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Background: The measurement of minimal residual disease (MRD) by multiparametric flow cytometry (MFC) before hematopoietic stem cell transplantation (HSCT) in patients with acute myeloid leukemia (AML) is a powerful prognostic factor. The interaction of pretransplant MRD and the conditioning intensity has not yet been clarified. Objective: The aim of this study is to analyze the transplant outcomes of patients with AML who underwent HSCT in complete remission (CR), comparing patients with positive MRD (MRD+) and negative MRD (MRD-) before HSCT, and the interaction between conditioning intensity and pre-HSCT MRD. Study design: We retrospectively analyzed the transplant outcomes of 118 patients with AML who underwent HSCT in CR in a single institution, comparing patients with MRD+ and MRD- before HSCT using a cutoff of 0.1% on MFC, and the interaction between conditioning intensity and pre-HSCT MRD. Results: Patients with MRD+ before HSCT had a significantly worse 2-year (2y) event-free survival (EFS) (56.5% vs. 32.0%, p = 0.018) than MRD- patients, due to a higher cumulative incidence of relapse (CIR) at 2 years (49.0% vs. 18.0%, p = 0.002), with no differences in transplant-related mortality (TRM) (2y-TRM, 19.0% and 25.0%, respectively, p = 0.588). In the analysis stratified by conditioning intensity, in patients who received MAC, those with MRD- before HSCT had better EFS (p = 0.009) and overall survival (OS) (p = 0.070) due to lower CIR (p = 0.004) than MRD+ patients. On the other hand, the survival was similar in reduced intensity conditioning (RIC) patients regardless of the MRD status. Conclusions: Patients with MRD+ before HSCT have worse outcomes than MRD- patients. In patients who received MAC, MRD- patients have better EFS and OS due to lower CIR than MRD+ patients, probably because they represent a more chemo-sensitive group. However, among RIC patients, results were similar regardless of the MRD status. [ABSTRACT FROM AUTHOR]

BackgroundThe measurement of minimal residual disease (MRD) by multiparametric flow cytometry (MFC) before hematopoietic stem cell transplantation (HSCT) in patients with acute myeloid leukemia (AML) is a powerful prognostic factor. The interaction of pretransplant MRD and the conditioning intensity has not yet been clarified.ObjectiveThe aim of this study is to analyze the transplant outcomes of patients with AML who underwent HSCT in complete remission (CR), comparing patients with positive MRD (MRD+) and negative MRD (MRD−) before HSCT, and the interaction between conditioning intensity and pre-HSCT MRD.Study designWe retrospectively analyzed the transplant outcomes of 118 patients with AML who underwent HSCT in CR in a single institution, comparing patients with MRD+ and MRD− before HSCT using a cutoff of 0.1% on MFC, and the interaction between conditioning intensity and pre-HSCT MRD.ResultsPatients with MRD+ before HSCT had a significantly worse 2-year (2y) event-free survival (EFS) (56.5% vs. 32.0%, p = 0.018) than MRD− patients, due to a higher cumulative incidence of relapse (CIR) at 2 years (49.0% vs. 18.0%, p = 0.002), with no differences in transplant-related mortality (TRM) (2y-TRM, 19.0% and 25.0%, respectively, p = 0.588). In the analysis stratified by conditioning intensity, in patients who received MAC, those with MRD− before HSCT had better EFS (p = 0.009) and overall survival (OS) (p = 0.070) due to lower CIR (p = 0.004) than MRD+ patients. On the other hand, the survival was similar in reduced intensity conditioning (RIC) patients regardless of the MRD status.ConclusionsPatients with MRD+ before HSCT have worse outcomes than MRD− patients. In patients who received MAC, MRD− patients have better EFS and OS due to lower CIR than MRD+ patients, probably because they represent a more chemo-sensitive group. However, among RIC patients, results were similar regardless of the MRD status.

Background: Cytogenetic analysis continues to have an important role in the management of acute myeloid leukemia (AML) because it is essential for prognostication. It is also necessary to diagnose specific categories of AML and to determine the most effective form of treatment. Reports from South Asia are few because the availability of cytogenetic services is relatively limited. Methods: We performed a retrospective analysis of the cytogenetic findings in adults with AML seen consecutively in a single centre in India. The results were categorised according to the 2022 World Health Organisation (WHO), International Consensus Classification (ICC) and European LeukemiaNet (ELN) classifications. Results: There were 1791 patients aged 18–85 years (median age 42, 1086 males). Normal karyotypes were seen in 646 (36%) patients. The 1145 (64%) abnormal karyotypes comprised 585 (32.7%) with recurrent genetic abnormalities (RGA), 403 (22.5%) with myelodysplasia-related cytogenetic abnormalities (MRC), and 157 (8.8%) with other abnormalities. There were 567 (31.7%) patients with solitary abnormalities and 299 (16.7%) with two abnormalities. Among the 279 (15.6%) patients with ≥ 3 abnormalities, 200 (11.2%) had complex karyotypes (CK) as per the WHO/ICC and 184 (10.3%), as per the ELN definition. There were 158 (8.8%) monosomal karyotypes (MK). Patients with normal karyotypes had a higher median age (45 years) than those with abnormal karyotypes (40 years, p < 0.001), and those with ≥ 3 abnormalities (43 years), than those with fewer abnormalities (39 years, p = 0.005). Patients with CK (WHO/ICC) and monosomal karyotypes had a median age of 48 years. Those with RGA had a lower median age (35 years, p < 0.001) than MRC (46 years) or other abnormalities (44 years). The t(15;17) was the most common abnormality (16.7%),followed by trisomy 8 (11.6%), monosomy 7/del 7q (9.3%), t(8;21) (7.2%), monosomy 5/del 5q (6.7%) and monosomy 17/del 17p (5.2%). Conclusion: Our findings confirm the lower age profile of AML in India and show similarities and differences with respect to the frequencies of individual abnormalities compared to the literature. The frequencies of the t(15;17), trisomy 8 and the high-risk abnormalities monosomy 7 and monosomy 5/del 5q were higher, and that of the inv(16), lower than in most reports. [ABSTRACT FROM AUTHOR]

Summary: To evaluate the prognostic impact of complex karyotype (CK) and/or monosomal karyotype (MK) in combination with various clinical factors on allogeneic stem cell transplantation (HSCT) outcomes of patients with acute myeloid leukaemia (AML), we analysed the registry database of adult AML patients who underwent allogeneic HSCT between 2000 and 2019 in Japan. Among 16 094 patients, those with poor cytogenetic risk (N = 3345) showed poor overall survival (OS) after HSCT (25.3% at 5 years). Multivariate analyses revealed that CK and/or MK (hazard ratio [HR], 1.31 for CK without MK; 1.27 for MK without CK; and 1.73 for both), age at HSCT ≥50 years (HR, 1.58), male sex (HR, 1.40), performance status ≥2 (HR, 1.89), HCT‐CI score ≥3 (HR, 1.23), non‐remission status at HSCT (HR, 2.49), and time from diagnosis to HSCT ≥3 months (HR, 1.24) independently reduced post‐HSCT OS among patients with poor cytogenetic risk AML. A risk scoring system based on the multivariate analysis successfully stratified patients into five distinct groups for OS. This study confirms the negative effects of CK and MK on post‐HSCT outcomes, and offers a powerful risk scoring system for predicting prognoses after HSCT among AML patients with unfavourable cytogenetics. [ABSTRACT FROM AUTHOR]

