Along with PaO2/FiO2 ratio and lymphopenia, low HLA-DR monocytes are the only additional parameter that independently predicts the clinical course of undifferentiated SARS-CoV-2 patients in Emergency Departments.

Since 1/3 of patients deteriorate after their admission to the emergency department (ED), assessing the prognosis of COVID-19 patients is of great importance. But to date, only lymphopenia and PaO2/FiO2 (P/F) ratio have been reported as partly predictive of COVID-19 further deterioration and their association has not been evaluated. We asked whether other key biomarkers of SARS-CoV2 immunologic defects - increase in circulating immature granulocytes (IGs), loss of monocyte HLA-DR (mHLA-DR) expression and monocyte differentiation blockade - could also predict further COVID-19 deterioration. A series of 284 consecutive COVID-19 patients with, as sole inclusion criterion of being an adult, were prospectively enrolled at ED admission (D0) of two different hospitals: one for the exploratory (180 patients) and one for the confirmatory cohort (104 patients). Deterioration was assessed over the next seven days. Neither increased IG levels nor monocyte differentiation blockade predicted patient worsening. Among more than 30 clinical, biological and radiological parameters, the value of decreased PaO2/FiO2 (P/F) ratio and lymphopenia for prediction of further COVID-19 deterioration was strongly confirmed and the loss of mHLA-DR was the only additional independent marker. Combined together in a simple OxyLymphoMono score, the three variables perfectly predicted patients who did not worsen and correctly predicted worsening in 59% of cases.By highlighting lymphocyte and monocyte defects as preceding COVID-19 deterioration, these results point on early immunosuppression in COVID-19 deterioration. Combining P/F ratio, lymphopenia and loss of mHLA-DR together in a simple and robust score could offer a pragmatic method for COVID-19 patient stratification.

Machine learning identifies the independent role of dysplasia in the prediction of response to chemotherapy in AML.

The independent prognostic impact of specific dysplastic features in acute myeloid leukemia (AML) remains controversial and may vary between genomic subtypes. We apply a machine learning framework to dissect the relative contribution of centrally reviewed dysplastic features and oncogenetics in 190 patients with de novo AML treated in ALFA clinical trials. One hundred and thirty-five (71%) patients achieved complete response after the first induction course (CR). Dysgranulopoiesis, dyserythropoiesis and dysmegakaryopoiesis were assessable in 84%, 83% and 63% patients, respectively. Multi-lineage dysplasia was present in 27% of assessable patients. Micromegakaryocytes (q = 0.01), hypolobulated megakaryocytes (q = 0.08) and hyposegmented granulocytes (q = 0.08) were associated with higher ELN-2017 risk. Using a supervised learning algorithm, the relative importance of morphological variables (34%) for the prediction of CR was higher than demographic (5%), clinical (2%), cytogenetic (25%), molecular (29%), and treatment (5%) variables. Though dysplasias had limited predictive impact on survival, a multivariate logistic regression identified the presence of hypolobulated megakaryocytes (p = 0.014) and micromegakaryocytes (p = 0.035) as predicting lower CR rates, independently of monosomy 7 (p = 0.013), TP53 (p = 0.004), and NPM1 mutations (p = 0.025). Assessment of these specific dysmegakarypoiesis traits, for which we identify a transcriptomic signature, may thus guide treatment allocation in AML.

Flow cytometry detection of CD138 expression continuum between monotypic B and plasma cells is associated with both high IgM peak levels and MYD88 mutation and contributes to diagnosis of Waldenström macroglobulinemia.

BACKGROUND: Differential diagnosis of Waldenström macroglobulinemia (WM) with other indolent B-cell malignancies is still a challenge. Here, we propose an original and simple analysis of routine flow cytometry (FCM) unraveling the characteristic ongoing plasma cell (PC) differentiation of WM tumor B-cells. METHODS: FCM analysis of both B-cells and PC was performed on a series of 77 patients with IgM peak. MYD88 and CXCR4 mutations were studied using an allele-specific PCR and by high throughput sequencing. RESULTS: Twenty seven (35%), 46 (58%) and 4 (5%) patients were classified as WM, IgM monoclonal gammopathy of undetermined significance (MGUS) or other B-NHL respectively. MYD88 mutation was found in 25/27 WM (93%) and in 29/46 MGUS (63%). Using FCM, monotypic B-cells were found in 27/27 WM (100%) and 34/46 MGUS (74%). Monotypic CD138pos/CD38pos PCs were detected in 23/27 WM (85%) and 25/46 MGUS (54%). Highlighting the ongoing PC differentiation of WM tumor B-cells by FCM, we evidenced a CD138 expression continuum between monotypic B-cells and PCs. This pattern remained absent in control samples and was significantly associated with higher IgM peaks (p = 6.10-5 ) and MYD88 mutations (p = 10-3 ) in both WM and MGUS cases. CONCLUSIONS: FCM exploration of both B-cells and PC led to identify a CD138 expression continuum as an objective marker of ongoing PC differentiation of WM tumor cells and was strongly associated with increased IgM peak levels and MYD88 mutations. This approach could contribute to place FCM at the forefront of WM diagnosis.

