-negative breast cancer correlates with HR status.Patients and MethodsThis retrospective study was conducted by using 2 large breast cancer databases: the Surveillance, Epidemiology, and End Results (SEER) database and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) clinical data set. Cox regression analysis was used to estimate overall survival (OS) and breast cancer–specific survival (BCSS) among sHR⁺ and dHR⁺ patients.ResultsIn the SEER database, dHR⁺ patients had significantly longer OS and BCSS than ER⁺/PgR⁻ patients in short-term follow-up (OS: hazard ratio = 0.620; 95% confidence interval [CI], 0.590, 0.652; P < .001; BCSS: hazard ratio = 0.493; 95% CI, 0.462, 0.526; P < .001). Meanwhile, ER⁻/PgR⁺ patients had younger age, larger tumor size, and higher disease grade than dHR⁺ and ER⁺/PgR⁻ patients. In patients who received HT, dHR⁺ patients had a more favorable OS than ER⁺/PgR⁻ patients (hazard ratio = 0.789; 95% CI, 0.635, 0.982; P = .034), and ER⁻/PgR⁺ patients had a worse OS than ER⁺/PgR⁻ patients at 10 years’ follow-up (hazard ratio = 7.991; 95% CI, 1.053, 60.644; P = .044). However, these groups had similar outcomes over longer periods.ConclusionIn HER2-negative breast cancer, sHR⁺ patients are associated with relatively worse characteristics and worse short-term outcomes than dHR⁺ patients. Additionally, the outcome of patients receiving HT may differ according to the HR status. However, further studies are needed to confirm these conclusions.     

Predictors of CD34+ Cell Mobilization and Collection in Adult Men With Germ Cell Tumors: Implications for the Salvage Treatment Strategy

BackgroundHigh-dose chemotherapy with tandem or triple carboplatin and etoposide course is currently the first curative choice for relapsing GCT. The collection of an adequate amount of hematopoietic (CD34⁺) stem cells is a priority.Patients and MethodsWe analyzed data of patients who underwent HDCT at 2 referral institutions. Chemotherapy followed by myeloid growth factors was applied in all cases. Uni- and multivariable models were used to evaluate the association between 2 prespecified variables and mobilization parameters. Analyses included only the first mobilizing course of chemotherapy and mobilization failures.ResultsA total of 116 consecutive patients underwent a mobilization attempt from December 1995 to November 2012. Mobilizing regimens included cyclophosphamide (CTX) 7 gr/m² (n = 39), cisplatin, etoposide, and ifosfamide (PEI) (n = 42), paclitaxel, cisplatin, and gemcitabine (TPG) (n = 11), and mixed regimens (n = 24). Thirty-seven percent were treated in first-line, 50% (n = 58) in second-line, 9.5% (n = 11) and 3.4% (n = 4) in third- and fourth-line settings, respectively. Six patients did not undergo HDCT because they were poor mobilizers, 2 in first- and second-line (1.9%), and 4 beyond the second-line (26.7%). In the multivariable model, third-line or later setting was associated with a lower CD34⁺ cell peak/μL (P = .028) and a lower total CD34⁺/kg collected (P = .008). The latter was also influenced by the type of mobilizing regimen (P < .001).ConclusionA decline in significant mobilization parameters was found, primarily depending on the pretreatment load. Results lend support to the role of CD34⁺ cell mobilization in the therapeutic algorithm of relapsing GCT, for whom multiple HDCT courses are still an option, and potentially a cure.     

Residual Cancer Lymphocytes in Patients With Chronic Lymphocytic Leukemia After Therapy Show Increased Expression of Surface Antigen CD52 Detected Using Quantitative Fluorescence Cytometry

BackgroundRituximab and alemtuzumab, mAbs used in recent years to treat CLL, are directed against antigens CD20 and CD52. CD20 is not highly expressed by CLL tumor cells, and rituximab does not have significant effectiveness in CLL unless combined with chemotherapy. Alemtuzumab targets CD52, which is much more highly expressed, and is currently the most effective agent used alone for CLL. Variability in expression of both antigens among these patients might be related to different individual therapeutic responses to mAb therapy.Patients and MethodsA total 95 patients diagnosed with CLL and/or SLL were divided into 4 groups: (1) untreated; (2) in complete or partial remission; (3) disease in progression; and (4) diagnosed with SLL. Flow cytometry of peripheral blood cells included gating of the CD5⁺CD19⁺ tumor population, within which mean fluorescence intensity of fluorescein isothiocyanate (FITC) conjugated with anti-CD20 or anti-CD52 antibody was measured. The resulting expression of the 2 antigens was deduced from the calibration curve using Quantum FITC particles.ResultsExpression of CD20 showed no significant differences among the 4 groups of patients. However, significantly greater expression of surface antigen CD52 was recorded in patient group 2 in complete or partial remission (P < .001).ConclusionThe residual population of CLL cells after therapy is characterized by increased surface detection of CD52. Although the exact cause of this phenomenon is unknown, our results provide a basis to consider the potential for CLL consolidation therapy using alemtuzumab.     

