CD34 expression and the outcome of nucleophosmin 1-mutated acute myeloid leukemia.

CD34 positivity has been considered as an adverse prognostic factor in acute myeloid leukemia (AML). Although nucleophosmin 1-mutated (NPM1m) AML is usually CD34 negative, this marker may be expressed at diagnosis or acquired at relapse in a variable number of cases. Our objective was to ascertain if CD34 expression has any influence on the general outcome of this form of acute leukemia. Analysis of clinical outcome (complete remissions, relapses, disease-free survival, and overall survival) was performed depending on the degree of expression of CD34 determined by flow cytometry, in 67 adult patients with NPM1m AML. CD34 expression did not have any influence on the variables analyzed whatever the percentage of blasts expressing this marker. In contrast to other forms of AML, CD34 expression is not an unfavorable prognostic factor in NPM1m AML, neither at diagnosis nor at relapse.

Prognostic significance of copy number alterations in adolescent and adult patients with precursor B acute lymphoblastic leukemia enrolled in PETHEMA protocols.

BACKGROUND: Some copy number alterations (CNAs) have independent prognostic significance for adults with acute lymphoblastic leukemia (ALL). METHODS: This study analyzed via multiplex ligation-dependent probe amplification the frequency and prognostic impact of CNAs of 12 genetic regions in 142 adolescents and adults with de novo precursor B-cell ALL. RESULTS: The cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletion (59 of 142 or 42%) was the most frequent CNA, and it was followed by Ikaros family zinc finger 1 (IKZF1) losses (49 of 142 or 35%). IKZF1 deletions were more prevalent in Philadelphia chromosome (Ph)-positive ALL and were associated with advanced age and high white blood cell (WBC) counts. The multivariate analysis showed that advanced age and early B-cell factor 1 (EBF1) deletions were associated with chemotherapy resistance in both the whole series (hazard ratios, 0.949 and 0.135, respectively) and the Ph-negative subgroup (hazard ratios, 0.946 and 0.118, respectively). High WBC counts and focal IKZF1 deletions correlated with disease recurrence (hazard ratios, 1.005 and 1.869, respectively), whereas advanced age and CDKN2A/B losses influenced overall survival in both the whole series (hazard ratios, 1.038 and 2.545, respectively) and the Ph-negative subgroup (hazard ratios, 1.044 and 2.105, respectively). CONCLUSIONS: Deletions of EBF1, IKZF1, and CDKN2A/B have an independent adverse prognosis for adolescents and adults with B-precursor ALL, and this suggests that these CNAs should be included in the initial risk assessment of ALL.

A thirty-five nucleotides BCR-ABL1 insertion mutation of controversial significance confers resistance to imatinib in a patient with chronic myeloid leukemia (CML).

Tyrosine kinase inhibitors (TKI) have improved the management of patients with chronic myeloid leukemia (CML). However, a significant proportion of patients does not achieve the optimal response or are resistant to TKI. ABL1 kinase domain mutations have been extensively implicated in the pathogenesis of TKI resistance. Although deletion or insertion of nucleotides in BCR-ABL1 has rarely been described, we identified a CML patient with an already described 35 nucleotides insertion (BCR-ABL1(35INS)) of controversial significance, that confers resistance to imatinib but sensitivity to dasatinib.

Mobilization and engraftment of peripheral blood stem cells in healthy related donors >55 years old.