Mutational profile and benefit of gemtuzumab ozogamicin in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a highly heterogeneous disease both in terms of genetic background and response to chemotherapy. Although molecular aberrations are routinely used to stratify AML patients into prognostic subgroups when receiving standard chemotherapy, the predictive value of the genetic background and co-occurring mutations remains to be assessed when using newly approved antileukemic drugs. In the present study, we retrospectively addressed the question of the predictive value of molecular events on the benefit of the addition of gemtuzumab ozogamicin (GO) to standard front-line chemotherapy. Using the more recent European LeukemiaNet (ELN) 2017 risk classification, we confirmed that the benefit of GO was restricted to the favorable (hazard ratio [HR], 0.54, 95% confidence interval [CI], 0.30-0.98) and intermediate (HR, 0.57; 95% CI, 0.33-1.00) risk categories, whereas it did not influence the outcome of patients within the adverse risk subgroup (HR, 0.93; 95% CI, 0.61-1.43). Interestingly, the benefit of GO was significant for patients with activating signaling mutations (HR, 0.43; 95% CI, 0.28-0.65), which correlated with higher CD33 expression levels. These results suggest that molecular aberrations could be critical for future differentially tailored treatments based on integrated genetic profiles that are able to predict the benefit of GO on outcome.

How should we diagnose and treat blastic plasmacytoid dendritic cell neoplasm patients?

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive leukemia for which we developed a nationwide network to collect data from new cases diagnosed in France. In a retrospective, observational study of 86 patients (2000-2013), we described clinical and biological data focusing on morphologies and immunophenotype. We found expression of markers associated with plasmacytoid dendritic cell origin (HLA-DRhigh, CD303+, CD304+, and cTCL1+) plus CD4 and CD56 and frequent expression of isolated markers from the myeloid, B-, and T-lymphoid lineages, whereas specific markers (myeloperoxidase, CD14, cCD3, CD19, and cCD22) were not expressed. Fifty-one percent of cytogenetic abnormalities impact chromosomes 13, 12, 9, and 15. Myelemia was associated with an adverse prognosis. We categorized chemotherapeutic regimens into 5 groups: acute myeloid leukemia (AML)-like, acute lymphoid leukemia (ALL)-like, lymphoma (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP])-like, high-dose methotrexate with asparaginase (Aspa-MTX) chemotherapies, and not otherwise specified (NOS) treatments. Thirty patients received allogeneic hematopoietic cell transplantation (allo-HCT), and 4 patients received autologous hematopoietic cell transplantation. There was no difference in survival between patients receiving AML-like, ALL-like, or Aspa-MTX regimens; survival was longer in patients who received AML-like, ALL-like, or Aspa-MTX regimens than in those who received CHOP-like regimens or NOS. Eleven patients are in persistent complete remission after allo-HCT with a median survival of 49 months vs 8 for other patients. Our series confirms a high response rate with a lower toxicity profile with the Aspa-MTX regimen, offering the best chance of access to hematopoietic cell transplantation and a possible cure.

Adult Bone Marrow Three-Dimensional Phenotypic Landscape of B-Cell Differentiation.