Co-expression of stem cell genes CD133 and CD44 in colorectal cancers with early liver metastasis

PurposeTo investigate the expression status and clinical implications of stem cell genes CD133 and CD44 in the colorectal cancers with early liver metastasis.Materials and methodsThe differential genes of early liver metastases in colorectal cancer were detected by RT² Profiler? PCR Array. The expression and the relationship of stem cell gene CD133 and CD44 were analyzed by immunofluorescent tests.ResultsCD133 and CD44 were significantly higher co-expressed in colorectal cancer with early liver metastases compared to those without early liver metastases, and the content of CD133 and CD44 proteins decreased following growth of the transplanted tumors. Of the 80 cases without early liver metastases, 12 were observed CD133 and CD44 proteins co-expression, while 36 of the 40 cases with early liver metastases were found CD133 and CD44 proteins co-expression (15% vs. 90%, P < 0.05). Survival analysis revealed CD133 and CD44 proteins co-expression was associated with poorest prognosis (57.14% vs. 87.41%, X² = 48.49, P = 0.001). After Cox regression, age, Duck’s stage, lymph node metastasis, and CD133 and CD44 proteins co-expression were shown to be the independent prognostic factors of colorectal cancers.ConclusionsCD133 and CD44 proteins were highly co-expressed in colorectal cancer with early liver metastases, and may be a potential biomarker for the early liver metastases.     

The Effect of Peritransplant Minimal Residual Disease in Adults With Acute Lymphoblastic Leukemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

BackgroundAllogeneic HSCT is highly effective for treating ALL. However, many ALL patients relapse after HSCT. There has been a continuing effort to improve identification of patients at high risk of relapse, with the goal of early intervention to improve outcome.Patients and MethodsIn this retrospective analysis, we examined the effect of MRD on the risk of hematologic relapse in 149 adult patients with ALL in morphologic remission undergoing allogeneic HSCT. MRD was assessed at the time of HSCT and after HSCT.ResultsPatients with pretransplant MRD had a trend for shorter progression-free survival (PFS) at 2 years compared with patients without MRD, nearing statistical significance; 28% versus 47%, P = .08, on univariate analysis. This trend remained on multivariate analysis with better PFS in patients without MRD at the time of HSCT, hazard ratio (HR), 0.62 (95% confidence interval, 0.37-1.04); P = .07. Additionally, emergence of MRD after HSCT was a strong predictor for overt hematologic relapse (HR, 4; P < .001) with a median latency interval of 3.8 months.ConclusionThese findings demonstrate the predictive value of monitoring for MRD around the time of transplant in adult patients with ALL.     

Prognostic factors in normal karyotype acute myeloid leukemia in the absence of the FLT3-ITD mutation

Patients with normal karyotype acute myeloid leukemia (NK-AML) without the FLT3 internal tandem duplication (FLT3-ITD) mutation account for approximately 30% of all AML cases, and exhibit a heterogeneous clinical outcome. Except for NPM1 mutations, prognostic factors in this subgroup of AML are still unclear. Here we explored the impact of immunophenotypic markers along with NPM1 mutations and clinical features on the outcome of 133 FLT3-ITD negative NK-AML patients. CD34 expression was associated with poorer complete remission (CR) rate, disease-free survival (DFS), event-free survival (EFS), and overall survival (OS), whereas CD56 expression adversely affected EFS and OS. In contrast, NPM1 mutations correlated with an improved CR rate, DFS, and EFS. Moreover, males experienced shorter DFS and EFS, while older patients (≥60 years) had shorter EFS. Multivariate analysis of age, gender, NPM1, CD34, and CD56 showed NPM1 mutation was an independent predictor of better CR rate, DFS, and EFS (P < 0.001, P = 0.003, and P = 0.006, respectively). In addition, older age was associated with shorter DFS and EFS (P = 0.045 and P = 0.028, respectively), and CD56 positivity predicted shorter EFS (P = 0.012). Our results confirm the favorable impact of NPM1 mutations and identify the adverse prognostic relevance of CD56 expression in this subgroup of AML.