BACKGROUND AIMS: The increasing scarcity of young related donors has led to the use of older donors for related allogeneic hematopoietic stem cell transplantation (HSCT). This study analyzed the influence of age on the results of mobilization of peripheral blood stem cells (PBSCs) in healthy donors as well as on the engraftment and outcome of HSCT. METHODS: A retrospective analysis from a single center was performed comparing the results of PBSC mobilization from related healthy donors according to their age. RESULTS: The study included 133 consecutive related donors. The median age was 50 years (range, 4-77 years); 70 (53%) donors were males, and 44 (33%) were >55 years old. All donors were mobilized with granulocyte colony-stimulating factor for 5 days. The peak CD34(+) cell count in peripheral blood was higher in younger than in older donors (median, 90.5 CD34(+) cells/µL [range, 18-240 CD34(+) cells/µL] versus 72 CD34(+) cells/µL [range, 20-172.5 CD34(+) cells/µL], P = 0.008). The volume processed was lower in younger than in older donors (16,131 mL [range, 4424-36,906 mL] versus 18,653 mL [range, 10,003-26,261 mL], P = 0.002) with similar CD34(+) cells collected (579.3 × 10(6) cells [range, 135.14 × 10(6)-1557.24 × 10(6) cells] versus 513.69 × 10(6) cells [range, 149.81 × 10(6)-1290 × 10(6) cells], P = 0.844). There were no differences in time to recovery of neutrophils and platelets or in the incidences of acute and chronic graft-versus-host disease, overall survival, non-relapse mortality and relapse incidence. CONCLUSIONS: Donors >55 years old mobilized fewer CD34(+) cells and required a greater volume to collect a similar number of CD34(+) cells. The outcome of HSCT was not influenced by donor age. Donor age should not be a limitation for related allogeneic HSCT.

Correlation of CD11b and CD56 expression in adult acute myeloid leukemia with cytogenetic risk groups and prognosis.

Among other phenotypic markers, CD11b expression has been considered as an unfavorable prognostic factor, both in terms of overall survival (OS), disease-free survival (DFS), and attainment and duration of complete remissions (CRs) in adult patients with acute myeloid leukemia (AML). Recently, some groups have restricted its prognostic impact to poor prognostic karyotypic risk groups. The aim of this study was to retrospectively analyze the prevalence of CD11b and of CD56 expression in blast cells of 158 AML patients [excluding those with t(15;17)] stratified according to their cytogenetic risk and to correlate these phenotypic characteristics with OS, DFS, and CR. CD11b was more frequently expressed in intermediate and unfavorable cytogenetic prognostic groups (38.9 and 35.5 %, respectively) than in the favorable group (9.5 %). No differences were observed in CD56 expression according to the cytogenetic risk groups. When OS, DFS, and CR were analyzed according to these two markers, no statistical differences were recorded in any cytogenetic risk group. In conclusion, although CD11b was more frequently expressed in blast cells of patients with intermediate and unfavorable cytogenetic risk groups, this feature did not translate into different clinical outcome. Similarly, CD56 positivity did not have any influence on the prognosis of these patients.

Multilineage dysplasia is associated with a poorer prognosis in patients with de novo acute myeloid leukemia with intermediate-risk cytogenetics and wild-type NPM1.

Acute myeloid leukemia (AML) with myelodysplasia-related changes is characterized by the presence of multilineage dysplasia (MLD), frequently related to high-risk cytogenetics and poor outcome. However, the presence of MLD does not modify the favorable prognostic impact of NPM1 mutation. The prognosis of patients with AML presenting marked dysplasia lacking high-risk cytogenetics and NPM1 mutation is uncertain. We evaluated the prognostic impact of MLD in 177 patients with intermediate-risk cytogenetics AML (IR-AML) and wild-type NPM1. Patients were categorized as MLD-WHO (WHO myelodysplasia criteria; n = 43, 24 %), MLD-NRW (significant MLD non-reaching WHO criteria; n = 16, 9 %), absent MLD (n = 80, 45 %), or non-evaluable MLD (n = 38, 22 %). No differences concerning the main characteristics were observed between patients with or without MLD. Outcome of patients with MLD-WHO and MLD-NRW was similar, and significantly worse than patients lacking MLD. The presence of MLD (66 vs. 80 %, p = 0.03; HR, 95 % CI = 2.3, 1.08-4.08) and higher leukocyte count at diagnosis was the only variable associated with lower probability of complete remission after frontline therapy. Concerning survival, age and leukocytes showed an independent prognostic value, whereas MLD showed a trend to a negative impact (p = 0.087, HR, 95 % CI = 1.426, 0.95-2.142). Moreover, after excluding patients receiving an allogeneic stem cell transplantation in first CR, MLD was associated with a shorter survival (HR, 95 % CI = 1.599, 1.026-2.492; p = 0.038). In conclusion, MLD identifies a subgroup of patients with poorer outcome among patients with IR-AML and wild-type NPM1.