Background: Although monosomal karyotype (MK) has been recognized as an adverse risk factor in adult acute myeloid leukemia (AML), its impact on pediatric AML outcomes remains unclear. Methods: Clinical characteristics, cytogenetic and molecular profiling, and prognostic impact of MK were analyzed in a cohort of 284 children with AML in a Chinese population. Results: MK was present in 14 (4.5%) cases of the study cohort. MK-AML showed low prevalence of TP53 mutant and 17p13 aberrations. Children with MK-AML had shorter overall survival (OS) and event-free survival (EFS) compared to those with intermediate-risk features (OS: 26 ± 9.7% vs. 2 ± 1.5%, p

Introduction: Adult acute myeloid leukaemia (AML) patients with complex karyotype (CK) generally have unfavourable outcomes. CK commonly co‐exists with characteristic chromosomal and genetic abnormalities such as monosomal karyotype (MK), −17 or 17p‐ [abn(17p)] and TP53 mutations. Their individual prognostic significance needs to be clarified. Methods: Seventy‐three adult CK‐AML patients and eleven adult non‐CK‐AML patients with TP53 mutations (non‐CK/TP53mu) who were diagnosed and received therapy at our institute were enrolled. One hundred and fifty‐seven AML cases retrieved from the cancer genome atlas (TCGA) for validation. Results: Among CK‐AML patients, those with TP53 mutations (CK/TP53mu) had significantly lower rates of 1‐course induction complete remission (CR), 2‐year relapse‐free survival (RFS) and 2‐year overall survival (OS) than those without TP53 mutations (CK/TP53wt); whereas, abn(17p) did not have the above impacts; MK was significantly associated with a lower 2‐year OS rate but was not related to the rates of CR and RFS. Multivariate analysis showed that it were TP53 mutations and treating with chemotherapy alone but not MK and abn(17p) that independently predicted the adverse prognosis for RFS and OS in CK‐AML. Furthermore, non‐CK/TP53mu patients showed similar rates of CR, RFS and OS to CK/TP53mu patients. Validation using the TCGA cohort showed that CK/TP53mu patients had a significantly lower 2‐year OS rate than CK/TP53wt patients, whereas abn(17p) and MK did not impact OS; the 2‐year OS rate of patients with CK/TP53wt was similar to that of patients with intermediate‐risk cytogenetics. Conclusion: Adult CK‐AML patients have varied risks and TP53 mutations seem to be an independent adverse prognostic factor. [ABSTRACT FROM AUTHOR]

We investigated the impact of patient and disease characteristics, including cytogenetics, previous therapy, and depth of response, on the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) for patients with myelodysplastic syndrome (MDS). We analyzed 256 MDS patients who underwent transplantation from a matched related (n = 133) or matched unrelated (n = 123) donor after 2001. Of the 256, 78 (30.5%) did not receive cytoreductive therapy before HSCT; 40 (15.6%) received chemotherapy, 122 (47.7%) received hypomethylating agents (HMA), and 16 (6.2%) received both (chemo+HMA). Disease status at HSCT defined by International Working Criteria was complete remission in 46 (18%) patients. There were significant differences between therapy groups: there were more therapy-related MDS and higher use of matched related donor in the untreated group. The chemotherapy group had higher serum ferritin levels at HSCT. Patients were older and had more high-risk disease by revised International Prognostic Scoring in the HMA group. Despite those differences, transplantation outcomes were similar in patients who were untreated and who received cytoreductive therapy before HSCT. Three-year event-free survival (EFS) was 44.2%, 30.6%, 34.2%, and 32.8% for untreated, chemotherapy, HMA, and chemo+HMA groups, respectively (P = .50). Multivariate analyses revealed that older age (hazard ratio [HR], 1.3; P = .001); high-risk histologic subtypes, including refractory anemia with excess blasts (HR, 1.5; P = .05) and chronic myelomonocytic leukemia (HR, 2.1; P = .03), high-risk cytogenetics with monosomal karyotype (MK) (HR, 4.0; P

Background. Myelodisplastic syndromes (MDS) are a heterogeneous group of clonal hematological diseases and are not associated with specific chromosomal aberrations. The aim of the study is to identify the most significant immunophenotypic aberrations as criteria for the prognosis of the disease based on their relationship with the cytogenetic characteristics of blast cells of the bone marrow in patients with primary MDS. Material and methods. The study included 116 adult patients with MDS. The expression of antigens on bone marrow blast cells was determined by the method of eight-color flow cytofluorimetry. The study of the karyotype was performed using the standard GTG method. Results. The presence of aberrant expression of CD56 and a decrease in the expression of CD38 on blast cells have been found to be associated with the presence of prognostically significant chromosomal abnormalities -7 / del (7q-), -5 / del (5q-). It has been proved that aberrant expression of CD25, CD5, CD19 and a decrease or lack of CD34 expression on blast cells correlate with monosomy 8, 9, and 20 chromosomes involved in the monosomal karyotype. Conclusion. A statistical relationship between immunophenotypic aberrations and certain cytogenetic disorders with different prognostic significance was revealed.

• Effect of acute myeloid leukemia karyotype on the outcomes of allogeneic stem cell transplantation was tested. • Cytogenetic evolution affects prognosis after allogeneic stem cell transplantation. Recent progress in genetic analysis technology has helped researchers understand the pathogenesis of acute myeloid leukemia (AML). Considering this progress, AML karyotype is still one of the most significant prognostic factors that provides risk-adapted treatment approaches. Karyotype changes during treatment have been observed at times, but their prognostic impact is sparse, especially on allogeneic stem cell transplantation (allo-SCT). Here, we retrospectively investigated the effect of chromosomal changes between diagnosis and pretransplantation on the prognosis of allo-SCT by analyzing the outcomes of 212 consecutive patients who underwent allo-SCT for the first time at Toranomon Hospital, Tokyo, Japan, between 2008 and 2018. Cytogenetic abnormalities at diagnosis and pretransplantation were categorized based on the 2017 European Leukemia Net risk stratification. Genetic abnormalities such as FLT3-ITD and NPM1 were not considered in this study due to lack of genetic information in most patients. We defined cytogenetic evolution as chromosomal changes classified from lower category to higher category. Seventeen patients (8%) had cytogenetic evolution between diagnosis and pretransplantation, and they showed a significantly worse relapse rate than those who were categorized in the intermediate group based on the karyotype at diagnosis (3-year confidence interval [CI] of relapse, 57.4% versus 24.9%; P <.01). In multivariate analysis, cytogenetic evolution before allo-SCT had a significant impact on the CI of relapse (hazard ratio [HR], 3.89; CI, 1.75 to 8.67; P <.01), as well as the high score of the hematopoietic cell transplantation-specific comorbidity index (HR, 0.54; CI, 0.31 to 0.94; P =.03), but had no significant impact on overall survival or nonrelapse mortality. These results indicate that cytogenetic evolution has a significant impact after allo-SCT and should be considered during AML treatment. [ABSTRACT FROM AUTHOR]

