Differing clinical features between Japanese and Caucasian patients with myelodysplastic syndromes: Analysis from the International Working Group for Prognosis of MDS.

Clinical features of myelodysplastic syndromes (MDS) could be influenced by many factors, such as disease intrinsic factors (e.g., morphologic, cytogenetic, molecular), extrinsic factors (e.g, management, environment), and ethnicity. Several previous studies have suggested such differences between Asian and European/USA countries. In this study, to elucidate potential differences in primary untreated MDS between Japanese (JPN) and Caucasians (CAUC), we analyzed the data from a large international database collected by the International Working Group for Prognosis of MDS (300 and 5838 patients, respectively). JPN MDS were significantly younger with more severe cytopenias, and cytogenetic differences: less del(5q) and more +1/+1q, -1/del(1p), der(1;7), -9/del(9q), del(16q), and del(20q). Although differences in time to acute myeloid leukemia transformation did not occur, a significantly better survival in JPN was demonstrated, even after the adjustment for age and FAB subtypes, especially in lower, but not in higher prognostic risk categories. Certain clinical factors (cytopenias, blast percentage, cytogenetic risk) had different impact on survival and time to transformation to leukemia between the two groups. Although possible confounding events (e.g., environment, diet, and access to care) could not be excluded, our results indicated the existence of clinically relevant ethnic differences regarding survival in MDS between JPN and CAUC patients. The good performance of the IPSS-R in both CAUC and JP patients underlines that its common risk model is adequate for CAUC and JP.

Cytomorphology review of 100 newly diagnosed lower-risk MDS patients in the European LeukemiaNet MDS (EUMDS) registry reveals a high inter-observer concordance.

The European LeukemiaNet MDS (EUMDS) registry is collecting data of myelodysplastic syndrome (MDS) patients belonging to the IPSS low or intermediate-1 category, newly diagnosed by local cytologists. The diagnosis of MDS can be challenging, and some data report inter-observer variability with regard to the assessment of the MDS subtype. In order to ensure that correct diagnoses were made by the participating centres, blood and bone marrow slides of 10% of the first 1000 patients were reviewed by an 11-person panel of cytomorphologists. All slides were rated by at least 3 panel members (median 8 panel members; range 3-9). Marrow slides from 98 out of 105 patients were of good quality and therefore could be rated properly according to the WHO 2001 classification, including assessment of dysplastic lineages. The agreement between the reviewers whether the diagnosis was MDS or non-MDS was strong with an intra-class correlation coefficient (ICC) of 0.85. Six cases were detected not to fit the entry criteria of the registry, because they were diagnosed uniformly as CMML or AML by the panel members. The agreement by WHO 2001 classification was strong as well (ICC = 0.83). The concordance of the assessment of dysplastic lineages was substantial for megakaryopoiesis and myelopoiesis and moderate for erythropoiesis. Our data show that in general, the inter-observer agreement was high and a very low percentage of misdiagnosed cases had been entered into the EUMDS registry. Further studies including histomorphology are warranted.

Time-dependent changes in mortality and transformation risk in MDS.

In myelodysplastic syndromes (MDSs), the evolution of risk for disease progression or death has not been systematically investigated despite being crucial for correct interpretation of prognostic risk scores. In a multicenter retrospective study, we described changes in risk over time, the consequences for basal prognostic scores, and their potential clinical implications. Major MDS prognostic risk scoring systems and their constituent individual predictors were analyzed in 7212 primary untreated MDS patients from the International Working Group for Prognosis in MDS database. Changes in risk of mortality and of leukemic transformation over time from diagnosis were described. Hazards regarding mortality and acute myeloid leukemia transformation diminished over time from diagnosis in higher-risk MDS patients, whereas they remained stable in lower-risk patients. After approximately 3.5 years, hazards in the separate risk groups became similar and were essentially equivalent after 5 years. This fact led to loss of prognostic power of different scoring systems considered, which was more pronounced for survival. Inclusion of age resulted in increased initial prognostic power for survival and less attenuation in hazards. If needed for practicability in clinical management, the differing development of risks suggested a reasonable division into lower- and higher-risk MDS based on the IPSS-R at a cutoff of 3.5 points. Our data regarding time-dependent performance of prognostic scores reflect the disparate change of risks in MDS subpopulations. Lower-risk patients at diagnosis remain lower risk whereas initially high-risk patients demonstrate decreasing risk over time. This change of risk should be considered in clinical decision making.

Prognostic impact of chromosomal translocations in myelodysplastic syndromes and chronic myelomonocytic leukemia patients. A study by the spanish group of myelodysplastic syndromes.

Chromosomal translocations are rare in the myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). With the exception of t(3q), translocations are not explicitly considered in the cytogenetic classification of the IPSS-R and their impact on disease progression and patient survival is unknown. The present study was aimed at determining the prognostic impact of translocations in the context of the cytogenetic classification of the IPSS-R. We evaluated 1,653 patients from the Spanish Registry of MDS diagnosed with MDS or CMML and an abnormal karyotype by conventional cytogenetic analysis. Translocations were identified in 168 patients (T group). Compared with the 1,485 patients with abnormal karyotype without translocations (non-T group), the T group had a larger proportion of patients with refractory anemia with excess of blasts and higher scores in both the cytogenetic and global IPSS-R. Translocations were associated with a significantly shorter survival and higher incidence of transformation into AML at univariate analysis but both features disappeared after multivariate adjustment for the IPSS-R cytogenetic category. Patients with single or double translocations other than t(3q) had an outcome similar to those in the non-T group in the intermediate cytogenetic risk category of the IPSS-R. In conclusion, the presence of translocations identifies a subgroup of MDS/CMML patients with a more aggressive clinical presentation that can be explained by a higher incidence of complex karyotypes. Single or double translocations other than t(3q) should be explicitly considered into the intermediate risk category of cytogenetic IPSS-R classification.