BACKGROUND: The different B-cell subsets in human bone marrow result from a dynamic equilibrium between endogenous production, B-cell bone marrow reentry and terminal plasma cell differentiation. Our aim was to define and quantify the different medullary B-cell subsets. METHODS: A series of 32 normal adult bone marrows plus 15 normal adult blood samples was studied by nine color flow cytometry (CD10, CD19, CD24, CD27, CD34, CD38, CD45, IgM, and IgD). With the Kaluza software radar plots, two 2D triple parametric histograms (CD10/CD34/CD45 and CD27/IgM/IgD) were set-up to identify six progenitor and five mature B-cell subsets. RESULTS: Very early B-cell progenitors were CD19neg/CD10pos/CD34pos. B-cell progenitors were split into five subsets on the CD10/CD34/CD45 triple parametric histogram, sequentially ordered according to the loss of CD34 and CD10 and acquisition of surface IgM and IgD. CD19pos/CD38low mature B-cells were divided into four subsets on the CD27/IgM/IgD triple parametric histogram, with two stages of naïve B-cells and two CD27hi marginal zone and switched memory B-cell compartments. CD19pos/CD34neg/CD10low immature B-cells were the main bone marrow B-cell subset, accounting for one third of bone marrow B-cells. Transitional B-cells were the only immature bone marrow stage found in the blood. Compared to blood, the bone marrow was enriched in both marginal zone and switched B-cells. CONCLUSION: We provide the first analysis of 3D B-cell differentiation by multicolor flow cytometry leading to propose reference values for each bone marrow and blood B-cell compartment. This warrants further exploration of normal and pathological human B-cell maturation. © 2018 International Clinical Cytometry Society.

Immature Granulocytes: A Risk Factor of Infection after Cardiac Surgery.

BACKGROUND: Similarly, to sepsis, cardiac surgery with cardiopulmonary bypass (CPB) induces major changes in leukocyte subsets. Immature granulocytes (IGs) increase both in sepsis and after open-heart surgery. Secondary infections are a major complication of cardiac surgery with CPB. We hypothesized that the assessment of leukocyte subsets with multicolor flow cytometry (FCM) could help the front-line clinician to better identify patients at high risk of infectious complications in this clinical setting. METHODS: In this single-center observational pilot study, we identified 26 leukocyte subsets using three combinations of antibodies (from 5 to 10 colors per combinations): one devoted to granulocytes, one to lymphocyte subpopulations and one for rare cells (plasma cells and dendritic cells). Blood samples were obtained preoperatively and immediately after open-heart surgery under CPB in 59 patients without immuno-depression, chronic or neoplastic inflammatory disease, and immunosuppressive treatment. Secondary infections during hospital stay were recorded. RESULTS: Patients exhibited postoperative NK and T-cell lymphopenia, increased levels of IGs and monocytes with low levels of surface HLA DR. Twelve patients developed secondary infectious complications. Only immediate postoperative IG levels were significantly higher in these patient (6.6 [6; 7.39] G/L vs. 3.8 [2.67; 5.72] G/L, P = 0.01). Patients with immediate postoperative increase of IGs developed more frequently infectious complication (10/22 [46%] vs. 2/37 [5%]: P < 0.001). CONCLUSIONS: This study suggests that postoperative increase of IGs is related to postoperative organ failure and promises to help in early identification of patients at risk of infectious complications after open-heart surgery under CPB. © 2018 International Clinical Cytometry Society.

Multicentric Standardized Flow Cytometry Routine Assessment of Patients With Sepsis to Predict Clinical Worsening.

BACKGROUND: In this study, we primarily sought to assess the ability of flow cytometry to predict early clinical deterioration and overall survival in patients with sepsis admitted in the ED and ICU. METHODS: Patients admitted for community-acquired acute sepsis from 11 hospital centers were eligible. Early (day 7) and late (day 28) deaths were notified. Levels of CD64pos granulocytes, CD16pos monocytes, CD16dim immature granulocytes (IGs), and T and B lymphocytes were assessed by flow cytometry using an identical, cross-validated, robust, and simple consensus standardized protocol in each center. RESULTS: Among 1,062 patients screened, 781 patients with confirmed sepsis were studied (age, 67 ± 48 years; Simplified Acute Physiology Score II, 36 ± 17; Sequential Organ Failure Assessment, 5 ± 4). Patients were divided into three groups (sepsis, severe sepsis, and septic shock) on day 0 and on day 2. On day 0, patients with sepsis exhibited increased levels of CD64pos granulocytes, CD16pos monocytes, and IGs with T-cell lymphopenia. Clinical severity was associated with higher percentages of IGs and deeper T-cell lymphopenia. IG percentages tended to be higher in patients whose clinical status worsened on day 2 (35.1 ± 35.6 vs 43.5 ± 35.2, P = .07). Increased IG percentages were also related to occurrence of new organ failures on day 2. Increased IG percentages, especially when associated with T-cell lymphopenia, were independently associated with early (P < .01) and late (P < .01) death. CONCLUSIONS: Increased circulating IGs at the acute phase of sepsis are linked to clinical worsening, especially when associated with T-cell lymphopenia. Early flow cytometry could help clinicians to target patients at high risk of clinical deterioration. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01995448; URL: www.clinicaltrials.gov.