Objectives: We evaluated the prognostic impact of MK on postremission outcomes of AML patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) in the first complete remission (CR1). Methods: We retrospectively analyzed 465 adult patients with AML who had received HSCT in the first CR between 2000 and 2016. Results: In MK + AML, the median leukocyte count was significantly lower (P <.001) and no NPM1 mutation was found (P =.042). Multivariate analysis revealed that MK was the most powerful prognostic factors for OS (hazard ratio [HR], 2.6; P =.001), EFS (HR, 3.8; P <.001), and cumulative incidence of relapse (HR, 6.1; P <.001), compared to any other poor risk factors such as complex karyotype, FLT3‐ITD mutations, old age, and higher leukocyte count. The adverse prognostic impact of MK tended to be more prominent in the younger age group (<40 years) (HR, 6.3, P <.001) than in the older age group (≥40 years) (HR, 3.4, P <.001). Conclusion: Novel treatment modalities for MK + AML need to be investigated to reduce the risk of relapse after HSCT. [ABSTRACT FROM AUTHOR]

Monosomal karyotype (MK) is associated with poor prognosis in patients with myeloid neoplasms; however, its prognostic significance in Philadelphia chromosome-negative (Ph-negative) acute lymphoblastic leukemia (ALL) remains unclear. Data of 323 patients with Ph-negative ALL treated at Peking University People's Hospital were retrospectively analyzed. MK was identified in 49 (14.8%) patients. The patients with MK had lower hemoglobin levels (P = 0.026), lower platelet count (P = 0.032), higher percentages of blasts in the peripheral blood at diagnosis (P = 0.008), and higher percentages of high-risk karyotypes (P < 0.001) compared with those without MK. The complete remission (CR) rate and the minimal residual disease negativity rate were not significantly different between patients with and without MK. In the multivariate analysis, MK was identified as an independent factor associated with higher cumulative incidence of relapse (CIR) (hazard ratio (HR), 2.07; 95% confidence interval (CI), 1.02, 4.21; P = 0.043), shorter disease-free survival (DFS) (HR, 2.80; 95% CI, 1.20, 6.54; P = 0.017) and shorter overall survival (OS) (HR, 5.75; 95% CI, 2.07, 16.03; P = 0.001) in the chemotherapy cohort; however, MK had no impact on outcomes in the allogeneic hematopoietic stem cell transplantation (allo-HSCT) cohort. Mantel-Byar analysis showed that allo-HSCT was associated with lower CIR (P < 0.001), longer DFS (P < 0.001), and longer OS (P < 0.001) in CR patients with MK. In conclusion, our study showed that MK was an independent predictor of poor outcomes in patients with Ph-negative ALL receiving chemotherapy but not allo-HSCT, and allo-HSCT could improve the outcomes of patients with MK. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to evaluate the clinical and molecular characteristics of myelodysplastic syndrome (MDS) patients with monosomal karyotype (MK). Methods: Eighty MDS patients with MK diagnosed between January 2010 and December 2018 were included in the retrospective study. Seventy‐three had complex karyotype (CK) and 46 had very CK (vCK, ≥ 5 abnormalities). Clinical information was collected, and a panel of 37 genes, on which mutations have been previously reported to be associated with MDS patients, was analyzed by next‐generation sequencing. Genetic and biological features and their association with survival were evaluated. Results: Monosomy 5, 7, and 17 were the most frequent and mainly occurred in patients with vCK. While median overall survival (OS) for all patients was 12.8 months with 95% CI 9.1‐16.5, patients with vCK had shorter OS (8.4 months with 95% CI 3.9‐12.8) than those with non‐vCK (16.1 months with 95% CI 11.5‐20.8) (P =.02). At least one gene mutation was detected in 76 patients (95%), TP53 mutations were detected in 57 patients, and their median OS was significantly shorter than those without TP53 mutations (9.5 months with 95% CI 7.5‐11.5 vs 26.1 months with 95% CI 8.0‐44.2, P <.01). In 34 patients who received treatment with decitabine, 25 with TP53 mutations had higher overall response rate than those with wild‐type TP53 (60% vs 22.2%, P =.03). However, OS was still significantly shorter in those with TP53 mutations (10.1 vs 26.1 months, P =.03). Multivariate analysis confirmed that TP53 mutations was an independent poor prognostic factor on OS. Conclusions: CK and vCK overlap in most of the MDS patients with MK. TP53 mutations occur more frequently in MDS patients with vCK, and both TP53 mutations and vCK are adverse prognostic factors. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the clinical characteristics and prognostic significance of monosomal karyotypes (MKs) in patients with acute myeloid leukemia (AML). Materials and Methods: We retrospectively analyzed the clinical data for 498 patients with AML, of whom 233 (46.8%) had an abnormal karyotype, including 42 with MKs (8.4%) and 70 with a complex karyotype (CK) (14.1%). Results: Patients with MKs were older (median age 62.5 vs. 52 years, p=0.003) and had lower median hemoglobin levels (62.5 vs. 77 g/L, p=0.009) and lower white blood cell counts (7.0×109/L vs. 11.7×109/L, p=0.008). Univariate analysis showed that patients with MKs or CKs had shorter overall survival than patients without these karyotypes (median survival time 7.3 vs. 26.3 months for MK, p

Introduction: The aim of the study was to analyze monosomal karyotype (MK) occurrence and the relationship between MKs and complex karyotypes (CKs) and to determine the prognostic significance of MKs in MDS patients based on conventional cytogenetic (CC) and fluorescence in situ hybridization (FISH) analyses. Methods: CC and FISH analyses were conducted for 216 primary MDS patients. Follow‐ups and statistical analysis were conducted. Results: A total of 25 (11.6%) patients with MKs were identified by FISH and CC analyses, and 23 (92%) of these MKs were also CKs. Only 19 patients (8.8%) with MKs were identified by CC analysis. Patients with MKs had higher bone marrow (BM) blast counts (P = 0.006), incidence of very high risk according to International Prognostic Scoring System‐Revised (IPSS‐R) (P < 0.001), leukemic transformation (P = 0.003,) and death rates (P < 0.001) than those without MKs. Overall survival (OS) and progression‐free survival (PFS) of MK or CK patients which were additionally detected by FISH and CC analyses had no statistical significance with those MK or CK patients detected by CC analyses separately. Multivariate analysis indicated that MK (P < 0.001), blast in BM (P < 0.001) and age (P = 0.028) were inferior independent prognostic factors in OS, whereas CK (P = 0.003) was the inferior independent prognostic factor in PFS. Conclusion: The MDS FISH panel may provide additional information for defining MKs beyond CC analysis. MK was an important indicator of OS in MDS patients, and CK indicated inferior disease progression but did not influence OS according to CC and FISH analyses. [ABSTRACT FROM AUTHOR]