Cytogenetic aberrations and their prognostic value in a series of 330 splenic marginal zone B-cell lymphomas: a multicenter study of the Splenic B-Cell Lymphoma Group.

We conducted a retrospective collaborative study to cytogenetically characterize splenic marginal zone lymphoma (SMZL) and ascertain the prognostic value of chromosomal aberrations. Of 330 cases, 72% displayed an aberrant karyotype, 53% were complex, and 29% had a single aberration. The predominant aberrations were gains of 3/3q and 12q, deletions of 7q and 6q and translocations involving 8q/1q/14q. CD5 expression was detected in 39 of 158 cases (25%). The cytogenetic makeup of the CD5(+) group differed significantly from that of the CD5(-) group. Cases with unmutated IGHV were significantly associated with deletions of 7q and TP53. A strong association was noted between usage of the IGVH1-2 and deletion 7q, 14q alterations, and abnormal karyotype. On univariate analysis, patients with more than or equal to 2 aberrations, 14q alterations, and TP53 deletions had the shortest survival; 7q deletion did not affect survival. On multivariate analysis, cytogenetic aberrations did not retain prognostic significance; the parameters negatively affecting survival were hemoglobin and age. In conclusion, the cytogenetic profile of SMZL is distinct from other B-cell lymphomas. Complexity of the karyotype, 14q aberrations, and TP53 deletions are poor prognostic indicators and may be considered together with other clinicobiologic parameters to ascertain the prognosis of SMZL.

Predictive factors for poor peripheral blood stem cell mobilization and peak CD34(+) cell count to guide pre-emptive or immediate rescue mobilization.

BACKGROUND AIMS: Failure in mobilization of peripheral blood (PB) stem cells is a frequent reason for not performing hematopoietic stem cell transplantation (HSCT). Early identification of poor mobilizers could avoid repeated attempts at mobilization, with the administration of pre-emptive rescue mobilization. METHODS: Data from the first mobilization schedule of 397 patients referred consecutively for autologous HSCT between 2000 and 2010 were collected. Poor mobilization was defined as the collection of < 2 × 10(6) CD34(+)cells/kg body weight (BW). RESULTS: The median age was 53 years (range 4-70) and 228 (57%) were males. Diagnoses were multiple myeloma in 133 cases, non-Hodgkin's lymphoma in 114, acute myeloid leukemia or myelodysplastic syndrome in 81, Hodgkin's lymphoma in 42, solid tumors in 17 and acute lymphoblastic leukemia in 10. The mobilization regimen consisted of recombinant human granulocyte-colony-stimulating factor (G-CSF) in 346 patients (87%) and chemotherapy followed by G-CSF (C + G-CSF) in 51 (13%). Poor mobilization occurred in 105 patients (29%), without differences according to mobilization schedule. Diagnosis, previous therapy with purine analogs and three or more previous chemotherapy lines were predictive factors for poor mobilization. A CD34(+)cell count in PB > 13.8/µL was enough to ensure ≥ 2 × 10(6) CD34(+)cells/kg, with high sensitivity (90%) and specificity (91%). CONCLUSIONS: The prevalence of poor mobilization was high, being associated with disease type, therapy with purine analogs and multiple chemotherapy regimens. The threshold of CD34(+) cell count in PB identified poor mobilizers, in whom the administration of immediate or pre-emptive plerixafor could be useful to avoid a second mobilization.