Prognostic value of multicenter flow cytometry harmonized assessment of minimal residual disease in acute myeloblastic leukemia.

The assessment of minimal residual disease (MRD) in acute myeloblastic leukemia is of growing interest as a prognostic marker of patients' outcome. Multiparameter flow cytometry (MFC), tracking leukemia-associated immunophenotypic patterns, has been shown in several studies to be a useful tool to investigate MRD. Here, we report a multicenter prospective study which allowed to define a harmonized analysis strategy, as well as the efficacy of MFC MRD to predict outcome. This study included 276 patients, in 10 different MFC centers, of whom 268 had at least 1 MRD check point. The combination of a CD45, CD34, and CD33 backbone, with the addition of CD117, CD13, CD7, and CD15 in 2 five-color tubes allowed to define each patient's multiparameter immunophenotypic characteristics at diagnosis, according to a Boolean combination of gates. The same individual diagnosis gating strategy was then applied at each MRD time point for each patient. MRD levels were stratified according to log by log thresholds, from 5 × 10-2 (the classical morphological threshold to define remission) down to <5 × 10-5 . MRD was found to be constantly negative (<5 × 10-5 ) for 148 patients. Survival analyses significantly associated MRD negativity with a good prognosis and any positive value with poorer outcome. All P values were <0.0001 both for disease-free and overall survival at the earliest time point (post-induction, MRD1) as well as when considering all time points together. Finally, MRD levels were independent of cytogenetics and allowed in fact to further stratify all cytogenetics risk groups. In summary, this multicenter study demonstrates that a simple combination of immunophenotypic markers successfully allows for the detection of MRD in acute myeloblastic leukemia patients, with a strong correlation to outcome.

Immunophenotypic analysis of erythroid dysplasia in myelodysplastic syndromes. A report from the IMDSFlow working group.

Current recommendations for diagnosing myelodysplastic syndromes endorse flow cytometry as an informative tool. Most flow cytometry protocols focus on the analysis of progenitor cells and the evaluation of the maturing myelomonocytic lineage. However, one of the most frequently observed features of myelodysplastic syndromes is anemia, which may be associated with dyserythropoiesis. Therefore, analysis of changes in flow cytometry features of nucleated erythroid cells may complement current flow cytometry tools. The multicenter study within the IMDSFlow Working Group, reported herein, focused on defining flow cytometry parameters that enable discrimination of dyserythropoiesis associated with myelodysplastic syndromes from non-clonal cytopenias. Data from a learning cohort were compared between myelodysplasia and controls, and results were validated in a separate cohort. The learning cohort comprised 245 myelodysplasia cases, 290 pathological, and 142 normal controls; the validation cohort comprised 129 myelodysplasia cases, 153 pathological, and 49 normal controls. Multivariate logistic regression analysis performed in the learning cohort revealed that analysis of expression of CD36 and CD71 (expressed as coefficient of variation), in combination with CD71 fluorescence intensity and the percentage of CD117+ erythroid progenitors provided the best discrimination between myelodysplastic syndromes and non-clonal cytopenias (specificity 90%; 95% confidence interval: 84-94%). The high specificity of this marker set was confirmed in the validation cohort (92%; 95% confidence interval: 86-97%). This erythroid flow cytometry marker combination may improve the evaluation of cytopenic cases with suspected myelodysplasia, particularly when combined with flow cytometry assessment of the myelomonocytic lineage.

Multicentric study underlining the interest of adding CD5, CD7 and CD56 expression assessment to the flow cytometric Ogata score in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms.