Summary: Data on occurrence, genetic characteristics and prognostic impact of complex and monosomal karyotype (CK/MK) in children with acute myeloid leukaemia (AML) are scarce. We studied CK and MK in a large unselected cohort of childhood AML patients diagnosed and treated according to Nordic Society for Paediatric Haematology and Oncology (NOPHO)‐AML protocols 1993–2015. In total, 800 patients with de novo AML were included. CK was found in 122 (15%) and MK in 41 (5%) patients. CK and MK patients were young (median age 2·1 and 3·3 years, respectively) and frequently had FAB M7 morphology (24% and 22%, respectively). Refractory disease was more common in MK patients (15% vs. 4%) and stem cell transplantation in first complete remission was more frequent (32% vs. 19%) compared with non‐CK/non‐MK patients. CK showed no association with refractory disease but was an independent predictor of an inferior event‐free survival (EFS; hazard ratio [HR] 1·43, P = 0·03) and overall survival (OS; HR 1·48, P = 0·01). MK was associated with a poor EFS (HR 1·57, P = 0·03) but did not show an inferior OS compared to non‐MK patients (HR 1·14, P = 0·62). In a large paediatric cohort, we characterized AML with non‐recurrent abnormal karyotype and unravelled the adverse impact of CK and MK on prognosis. [ABSTRACT FROM AUTHOR]

This study aimed to validate the capability of the Center for International Blood and Marrow Transplant Research (CIBMTR) prognostic scoring system to predict outcomes of patients with myelodysplastic syndromes (MDS) who had undergone HLA-haploidentical related donor hematopoietic stem cell transplantation (haplo-HSCT). We also propose and validate a more suitable prognostic scoring system. A total of 157 patients with MDS who underwent haplo-HSCT were enrolled. The CIBMTR prognostic scoring system could predict the 2-year clinical outcomes, but failed to predict the 100-day clinical outcomes after haplo-HSCT. Our multivariable model identified 2 independent predictors of overall survival: age and monosomal karyotype (MK). Weighted scores of 5, 3, and 2 were assigned to age ≥50 years, age 30 to 49 years, and MK, respectively, and a 2-category system was created: low (score ≤3) and high (score >3). Our refined prognostic scoring system can predict both the 100-day and 2-year clinical outcomes after haplo-HSCT. Our findings indicate that the CIBMTR prognostic scoring system is predictive of the outcomes of patients with MDS following haplo-HSCT, and that older patients with MDS and/or patients with MK should be closely monitored after haplo-HSCT. [ABSTRACT FROM AUTHOR]

The presence of a monosomal karyotype (MK+) and/or a complex karyotype (CK+) identifies subcategories of AML with poor prognosis. The prognostic significance of the most common monosomies (monosomy 5, monosomy 7, and monosomy 17) within MK+/CK+ AML is not well defined. We analyzed data from 1,592 AML patients age 17–93 years enrolled on ECOG-ACRIN therapeutic trials. The majority of MK+ patients (182/195; 93%) were MK+/CK+ with 87% (158/182) having ≥5 clonal abnormalities (CK≥ 5). MK+ patients with karyotype complexity ≤4 had a median overall survival (OS) of 0.4y compared to 1.0y for MK- with complexity ≤4 (p < 0.001), whereas no OS difference was seen in MK+ vs. MK- patients with CK≥ 5 (p = 0.82). Monosomy 5 (93%; 50/54) typically occurred within a highly complex karyotype and had no impact on OS (0.4y; p = 0.95). Monosomy 7 demonstrated no impact on OS in patients with CK≥ 5 (p = 0.39) or CK ≤ 4 (p = 0.44). Monosomy 17 appeared in 43% (68/158) of CK≥ 5 patients and demonstrated statistically significant worse OS (0.4y) compared to CK≥ 5 patients without monosomy 17 (0.5y; p = 0.012). Our data suggest that the prognostic impact of MK+ is limited to those with less complex karyotypes and that monosomy 17 may independently predict for worse survival in patients with AML. [ABSTRACT FROM AUTHOR]

Monosomal karyotype (MK) and complex karyotype (CK) are poor prognostic factors in acute myeloid leukemia (AML). A comprehensive analysis of cytogenetic and clinical factors influencing an outcome of AML-CK+ was performed. The impact of cladribine containing induction on treatment results was also evaluated. We analyzed 125 patients with AML-CK+ treated within PALG protocols. MK was found in 75 (60%) individuals. The overall complete remission (CR) rate of 66 intensively treated patients was 62% vs. 28% in CK+ MK−and CK+ MK+ group (p = .01). No difference in CR rate was observed between DA and DAC arms. The overall survival (OS) in intensively treated patients was negatively influenced by MK, karyotype complexity (≥5 abnormalities), and WBC >20 G/L in multivariate analysis. The addition of cladribine to DA regimen improved OS only in MK−but not in MK+ group. In conclusion, concomitance of MK with ≥5 chromosomal abnormalities is associated with dismal treatment outcome in AMK-CK+. [ABSTRACT FROM AUTHOR]

In 2008, the concept of the monosomal karyotype (MK) in adult acute myeloid leukemia (AML) patients was introduced, defined by the presence of a chromosomal aberration pattern characterized by the presence of at least two autosomal monosomies or of one monosomy plus one or more structural aberrations (not including loss of a chromosome). We present a systematic review of the literature about the influence of the MK on the outcome of patients affected by myeloid malignancies (AML, myelodysplastic syndromes, and primary myelofibrosis). For this review, a comprehensive literature search using the term "monosomal karyotype" was performed, considering articles listed in MEDLINE. This analysis of the literature confirms the negative prognostic impact on survival of the MK in myeloid neoplasias. The detrimental effect of MK on AML patients' outcome is independent of other variables, including adverse cytogenetic features, supporting the identification of this entity as a challenging subgroup of patients with distinct biologic and clinical features. [ABSTRACT FROM AUTHOR]

Introduction: Individuals who are exposed to cytotoxic agents are at risk of developing therapy-related myeloid neoplasms (t-MN). Cytogenetic findings of a neoplasm play an important role in stratifying patients into different risk groups and thus predict the response to treatment and overall survival. Case report: A 59-year-old man was diagnosed with acute promyelocytic leukaemia. Following this, he underwent all-trans retinoic acid (ATRA) based chemotherapy and achieved remission. Four years later, the disease relapsed and he was given idarubicin, mitoxantrone and ATRA followed by maintenance chemotherapy (ATRA, mercaptopurine and methotrexate). He achieved a second remission for the next 11 years. During a follow-up later, his full blood picture showed leucocytosis, anaemia and leucoerythroblastic picture. Bone marrow examination showed hypercellular marrow with trilineage dysplasia, 3% blasts but no abnormal promyelocyte. Fluorescence in-situ hybridisation (FISH) study of the PML/RARA gene was negative. Karyotyping result revealed complex abnormalities and monosomal karyotype (MK). A diagnosis of therapy-related myelodysplastic syndrome/myeloproliferative neoplasm with unfavourable karyotypes and MK was made. The disease progressed rapidly and transformed into therapy-related acute myeloid leukaemia in less than four months, complicated with severe pneumonia. Despite aggressive treatment with antibiotics and chemotherapy, the patient succumbed to the illness two weeks after the diagnosis. Discussion and Conclusion: Diagnosis of t-MN should be suspected in parents with a history of receiving cytotoxic agents. Karyotyping analysis is crucial for risk stratification as MK in addition to complex aberrant karyotypes predicts unfavourable outcome. Further studies are required to address the optimal management for patients with t-MN. [ABSTRACT FROM AUTHOR]