Incidence and prognostic impact of secondary cytogenetic aberrations in a series of 145 patients with mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a mature B-cell neoplasm with an aggressive behavior, characterized by the t(11;14)(q13;q32). Several secondary genetic abnormalities with a potential role in the oncogenic process have been described. Studies of large MCL series using conventional cytogenetics, and correlating with proliferation and survival, are scarce. We selected 145 MCL cases at diagnosis, displaying an aberrant karyotype, from centers belonging to the Spanish Cooperative Group for Hematological Cytogenetics. Histological subtype, proliferative index and survival data were ascertained. Combined cytogenetic and molecular analyses detected CCND1 translocations in all cases, mostly t(11;14)(q13;q32). Secondary aberrations were present in 58% of patients, the most frequent being deletions of 1p, 13q and 17p, 10p alterations and 3q gains. The most recurrent breakpoints were identified at 1p31-32, 1p21-22, 17p13, and 1p36. Aggressive blastoid/pleomorphic variants displayed a higher karyotypic complexity, a higher frequency of 1p and 17p deletions and 10p alterations, a higher proliferation index and poor survival. Gains of 3q and 13q and 17p13 losses were associated with reduced survival times. Interestingly, gains of 3q and 17p losses added prognostic significance to the morphology in a multivariate analysis. Our findings confirm previous observations indicating that proliferation index, morphology and several secondary genetic alterations (3q gains and 13q and 17p losses) have prognostic value in patients with MCL. Additionally, we observed that 3q gains and 17p losses detected by conventional cytogenetics are proliferation-independent prognostic markers indicating poor outcome.

New chromosomal alterations in a series of 23 splenic marginal zone lymphoma patients revealed by Spectral Karyotyping (SKY).

Splenic marginal zone lymphoma (SMZL) is a B-cell lymphoproliferative disorder with characteristic clinical, immunophenotypic, cytological and histological features. Some karyotypic abnormalities have been related to this disorder and most of them are usually complex and difficult to define. The aim of present study was to characterize new chromosomal aberrations involved in this disease. We performed conventional banding cytogenetics and Spectral Karyotyping (SKY) technique in 23 patients diagnosed with SMZL having a complex karyotype among a series of 160 SMZL cases. Del(7)(q22-q32) and trisomy 3/3q were the most common chromosomal aberrations. In addition, new translocations involving chromosomes 3, 6, 8, 9, 12 and 14q32 region were detected.

Memory B cell dysregulation in HIV-1-infected individuals.

OBJECTIVE: To characterize the effect of the HIV-1 infection and antiretroviral treatment (ART) in the human memory B (MEB)-cell compartment. DESIGN: A cross-sectional study was designed to analyze MEB cells of HIV-1 ART treated and ART-naive study participants, and uninfected individuals. METHODS: Frequency and absolute counts of MEB cell subsets in blood were determined by multicolor flow cytometry. Spontaneous cell death and B-cell proliferative capacity was evaluated in vitro by cell culture and flow cytometry. Splenic function was determined by pitted erythrocytes quantification in HIV-1 ART-treated study participants. RESULTS: HIV-1 ART-treated individuals did not show functional hyposplenism despite the lack of recovery IgMIgDCD27 marginal zone-like B cells. Moreover, two germinal center-dependent MEB cells subsets were also dysregulated in HIV-1 individuals: IgMIgDCD27 (IgM only) cells were increased, whereas the switched subset (IgMIgD) was reduced in viremic individuals. Althought ART restored the numbers of these populations; the switched MEB cells were enriched in CD27 cells, which showed the highest susceptibility to spontaneous cell death ex vivo. In addition, B cells from viremic individuals showed a poor response to B-cell receptor and toll-like receptor 9 stimulation that was circumvented when both stimuli were used simultaneously. CONCLUSION: B cells from HIV-1 study participants show a poor stimulation capacity, that may be bypassed by the proper combination of stimuli, and a dysregulated MEB cell pool that suggest an affectation of the germinal center reaction, only partially normalized by ART. Interestingly, hyposplenism does not explain the lack of recovery of the marginal zone-like B cells in ART-treated HIV-1 individuals.