Although numerous recent publications have demonstrated interest in multiparameter flow cytometry in the investigation of myelodysplastic disorders, it is perceived by many laboratory hematologists as difficult and expensive, requiring a high level of expertise. We report a multicentric open real-life study aimed at evaluating the added value of the technically simple flow cytometry score described by the Ogata group for the diagnosis of myelodysplastic syndromes. A total of 652 patients were recruited prospectively in four different centers: 346 myelodysplastic syndromes, 53 myelodysplastic/myeloproliferative neoplasms, and 253 controls. The Ogata score was assessed using CD45 and CD34 staining, with the addition of CD10 and CD19. Moreover, labeling of CD5, CD7 and CD56 for the evaluation of myeloid progenitors and monocytes was tested on a subset of 294 patients. On the whole series, the specificity of Ogata score reached 89%. Respective sensitivities were 54% for low-risk myelodysplastic syndromes, 68% and 84% for type 1 and type 2 refractory anemia with excess of blasts, and 72% for myelodysplastic/myeloproliferative neoplasms. CD5 expression was poorly informative. When adding CD56 or CD7 labeling to the Ogata score, sensitivity rose to 66% for low-risk myelodysplastic syndromes, to 89% for myelodysplastic/myeloproliferative neoplasms and to 97% for refractory anemia with excess of blasts. This large multicenter study confirms the feasibility of Ogata scoring in routine flow cytometry diagnosis but highlights its poor sensitivity in low-risk myelodysplastic syndromes. The addition of CD7 and CD56 in flow cytometry panels improves the sensitivity but more sophisticated panels would be more informative.

Circulating immature granulocytes with T-cell killing functions predict sepsis deterioration*.

OBJECTIVES: Primary objective was to identify leukocyte subsets that could predict the early evolution of sepsis at 48 hours (i.e., deterioration or stability/improvement). Secondary objectives were to evaluate the prognostic value of leukocyte subsets on mortality and immunosuppressive properties of immature granulocytes. DESIGN: Twenty-three peripheral blood leukocyte subsets were analyzed using a new-generation 10-color flow cytometry. T-cell killing activity of immature granulocytes was explored using a sorting method specifically developed. SETTING: ICUs and emergency departments. PATIENTS: All patients admitted to emergency department and ICU for sepsis ongoing for less than 24 hours were eligible. Exclusion criteria were pregnancy, age less than 18 years, solid tumors, HIV infection, hematological or inflammatory conditions, and immunosuppressive drugs. Finally, 177 patients were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The two most salient features of sepsis were decreased CD10 (CD10) and CD16 (CD16) expressions on granulocytes. With a threshold of 90% of CD10 and 15% of CD16 granulocytes, these immunophenotypic features, which are those of immature granulocytes, predicted sepsis deterioration at 48 hours with a sensitivity of 57% and 70% and a specificity of 78% and 82%, respectively. Survival rate at day 30 was 99% for patients without CD10 and CD16, 85% for patients with increased CD16 only, and 63% for patients with increased CD16 and CD10 granulocytes (p < 0.001). Among CD16 immature granulocytes, we identified a CD14/CD24 myeloid-derived suppressor cell subset with the capability of killing activated T cells. Consistently, an excess of CD16 immature granulocytes was associated with both CD3 and CD4 T-cell lymphopenia in deteriorating patients. CONCLUSIONS: Circulating immature granulocytes predicted early sepsis deterioration and were enriched in myeloid-derived suppressor cells which could be responsible for immunosuppression through the induction of T-cell lymphopenia.

Comparable flow cytometry data can be obtained with two types of instruments, Canto II, and Navios. A GEIL study.

Flow cytometry (FC) instruments settings classically rely on local establishment of photomultipliers (PMT) voltages adapted to the measurements expected to be performed. In the era of multiparameter FC (MFC), it appears more and more desirable that comparable patterns of fluorescence are obtained in different settings. This relies on a harmonization of settings between instruments. Although this has been shown to be feasible within a given brand of flow cytometers, little information is available about broader comparisons in a given center or in a multicenter fashion. Here, we report a two-phase series of experiments first performed between a Canto II (BD Biosciences) and a Navios (Beckman Coulter) instruments in the same center. PMT values adjusted on the reference instrument (RI) Canto II were used to establish target values for PMT settings on the paired Navios practice instrument (PI). This allowed to show the good correlation of all but peaks 1 and 2 of Rainbow(®) beads between RI and PI. Using 4- or 8-color stained leukocytes, the similitude of the settings was further confirmed. A complex set of matrices was then established between five centers all equipped with both instruments. Using Bland & Altman difference comparisons for median fluorescence values, it was shown that using either Rainbow beads or CD16 stained polymorphonuclears to set-up target values on the RI CantoII, highly superimposable results could be obtained on all 9 PI. The latter were obtained using Rainbow beads or Compbeads(®) for comparisons. In summary, this two-phase study demonstrates the feasibility of different methods allowing for a robust harmonization of settings for MFC.