Monosomal karyotype (MK) is known as a far end of the unfavorable cytogenetics in adult acute myeloid leukemia (AML), while available data in childhood AML is scarce. In this study, we investigated the prevalence and prognostic value of MK with retrospectively analyzed 119 patients newly diagnosed with childhood de novo AML. Ten patients (8.4%) revealed to have MK. All MK-positive (MK(+)) AML were associated with complex cytogenetic abnormalities and belonged to the cytogenetic adverse-risk group. Nine of MK(+) patients (90%) achieved complete remission. The event-free survival (EFS) and overall survival (OS) of MK(+) adverse group were comparable to the ESF and OS of MK-negative non-adverse group (EFS 60.0 ± 15.5% vs 59.0 ± 5.1%, P = 0.925; OS 70.0 ± 14.5% vs 58.1 ± 5.3%, P = 0.696). In multivariate analysis, MK was not an independent adverse prognostic factor for EFS (hazard ratio 0.45, 95% C.I. 0.13–1.50, P = 0.194). In addition, 7 of 9 MK(+) patients who received allogeneic hematopoietic stem cell transplantation (HSCT) survived event-free, with a median follow-up of 64 months. In conclusion, MK did not act as an adverse prognostic factor in childhood de novo AML. Allogeneic HSCT might have contributed to the excellent outcome of MK(+) childhood de novo AML. [ABSTRACT FROM AUTHOR]

The plethora of knowledge gained on myelodysplastic syndromes (MDS), a heterogeneous pre-malignant disorder of hematopoietic stem cells, through sequencing of several pathway genes has unveiled molecular pathogenesis and its progression to AML. Evolution of phenotypic classification and risk-stratification based on peripheral cytopenias and blast count has moved to five-tier risk-groups solely concerning chromosomal aberrations. Increased frequency of complex abnormalities, which is associated with genetic instability, defines the subgroup of worst prognosis in MDS. However, the independent effect of monosomal karyotype remains controversial. Recent discoveries on mutations in RNA-splicing machinery ( SF3B1, SRSF2, ZRSR2, U2AF1, U2AF2) ; DNA methylation ( TET2, DNMT3A, IDH1/2 ); chromatin modification ( ASXL1, EZH2 ); transcription factor ( TP53, RUNX1 ); signal transduction/kinases ( FLT3, JAK2 ); RAS pathway ( KRAS, NRAS, CBL, NF1, PTPN11 ); cohesin complex ( STAG2, CTCF, SMC1A, RAD21 ); DNA repair ( ATM, BRCC3, DLRE1C, FANCL ); and other pathway genes have given insights into the independent effects and interaction of co-occurrence of mutations on disease-phenotype. RNA-splicing and DNA methylation mutations appeared to occur early and are reported as ‘founder’ mutations in over 50% MDS patients. TET2 mutation, through altered DNA methylation, has been found to have independent prognostic response to hypomethylating agents. Moreover, presence of DNMT3A, TET 2 and ASXL1 mutations in normal elderly individuals forms the basis of understanding that accumulation of somatic mutations may not cause direct disease-development; however, cooperation with other mutations in the genes that are frequently mutated in myeloid and other hematopoietic cancers might result in clonal expansion through self-renewal and/or proliferation of hematopoietic stem cells. Identification of small molecules as inhibitors of epigenetic mutations has opened avenues for tailoring targeted drug development. The recommendations of a Clinical Advisory Committee is being considered by WHO for a revised classification of risk-groups of MDS, which is likely to be published in mid 2016, based on the new developments and discoveries of gene mutations. [ABSTRACT FROM AUTHOR]

Therapy-related myeloid neoplasms (t-MN) are a heterogeneous group of aggressive myeloid neoplasms that arise following exposure to various cytotoxic therapeutic agents and/or ionizing radiation for treatment of prior non-myeloid malignancy or autoimmune disease. Each therapeutic group has been associated with varying latency intervals from the time of therapy exposure to onset of t-MN, as well as certain recurrent genetic alterations. This review will focus on the molecular genetic alterations that have been described in t-MNs, as well as recent updates regarding diagnostic classification., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2023 Elsevier Inc. All rights reserved.)

The presence of monosomal karyotype (MK+) in acute myeloid leukemia (AML) is associated with dismal outcomes. We evaluated the impact of MK+ in AML (MK+AML, n = 240) and in myelodysplastic syndrome (MDS) (MK+MDS, n = 221) on hematopoietic cell transplantation outcomes compared with other cytogenetically defined groups (AML, n = 3360; MDS, n = 1373) as reported to the Center for International Blood and Marrow Transplant Research from 1998 to 2011. MK+ AML was associated with higher disease relapse (hazard ratio, 1.98; P < .01), similar transplantation-related mortality (TRM) (hazard ratio, 1.01; P = .90), and worse survival (hazard ratio, 1.67; P < .01) compared with those outcomes for other cytogenetically defined AML. Among patients with MDS, MK+ MDS was associated with higher disease relapse (hazard ratio, 2.39; P < .01), higher TRM (hazard ratio, 1.80; P < .01), and worse survival (HR, 2.02; P < .01). Subset analyses comparing chromosome 7 abnormalities (del7/7q) with or without MK+ demonstrated higher mortality for MK+ disease in for both AML (hazard ratio, 1.72; P < .01) and MDS (hazard ratio, 1.79; P < .01). The strong negative impact of MK+ in myeloid malignancies was observed in all age groups and using either myeloablative or reduced-intensity conditioning regimens. Alternative approaches to mitigate disease relapse in this population are needed. [ABSTRACT FROM AUTHOR]

In a study of elderly AML patients treated with the hypomethylating agent decitabine (DAC), we noted a surprisingly favorable outcome in the (usually very unfavorable) subgroup with two or more autosomal monosomies (MK2+) within a complex karyotype (Lübbert et al., Haematologica 97:393-401, 2012). We now analyzed 206 myelodysplastic syndrome (MDS) patients (88 % of 233 patients randomized in the EORTC/GMDSSG phase III trial 06011, 61 of them with RAEBt, i.e. AML by WHO) with cytogenetics informative for MK status.. Endpoints are the following: complete/partial (CR/PR) and overall response rate (ORR) and progression-free (PFS) and overall survival (OS). Cytogenetic subgroups are the following: 63 cytogenetically normal (CN) patients, 143 with cytogenetic abnormalities, 73 of them MK-negative (MK-), and 70 MK-positive (MK+). These MK+ patients could be divided into 17 with a single autosomal monosomy (MK1) and 53 with at least two monosomies (MK2+). ORR with DAC in CN patients: 36.1 %, in MK- patients: 16.7 %, in MK+ patients: 43.6 % (MK1: 44.4 %, MK2+ 43.3 %). PFS was prolonged by DAC compared to best supportive care (BSC) in the CN (hazard ratio (HR) 0.55, 99 % confidence interval (CI), 0.26; 1.15, p = 0.03) and MK2+ (HR 0.50; 99 % CI, 0.23; 1.06, p = 0.016) but not in the MK-, MK+, and MK1 subgroups. OS was not improved by DAC in any subgroup. In conclusion, we demonstrate for the first time in a randomized phase III trial that high-risk MDS patients with complex karyotypes harboring two or more autosomal monosomies attain encouraging responses and have improved PFS with DAC treatment compared to BSC. [ABSTRACT FROM AUTHOR]