Advanced stage is the most important prognostic factor for survival in patients with systemic acquired immunodeficiency syndrome-related non-Hodgkin's Lymphoma treated with CHOP and highly active antiretroviral therapy.

In the era of highly active antiretroviral therapy (HAART), the prognosis for acquired immunodeficiency syndrome-related lymphomas (ARL) seems to be similar to that for aggressive B-cell lymphomas in human immunodeficiency virus (HIV)-negative patients. This improvement in prognosis might lead to a modification of the classic prognostic factors for ARL. We evaluated the prognostic factors for response and survival in a series of HIV-infected patients with systemic non-Hodgkin's lymphoma (NHL) in the HAART era. Forty patients with systemic NHL treated with a CHOP-based chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone) and HAART were studied. The main clinicopathologic and laboratory parameters were recorded in each case. Patients were scheduled to receive cycles of CHOP therapy, and all received granulocyte colony-stimulating factor. In addition, 9 patients received rituximab (375 mg/m2). The complete remission (CR) rate was 62.5% (n = 25). No prognostic factors influencing CR attainment were found. The 5-year disease-free survival (DFS) probability (95% confidence interval [CI]) was 73% (54%-92%). The median overall survival (OS) time was 69.17 months, and the 5-year OS rate (95% CI) was 51% (35%-67%). A disease stage of III to IV was the only parameter with prognostic influence on DFS. The factors influencing OS were an International Prognostic Index >2, an Eastern Cooperative Ecology Group (ECOG) score >2, and a disease stage of III to IV. Patients with an advanced stage had a lower OS probability in a multivariate analysis (odds ratio, 4.24; 95% CI, 1.24- 14.57). Advanced stage was the main prognostic factor predicting survival in ARL treated with CHOP and HAART.

[Osteoporosis as a first manifestation of systemic mastocytosis. Study of 6 cases]. / Osteoporosis como primera manifestación de una mastocitosis sistémica. Estudio de 6 casos.

BACKGROUND AND OBJECTIVE: We describe 6 cases of secondary osteoporosis due to systemic mastocytosis diagnosed in the last 6 years. RESULTS: Three females and 3 males, age range: 47-66 years, diagnosed with osteoporosis were subsequently diagnosed with systemic mastocytosis. Diagnosis delay: 0.5-17 years. Cutaneous involvement was present in 3 patients, hematologic involvement in 2 patients and gastrointestinal involvement in 2 patients. Histamine levels in urine were elevated in all cases. Four patients had fractures. Treatment with bisphosphonates was started. After 3 years the values of bone mineral density (BMD) improved in the 5 patients evaluated. Two patients had new vertebral fractures and started teriparatide. CONCLUSIONS: Osteoporosis is an unfrequent initial manifestation of systemic mastocytosis. These patients have a high risk of fractures. Our results suggest that although bisphosphonates improve the bone mineral density the risk of fractures persists.

[Evaluation of splenic function by dynamic gammagraphy, study of pitted erythrocytes and submembranous vacuoles in patients with slight and severe splenic trauma receiving conservative treatment or splenectomy]. / Valoración de la función esplénica mediante gammagrafía dinámica y estudio de "pits" de la membrana eritrocitaria y de vacuolas submembranarias en los pacientes con traumatismo leve y grave de bazo tratados de forma conservadora o mediante esplenectomía.