Very low levels of surface CD45 reflect CLL cell fragility, are inversely correlated with trisomy 12 and are associated with increased treatment-free survival.

It has recently been suggested that the percentage of smudge cells on blood smears from patients with chronic lymphocytic leukemia (CLL) could predict overall survival. However, smudge cells are a cytological artifact influenced by multiple physical factors not related to CLL. To identify simple parameters reflecting CLL cell fragility, we studied CD45 expression in a series of 66 patients with Binet stage A CLL. Decreased CD45 expression was specific for CLL cells when compared to 44 patients with a leukemic phase of B-cell non Hodgkin lymphoma and 42 control B-cells. CD45 expression was markedly decreased for all patients with CLL with high percentages of smudge cells. CLL cells with the lowest CD45 expression were the most sensitive to osmotic shock. Very low levels of CD45 expression were significantly associated with lack of CD38 expression, absence of trisomy 12, and with increased treatment free survival time. Altogether, these results demonstrate that low levels of CD45 expression are specific to CLL cells and reflect cell fragility, suggesting that this is an important intrinsic biological feature that determines disease course.

T/B ratio does not reflect levels of ZAP70 expression in clonal CLL B-cells due to ZAP70 overexpression in patient T-cells.

Flow cytometry is the reference technique for assessing ZAP70 expression, a marker of poor prognosis in CLL. One of the most common methods is to assess ZAP70 levels in CLL cells by calculating the ratio between ZAP70 mean fluorescence intensities (MFIs) in residual T-cells and CLL B-cells (ZAP70 T/B ratio). In this study, we developed a new method for ZAP70 labeling. Cells were labeled with a combination of anti ZAP70 phycoerythrin-conjugated SBZAP monoclonal antibody (mAb) and mAbs against CD45, CD19, and CD5. The latter three were used to specifically gate on different lymphocyte subsets. Staining was performed in absence (test) or in presence of excess unconjugated SBZAP mAb (isoclonic control). A so-called ZAP70 isoclonic ratio between SBZAP MFIs in the test and isoclonic control was calculated. A series of 32 patients with CLL and 10 normal controls were studied. Prediction of IGHV mutation status by ZAP70 isoclonic and T/B ratios was similar. By using the ZAP70 isoclonic ratio, we showed that ZAP70 expression was increased in T-cells from CLL patients. Nearly all cases with increased ZAP70 expression in CLL cells were associated with high ZAP70 expression in cognate T-cells. Therefore, the ZAP70 isoclonic ratio was more likely to closely reflect the biology of ZAP70 dysregulation rather than the T/B ratio. These results also explained why ZAP70 T/B ratios were artefactually close to normal in cells from CLL patients with high levels of ZAP70.

Potent graft-versus-leukemia effect after reduced-intensity allogeneic SCT for intermediate-risk AML with FLT3-ITD or wild-type NPM1 and CEBPA without FLT3-ITD.

To investigate the role of reduced-intensity allogeneic (RIC-allo) stem cell transplant (SCT) as postremission therapy in adult intermediate-risk patients with acute myelogenous leukemia (AML) with FLT3-ITD or wild-type NPM1 and CEBPA without FLT3-ITD, we conducted a single-center retrospective study between January 2001 and December 2010. Sixty-six patients were included: 37 treated with RIC-alloSCT and 29 with nonallogeneic SCT therapies. Both groups were comparable concerning age, WBC count at diagnosis, gender, karyotype, genotype, and number of courses of chemotherapy to reach complete remission (CR1). Median follow-up after CR1 was 37 months (range, 11-112 months) and 48 months (range, 9-83 months) in the allo and no-allo groups, respectively. In the allo versus no-allo groups, the 3-year cumulative incidence of relapse (CIR) rates were 25% ± 8% versus 61% ± 9%; P = .005. The 3-year nonrelapse mortality (NRM), overall survival (OS), and relapse-free survival (RFS) were 22% ± 7% versus 4% ± 4% (P = .005), 52% ± 9% versus 44% ± 10% (P = .75), and 53% ± 9% versus 35% ± 9% (P = .28), respectively. Multivariate analysis indicated that CIR was reduced by allo (hazard ratio [HR], 0.32; P = .01). A landmark analysis performed at day 185 after CR1 confirmed a lower CIR after allo. RIC-allo reduces the risk of relapse, suggesting a potent graft-versus-leukemia (GVL) effect in these patients at a high risk of relapse.