BACKGROUND Conflicting data exist about the impact of a monosomal karyotype (MK) on overall survival (OS) for patients with myelodysplastic syndromes (MDSs) and particularly for those with a complex karyotype (CK). This study was aimed at determining whether an MK is associated with OS independently of the number of cytogenetic abnormalities (CAs) in a population-based MDS cohort. METHODS Cancer registry data on incident MDS cases were linked with cytogenetic data and hospital administrative data from 2000 to 2010 for the Australian state of Victoria. RESULTS Between 2000 and 2010, 1404 incident MDS cases with cytogenetic results were identified. A CK, defined as 3 or more abnormalities, was present in 126 (9%). A very complex karyotype (vCK), defined as 5 or more abnormalities, was present in 95 (7%). An MK was associated with worse OS in the whole cohort (median 6 vs 39 months, P < 0.001) including those with a coexisting CK (6 vs 17 months, P < 0.001) or vCK (6 vs 9 months, P = 0.02). After adjustments for the number of CAs, an MK remained independently associated with OS, although its effect size decreased with increasing cytogenetic complexity (hazard ratio for an MK, 4.81; 95% confidence interval, 3.08-7.52; hazard ratio for the number of CAs, 1.22; 95% confidence interval, 1.15-1.30; and hazard ratio for the interaction between an MK and CAs, 0.83; 95% confidence interval, 0.77-0.89). CONCLUSIONS These results support the clinical utility of an MK as an independent predictor of adverse outcomes for MDS patients, even among CK and vCK groups, although its prognostic effect decreases with increasing cytogenetic complexity. Cancer 2015;121:2892-2899. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

This study investigated the outcomes of allogeneic hematopoietic cell transplantation (allo-HCT) in acute myeloid leukemia (AML) patients with monosomal karyotypes (MK). A total of 114 AML patients who received allo-HCT were retrospectively analyzed. At the time of diagnosis, 13 patients were categorized with a favorable cytogenetic risk, 78 with an intermediate risk, and 23 with an adverse risk. MK was found in 12 patients among 23 with adverse cytogenetic risk. Pretransplant disease status was active disease in 5 cases (45.5%) in the adverse-risk without MK group, and 8 cases (66.7%) in the corresponding group with MK, 15 (19.2%) in the intermediate group and 4 (30.8%) in the favorable group. In multivariate analysis, active disease before transplant (hazard ratio, HR 3.913, p < 0.001), acute graft-versus-host disease (GVHD) ≥grade 2 (HR 1.908, p = 0.048) and chronic GVHD (HR 0.364, p = 0.001) affected overall survival (OS). The initial cytogenetic risk groups were not a significant risk factor for OS in allogeneic settings. The 2-year OS rate was 44.0 ± 15.9% without MK and 20.7 ± 17.9% with MK (p = 0.246). However, the OS rate was better for patients with chronic GVHD (p = 0.025). In conclusion, a survival benefit was observed for MK-positive patients with chronic GVHD in an allogeneic setting. However, the prognosis still remained poor for patients with MK. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Monosomal karyotype (MK) in acute myeloid leukemia (AML) is associated with an extremely poor outcome. The clinical significance of MK and the role of allogeneic hematopoietic cell transplantation (HCT) were evaluated in 749 Korean patients with newly diagnosed AML. MK was found in 9.3 % of patients and was more frequent in patients with advanced age or secondary AML. Patients with MK had significantly lower blood leukocyte counts and bone marrow blast percentages, and they had lower complete remission (CR) rate (43 %) and shorter median overall survival (OS) (6.5 months) and relapse-free survival (RFS) (10.0 months) than any other prognostic group. MK+ patients who received allogeneic HCT at the first CR had higher OS [hazard ratio (HR) 0.344, P = 0.018], RFS (HR 0.257, P = 0.006), and lower relapse probability (HR 0.264, P = 0.008) than those not receiving. This study's results confirmed poor outcomes for AML patients with MK and suggest that allogeneic HCT at the first CR may improve outcome. [ABSTRACT FROM AUTHOR]

Various cytogenetic risk scoring systems may determine prognosis for patients with myelodysplastic syndromes (MDS). We evaluated 4 different risk scoring systems in predicting outcome after allogeneic hematopoietic cell transplantation (alloHCT). We classified 124 patients with MDS using the International Prognostic Scoring System (IPSS), the revised International Prognostic Scoring System (R-IPSS), Armand's transplantation-specific cytogenetic grouping, and monosomal karyotype (MK) both at the time of diagnosis and at alloHCT. After adjusting for other important factors, MK at diagnosis (compared with no MK) was associated with poor 3-year disease-free survival (DFS) (27% [95% confidence interval, 12% to 42%] versus 39% [95% confidence interval, 28% to 50%], P = .02) and overall survival (OS) (29% [95% confidence interval, 14% to 44%] versus 47% [95% confidence interval, 36% to 59%], P = .02). OS but not DFS was affected by MK at alloHCT. MK frequency was uncommon in low-score R-IPPS and IPSS. Although IPSS and R-IPSS discriminated good/very good groups from poor/very poor groups, patients with intermediate-risk scores had the worst outcomes and, therefore, these scores did not show a progressive linear discriminating trend. Cytogenetic risk score change between diagnosis and alloHCT was uncommon and did not influence OS. MK cytogenetics in MDS are associated with poor survival, suggesting the need for alternative or intensified approaches to their treatment. [ABSTRACT FROM AUTHOR]

BACKGROUND The karyotype is a predictor of outcomes in adults with acute lymphoblastic leukemia (ALL). The unfavorable prognostic significance of complex karyotype (CK) has been reported, whereas the prognostic relevance of monosomal karyotype (MK) has not been consistently evaluated. We aimed to assess the prognostic value of CK and MK in adults with ALL treated with risk-adapted protocols of the Spanish PETHEMA Group. METHODS The karyotypes of 881 adult ALL patients treated according to the protocols of the PETHEMA Group between 1993 and 2012 were centrally reviewed. CK and MK were assessed according to Moorman's criteria, and Breem's criteria, respectively. Specific analyses according to the risk groups and to the presence of t(9:22) were performed. RESULTS Of 364 evaluable patients 33 (9.2%) had CK, and 68 of 535 evaluable patients (12.8%) had MK. Complete remission rate, remission duration, and overall survival were not significantly different according to the presence of CK or MK in the whole series, according to the B or T lineage, in the high-risk group, or in patients with t(9;22), regardless of imatinib treatment, and in patients who received chemotherapy alone or chemotherapy followed by stem cell transplantation CONCLUSIONS Our study shows that CK and MK were not associated with a worse prognosis in adult patients with ALL treated with risk-adapted or subtype-oriented protocols. In patients with Ph+ ALL, MK did not have an impact on prognosis irrespective of imatinib treatment. Cancer. © 0000 American Cancer Society Cancer 2014;120:3958-3964. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