BACKGROUND AND OBJECTIVE: The splenic function of patients followed by the Department of General and Digestive Surgery in the Hospital Universitari Germans Trias i Pujol (HUGTiP) from 1985 to 2003 for different degrees of splenic trauma according to the classification of the American Association for the Surgery of Trauma (AAST) 1994 was quantified and related to the treatment received (non surgical, total splenectomy with or without splenosis and splenectomy plus autotransplantation) to detect splenic dysfunction predisposing the development of postsplenectomy sepsis (PSS). PATIENTS AND METHOD: 43 patients underwent an isotopic study with dynamic splenic gammagraphy and pitted erythrocytes (Normarsky optics) and submembranous vacuoles (transmission electron microscopy) were evaluated. RESULTS: The non surgical group presented normal phagocytic and filtration function with the median speed of splenic enhancement being 3.46 Kcts/s2 (interval: 0.8-6.98). The percentage of pitted erythrocytes was 2% (0-8.8), the number of pits per erythrocyte was 0.03 (0-0.12) and the percentage of erythrocytes with 1, 2, 3 and 4 pits was 1.6%, 0.4%, 0% and 0%, respectively. The percentage of red cells with submembranous vacuoles was 2.55% (0-5.6), the number of vacuoles per red cell was 0.03 (0-0.06) and the percentage of red cells with 1, 2, 3 and 4 vacuoles was 2%, 0.2%, 0% and 0%, respectively. In the operated group, the splenic enhancement speed was 0.08 Kcts/s2 (0-1.75) (p < 0.0001). The percentage of pitted erythrocytes was 38% (0.2-64) (p < 0.0001), the number of pits per erythrocyte was 0.86 (0-1.8) (p < 0.0001) and the percentage of erythrocytes with 1,2,3 and 4 pits was 16.39%, 7.2%, 3.59% and 2.52%, respectively (p < 0.0001). The percentage of red cells with submembranous vacuoles was 11.2% (1.8-31.9) (p = 0.0006); the number of vacuoles per cell was 0.16 (p = 0.0022) and the percentage of red cells with 1, 2, 3 and 4 vacuoles was 6.51%, 1.73%, 0.4% and 0.2%, respectively (p = 0.0246, 0.0010, < 0.0001 and 0.0002, respectively). CONCLUSIONS: Splenic function of patients with a history of splenic trauma receiving conservative treatment is normal, independently of the degree of the lesion, thereby reinforcing the use of this therapeutic approach to avoid the development of postsplenectomy sepsis. In the patients treated with splenectomy, with or without splenosis, splenic function was absent or very altered being partially conserved in cases treated with splenectomy plus autotransplantation.

Usefulness of bronchoalveolar lavage and flow cytometry in patients with hematological malignancies and respiratory failure. / Utilidad del lavado broncoalveolar y la citometría de flujo en pacientes con hemopatías malignas e insuficiencia respiratoria.

BACKGROUND AND OBJECTIVES: Strategies to improve the efficiency of bronchoalveolar lavage (BAL) are needed. We conducted a study to establish the diagnostic value of BAL in patients with hematological malignancies and pulmonary infiltrates. PATIENTS AND METHODS: The correlation of cytologic and flow cytometric study of BAL with the microbiological findings and the clinical evolution was determined. RESULTS: Seventy BAL were performed and flow cytometric study was analyzed in 23 of them. Fifty-three patients did not present any adverse event attributable to BAL. Anti-infectious therapy was modified in 64 (91%) patients. T lymphocyte count >0.3×109/l in peripheral blood was associated with longer OS at 3 years (53 vs. 22%, p=.009). Higher CD4 (>20/µL) and CD8 (>35/µL) lymphocyte counts in the BAL were associated with a longer OS at 3 years: 82 vs. 21% (p=.030) and 80 vs. 23% (p=.059). CONCLUSIONS: Our study confirms the clinical value of BAL for treatment decision making in patients with hematological malignancies and acute respiratory failure.

Relapse risk after autologous stem cell transplantation in patients with lymphoma based on CD34+ cell dose.