Objectives: Acute myeloid leukemia (AML) with monosomal karyotype (MK) recently has been reported to be associated with worse outcome than the traditional complex karyotype. Methods: In this retrospective study of 111 patients with AML, we identified 14 patients with MK (13% of all patients with AML) using the definition proposed by Breems et al. Results: Five (36%) of these 14 patients had a loss of a single chromosome in the presence of other structural abnormalities, and nine (64%) had a loss of two or more autosomal chromosomes. Patients with AML-MK presented at an older age, with lower bone marrow blasts, and their blasts less frequently expressed CD34. Most patients with AML-MK had morphologic multilineage dysplasia and were predominantly subclassified as having AML with myelodysplasia-related changes (AML-MRC). Molecular analysis showed a significant absence of NPM1 and FLT3 in patients with AML-MK. Conclusions: Outcome data showed that patients with AML-MK had significantly worse overall survival, disease-free survival, and complete response compared with the rest of the patients with AML as well as within the AML-MRC group. [ABSTRACT FROM AUTHOR]

Abstract: Monosomal karyotype (MK) and complex karyotype (CK) are well known to be associated with a very poor clinical outcome in patients with acute myeloid leukemia (AML). However, whether or not the prognostic impact of MK and CK remains relevant for patients who have undergone allogeneic hematopoietic cell transplantation (allo-HCT) is still unclear. We retrospectively analyzed the status of MK and CK, as well as other clinical laboratory features, in 148 allo-HCT AML patients at our institution and correlated with their event-free survival (EFS) and overall survival (OS) after transplantation. MK and CK were identified in 14 (9%) and 19 (13%) cases, respectively. On univariate analysis, only age (≥60 years) and WBC count (≥15 × 109/L) were significant adverse predictors for EFS (P < .001 and P = .017, respectively) and OS (P = .002 and P = .021, respectively). MK, CK, and other relevant parameters analyzed did not affect the clinical outcome. Multivariable analysis confirmed that both older age and high WBC count were independent prognostic factors for a shorter OS (P = .001 and P = .003, respectively) and a shorter EFS (P < .001 and P = .001, respectively). Our results indicate that neither MK nor CK are high-risk factors in AML patients undergoing allo-HCT. [Copyright &y& Elsevier]

We retrospectively analyzed the impact of cytogenetic abnormalities grouped according to the monosomal karyotype ( MK) classification or the Southwest Oncology/Eastern Cooperative Oncology Group ( SWOG/ ECOG) definition in 263 patients with acute myeloid leukemia ( AML) who underwent allogeneic stem cell transplantation (allo SCT) in complete remission ( CR) at our center. Risk grouping using the MK criteria shows a highly significant difference in 5-yr overall survival ( OS) ranging between 67%, for the most favorable, and 32%, for the poorest risk group ( P = 0.001). Although similarly precise in predicting OS, the MK scheme better separates patients with respect to relapse incidence as compared to the SWOG/ ECOG grouping ( P = 0.0001 vs. P = 0.01). Notably, patients displaying non- MK abnormalities ( MK−) had a 5-yr relapse incidence identical to those cytogenetically normal ( CN), that is 24%. Multivariate analysis revealed that the MK classification is an independent prognosticator and superior in predicting OS (hazard ratios, HR 3.74, P = 0.01) and relapse incidence ( HR 3.74, P = 0.005) as compared to the SWOG/ ECOG criteria. Finally, subgroup analysis revealed that the prognostic capacity of the MK classification is highly significant in patients treated with standard myeloablative conditioning prior to allo SCT ( P = 0.0011 for OS, P = 0.0007 for relapse). In contrast, the MK grouping failed to predict OS or relapse incidence in patients treated with reduced intensity conditioning. Taken together, these results indicate that the MK classification is superior in predicting the overall outcome of patients with AML undergoing allo SCT in CR. Furthermore, our data suggest that the genetic risk profile of MK− and CN patients is mostly overlapping in this setting. [ABSTRACT FROM AUTHOR]

Few studies have evaluated granulocyte colony-stimulating factor (G-CSF) priming in elderly patients with intensively treated acute myeloid leukemia (AML), and no data are available for genetically defined AML subgroups. We provide long-term results (median follow-up 7.6 years) of a randomized trial in which 183 patients (median age 67 years) received G-CSF prior to (G-CSF priming) or after two cycles of induction chemotherapy. CR rates with G-CSF priming and G-CSF post-chemotherapy were comparable (57 vs. 67 %, p = 0.153), with overall survival (OS) probabilities of 14 vs. 17 % at 10 years. Induction mortality was significantly higher with G-CSF priming (23 vs. 10 %, p = 0.015), primarily in normal karyotype (NK) AML. In this subgroup, a trend for better relapse-free survival (RFS) was observed with G-CSF priming (44 vs. 22 % at 10 years, p = 0.074) but did not translate into an OS benefit. G-CSF priming had no impact on AML with FLT3-ITD and NPM mutations and did not improve outcome in patients with adverse cytogenetics. In a landmark analysis, late consolidation with autologous stem cell transplantation or a second consolidation cycle significantly improved RFS compared with one consolidation cycle (21.0 vs. 12.8 months, p = 0.046). Future studies on G-CSF priming should be restricted to NK AML and used only in post-remission therapy. [ABSTRACT FROM AUTHOR]

Abstract: Karyotype is a powerful prognostic factor for complete remission (CR) and overall survival (OS) in acute myelogenous leukemia (AML). Adverse-risk karyotype AML is now treated with intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) to overcome relapse. We attempted to stratify patients with this disease using a combination of known factors. We evaluated clinical correlates in 211 adults with AML and adverse-risk karyotypes. We divided the patients into several subgroups based on the number of chromosomal aberrations (NCAs), normal karyotype (NK) mosaicism, and monosomal karyotype (MK) status. CR rates and survival outcomes were compared among the subgroups, and the relapse rate was calculated in the allo-HSCT subgroup. The cutoff of NCA ≥5 showed the worst OS (P < .001) compared with NCA ≥3 or NCA ≥4 even after allo-HSCT. NK mosaicism significantly improved OS in both the NCA <5 (P = .024) and NCA ≥5 (P = .030) subgroups, but after allo-HSCT, it showed a favorable effect only in the NCA <5 subgroup. MK showed worse OS (P = .041), but there was no significantly worse effect after allo-HSCT compared with non-MK. Finally, we stratified patients into 4 subgroups, NCA ≥5 and NCA <5 with and without NK mosaicism. The most favorable OS and lower relapse rate after allo-HSCT were achieved by the NCA <5 with NK mosaicism subgroup, and the NCA ≥5 without NK mosaicism subgroup showed the worst prognosis in both entire group and allo-HSCT subgroup analysis. This study reveals that the combination of NCA and NK mosaicism may predict survival outcomes accurately, and suggests that novel treatment strategies for highly adverse-risk group AML should be tailored in the future. [Copyright &y& Elsevier]