It is unclear whether higher CD34 + cell doses infused for ASCT have any influence on survival or relapse in patients with lymphoma. We analyzed the correlation of infused CD34 + cell dose with relapse, survival, and hematopoietic recovery in 146 consecutive patients undergoing ASCT for lymphoma. Higher doses (>5 × 106/kg) were significantly correlated with earlier hematopoietic recovery, fewer infectious episodes, lower transfusion needs. No differences were observed in lymphoma outcomes (4-year relapse incidence of 38% [95%CI: 29%-48%] in the lower dose group versus 51% [95%CI: 30%-69%] in the higher dose group, 10-year OS probabilities of 58% [95%CI: 48%-68%] versus 75% [95%CI: 59%-91%], 10-year DFS probabilities of 47% [95%CI: 37%-57%] versus 42% [95%CI: 23%-61%], p = NS for all outcomes). In this series, a higher infused CD34 + cell dose did not correlate with survival or relapse but correlated with earlier hematopoietic recovery and lower resource consumption.

Targeted deep sequencing improves outcome stratification in chronic myelomonocytic leukemia with low risk cytogenetic features.

Clonal cytogenetic abnormalities are found in 20-30% of patients with chronic myelomonocytic leukemia (CMML), while gene mutations are present in >90% of cases. Patients with low risk cytogenetic features account for 80% of CMML cases and often fall into the low risk categories of CMML prognostic scoring systems, but the outcome differs considerably among them. We performed targeted deep sequencing of 83 myeloid-related genes in 56 CMML patients with low risk cytogenetic features or uninformative conventional cytogenetics (CC) at diagnosis, with the aim to identify the genetic characteristics of patients with a more aggressive disease. Targeted sequencing was also performed in a subset of these patients at time of acute myeloid leukemia (AML) transformation. Overall, 98% of patients harbored at least one mutation. Mutations in cell signaling genes were acquired at time of AML progression. Mutations in ASXL1, EZH2 and NRAS correlated with higher risk features and shorter overall survival (OS) and progression free survival (PFS). Patients with SRSF2 mutations associated with poorer OS, while absence of TET2 mutations (TET2wt) was predictive of shorter PFS. A decrease in OS and PFS was observed as the number of adverse risk gene mutations (ASXL1, EZH2, NRAS and SRSF2) increased. On multivariate analyses, CMML-specific scoring system (CPSS) and presence of adverse risk gene mutations remained significant for OS, while CPSS and TET2wt were predictive of PFS. These results confirm that mutation analysis can add prognostic value to patients with CMML and low risk cytogenetic features or uninformative CC.

Identification of novel cytogenetic markers with prognostic significance in a series of 968 patients with primary myelodysplastic syndromes.

BACKGROUND AND OBJECTIVES: The main prognostic factors in myelodysplastic syndromes (MDS) are chromosomal abnormalities, the proportion of blasts in bone marrow and number and degree of cytopenias. A consensus-defined International Prognostic Scoring System (IPSS) for predicting outcome and planning therapy in MDS has been developed, but its prognostic value in a large and independent series remains unproven. Furthermore, the intermediate-risk cytogenetic subgroup defined by the IPSS includes a miscellaneous number of different single abnormalities of uncertain prognostic significance at present. The main aim of the present study was to identify chromosomal abnormalities with a previously unrecognized good or poor prognosis in order to find new cytogenetic markers with predictive value. DESIGN AND METHODS: We report the cytogenetic findings in a series of 968 patients with primary MDS from the Spanish Cytogenetics Working Group, Grupo Cooperativo Español de Citogenética Hematológica (GCECGH). RESULTS: In this series of 968 MDS patients, we found various cytogenetic aberrations with a new prognostic impact. Complex karyotype, -7/7q- and i(17q) had a poor prognosis; normal karyotype, loss of Y chromosome, deletion 11q, deletion 12p and deletion 20q as single alterations had a good prognosis. Intermediate prognosis aberrations were rearrangements of 3q21q26, trisomy 8, trisomy 9, translocations of 11q and del(17p). Finally, a new group of single or double cytogenetic abnormalities, most of which are considered rare cytogenetic events and are usually included in the intermediate category of the IPSS, showed a trend to poor prognosis. INTERPRETATION AND CONCLUSIONS: This study suggests that some specific chromosomal abnormalities could be segregated from the IPSS intermediate-risk cytogenetic prognostic subgroup and included in the low risk or in the poor risk groups.