Abstract: A monosomal karyotype (MK) was identified by banding techniques (BT) in acute myeloid leukemia (AML). However, BT may be insufficient to determine the actual loss of a complete chromosome, especially in complex karyotypes. We have investigated the effect of monosomy type, total (MK-t) and partial (MK-p), reevaluated by FISH, on prognosis. We have found that complete remission rate and probability of overall survival at 1 year was higher in MK-p (n =27) than MK-t (n =15) group (40% vs. 15.4%, P =0.19 and 30% vs. 9%, P =0.046, respectively). Our results indicate for the first time that monosomy type influences the prognosis of MK-AML. [Copyright &y& Elsevier]

Abstract: Several cytogenetic features, including monosomal karyotype (MK), have been associated with unfavorable prognosis in acute myeloid leukemia (AML). However, little is known about the prognostic significance of immunophenotypes in AML patients with unfavorable-risk cytogenetics. We evaluated immunophenotypes, cytogenetics, clinical features and survival outcomes in 233 uniformly treated AML patients who harbored unfavorable cytogenetics. CD11b expression was observed in 145 (70%) of 208 patients and emerged as an independent prognostic factor for inferior overall survival in multivariate analysis (p =0.024). MK and age≥60 years were predictors for lower complete remission rate (p =0.017, p <0.0001, respectively) and shorter overall survival (p =0.024, p <0.0001), while complex karyotype (CK) predicted a shorter overall survival (p =0.013). CD11b expression was strongly correlated with MK and identified a subset of patients with MK who had extremely poor overall survival. We proposed a prognostic scoring model using CD11b positivity, age≥60 years, the presence of MK and the presence of CK to classify the patients into distinct risk groups. We identified the poor prognosis of CD11b expression and validated the adverse influence of MK, CK and age≥60 years in cytogenetically unfavorable AML patients. Our proposed scoring model may be adapted in clinical practice to further the stratification of this high-risk population. [Copyright &y& Elsevier]

Monosomal karyotype (MK) has recently been reported to identify a distinct subset of acute myeloid leukemia (AML) with adverse prognosis. We retrospectively evaluated the frequency of MK in a large cohort of 549 unselected AML cases diagnosed in our department over a period of 13 years and explored potential associations with clinicobiological features and outcome. MK was found in 62 of 549 cases (11.3%), with all but one assigned to the unfavorable cytogenetic risk category; 57 of these 62 MK cases had a complex karyotype. Comparison with a subgroup of AML cases, who had unfavorable karyotypic profiles yet without MK (non-MK) and who were treated uniformly with similar, “3+7”-based regimens, revealed significant (P < 0.05) associations between MK and advanced age, low white blood cell count at diagnosis, and inferior overall survival (6.5 vs. 15 months for non-MK cases). In conclusion, MK defines a sizeable subset of patients with unfavorable cytogenetics who exhibit a distinct clinical profile, even in direct comparison with other unfavorable karyotypes. [ABSTRACT FROM AUTHOR]

Objective Monosomal karyotype ( MK) is defined as the presence of two or more autosomal monosomies or a single monosomy associated with a structural abnormality. It was first described as a high-risk cytogenetic abnormality for acute myeloid leukemia and more recently in myelodysplastic syndromes ( MDS). However, allotransplant outcome in MDS with MK has not been described. Patients and Methods We retrospectively reviewed data of 79 patients with MDS who underwent allotransplant at the University of Iowa from 1990 to 2009. We recorded patients' cytogenetic data, clinical characteristics and evaluated outcome following allogeneic stem cell transplant stratified by cytogenetic classification. Results Of 79 patients, 37 (47%) had unfavorable karyotypes (23 complex karyotype, 25 abnormal chromosome 7). Twenty-four patients (30%) had MK. Twenty-four patients (30%) relapsed and 59 (74.7%) died during study period. Patients with MK had higher 2-yr relapse incidence ( RI) (51% vs. 29%; P = 0.01), lower 2-yr event-free survival ( EFS) (8% vs. 40%; P = 0.02), and lower 2-yr overall survival ( OS)(6% vs. 41%; P = 0.02) than patients without MK. We further analyzed the effect of MK in each unfavorable karyotype composite. Although the outcome was not statistically different, unfavorable karyotypes with patients with MK showed a trend toward higher 2-yr RI [hazard ratio ( HR), 1.7; P = 0.34], lower 2-yr EFS ( HR, 1.5; P = 0.29), and lower 2-yr OS ( HR, 1.5; P = 0.28) compared to unfavorable karyotypes without MK. Conclusion Cytogenetic abnormalities remain an important prognostic factor for allotransplant outcome of MDS. Our results suggested poor allotransplant outcomes with high RI and low OS in MDS with MK. [ABSTRACT FROM AUTHOR]

We studied cytogenetic risk grouping schemes to stratify patients with acute myelogenous leukemia (AML) (n = 212) into prognostically distinct subgroups for relapse incidence (RI), progression-free survival (PFS), and overall survival (OS) after allogeneic hematopoietic stem cell transplantation (HSCT). Patients were divided according to cytogenetic abnormalities based on the Medical Research Council, Southwest Oncology Group, Cancer and Leukemia Group B (CALGB), Dana-Farber, and recently described monosomal karyotype (MK) classification schemes and analyzed separately for first complete remission (CR1; n = 134) and beyond (CR2+; n = 78). Multivariate analysis was performed after adjusting for age, conditioning intensity, donor type, and cytomegalovirus serology status. Although none of the covariates was associated with OS in CR1, the presence of MK (MK+) was associated with worse RI and PFS (hazard ratio [HR], 3.3, P = .01 and HR, 2.0, P = .05, respectively). No other classification scheme was predictive of outcomes in CR1. In CR2+, for RI, only MK+ was predictive of poor outcome (HR, 3.7; P = .03). For PFS, all 5 classification schemes were predictive, and for OS, both the MK+ and CALGB adverse karyotypes were predictive. In addition to cytogenetics, nonmyeloablative conditioning was associated with decreased PFS and OS in patients in CR2+ in all models. Our results indicate that among all classification schemes, MK classification can identify a subgroup with very poor prognosis in patients with AML after allogeneic HSCT. [Copyright &y& Elsevier]

Monosomal karyotype (MK) refers to the presence of two or more distinct autosomal monosomies or a single monosomy associated with a structural abnormality. In acute myeloid leukemia, MK has been shown to be prognostically worse than an otherwise complex karyotype. The current study examines whether the same holds true for myelodysplastic syndromes (MDS). A total of 127 MDS patients (median age 70 years) with a complex karyotype were considered; 106 (83%) met the above-stipulated criteria for MK and 21 (17%) had a complex karyotype without monosomies. Survival was significantly inferior in patients with MK compared with those with a complex karyotype without monosomies (P=0.01; HR 1.9, 95% confidence interval (95% CI), 1.1-3.3). Multivariable analysis identified MK (P=0.002), advanced age (P=0.0004) and bone marrow blast percentage (0.04) as independent risk factors for survival. There was no difference in survival among MK patients further substratified by the presence or absence of monosomy 7 and/or monosomy 5. Although not statistically significant, leukemia-free survival was also worse with MK compared with complex karyotype without monosomies (P=0.09; HR 2.7, 95% CI 0.8-9.0). MK in MDS identifies a prognostically worse subgroup of patients with a complex karyotype, regardless of whether monosomy 7 or 5 is part of the MK component. [ABSTRACT FROM AUTHOR]