Use of newer prognostic indices for patients with myelodysplastic syndromes in the low and intermediate-1 risk categories: a population-based study.

BACKGROUND: We aimed to compare the ability of recently developed prognostic indices for myelodysplastic syndromes to identify patients with poor prognoses within the lower-risk (low and intermediate-1) categories defined by the International Prognosis Scoring System (IPSS). METHODS: We included patients with de-novo myelodysplastic syndromes diagnosed between Nov 29, 1972, and Dec 15, 2011, who had low or intermediate-1 IPSS scores and were in the Spanish Registry of Myelodysplastic Syndromes. We reclassified these patients with the new prognostic indices (revised IPSS [IPSS-R], revised WHO-based Prognostic Scoring System [WPSS-R], Lower Risk Scoring System [LRSS], and the Grupo Español de Síndromes Mielodisplásicos [Spanish Group of Myelodysplastic Syndromes; GESMD]) and calculated the overall survival of the different risk groups within each prognostic index to identify the groups of patients with overall poor prognoses (defined as an expected overall survival <30 months). We calculated overall survival with the Kaplan-Meier method. FINDINGS: We identified 2373 patients. None of the prognostic indices could be used to identify a population with poor prognoses (median overall survival <30 months) for the patients with low IPSS scores (1290 individuals). In the group with intermediate-1 scores (1083 individuals), between 17% and 47% of patients were identified as having poor prognoses with the new prognostic indices. The LRSS had the best model fit with the lowest value in the Akaike information criteria test, whereas the IPSS-R identified the largest proportion of patients with poor prognoses (47%). Patients with intermediate-1 scores who were classified as having poor prognoses by one or more prognostic index (646 [60%] individuals) had worse median overall survival (33·1 months, 95% CI 28·4-37·9) than did patients who were classified as having low risk by all prognostic indices (63·7 months, 49·5-78·0], HR 1·9, 95% CI 1·6-2·3, p<0·0001) INTERPRETATION: Recently proposed prognostic indices for myelodysplastic syndromes can be used to improve identification of patients with poor prognoses in the group of patients with intermediate-1 IPSS scores, who could potentially benefit from a high-risk treatment approach. FUNDING: None.

Fluorescence in situ hybridization of TP53 for the detection of chromosome 17 abnormalities in myelodysplastic syndromes.

Conventional G-banding cytogenetics (CC) detects chromosome 17 (chr17) abnormalities in 2% of patients with de novo myelodysplastic syndromes (MDS). We used CC and fluorescence in situ hybridization (FISH) (LSI p53/17p13.1) to assess deletion of 17p in 531 patients with de novo MDS from the Spanish Group of Hematological Cytogenetics. FISH detected - 17 or 17p abnormalities in 13 cases (2.6%) in whom no 17p abnormalities were revealed by CC: 0.9% of patients with a normal karyotype, 0% in non-informative cytogenetics, 50% of patients with a chr17 abnormality without loss of 17p and 4.7% of cases with an abnormal karyotype not involving chr17. Our results suggest that applying FISH of 17p13 to identify the number of copies of the TP53 gene could be beneficial in patients with a complex karyotype. We recommend using FISH of 17p13 in young patients with a normal karyotype or non-informative cytogenetics, and always in isolated del(17p).

Acute myeloid leukemia with inv(3)(q21q26.2) or t(3;3)(q21;q26.2): Clinical and biological features and comparison with other acute myeloid leukemias with cytogenetic aberrations involving long arm of chromosome 3.

OBJECTIVES: To compare, from a biological and clinical perspective, a significant group of patients with AML with inv(3)(q21q26.2) or t(3;3)(q21;q26.2) with another group of AML carrying different abnormalities of 3q at q21 or q26, the latter named as the AML abn(3q) group. METHODS: We developed a national survey with the participation of 13 Spanish hospitals, and retrospectively reviewed (from 1990 to 2010) these subtypes of AML. Fifty-five patients were collected: 35 with AML inv(3)/t(3;3) and 20 with AML abn(3q). A data collecting page that included main features at diagnosis, therapeutic approach and response, and survival variables, was distributed and completed. RESULTS: We did not find significant differences in sex, age, history of myelodysplastic syndrome or chemo-/radiotherapy, clinical presentation, WBC and platelet counts, hemoglobin level, blasts immunophenotype, serum lactatedehydrogenase, peripheral blood and bone marrow cellular dysplasia, and bone marrow biopsy findings. Although the association with monosomy 7 was significantly more frequent in AML inv(3)/t(3;3), this did not seem to influence outcome. The lack of response to the different modalities of treatment and the aggressive course of the disease were the standard in both cohorts of patients. DISCUSSION: Although not yet recognized by the World Health Organization classification, our results are in agreement with the findings of other authors, who include both subsets of AML together in the same group of adverse prognosis. CONCLUSION: In an attempt to simplify and bound entities with similar genetic background and clinical behavior, it would be desirable to bring together both subgroups of AML in a single section.

5q- syndrome and multiple myeloma diagnosed simultaneously and successful treated with lenalidomide.

A 72-year-old woman was diagnosed with 5q- myelodysplastic syndrome in the course of an indolent multiple myeloma (MM). Bone marrow (BM) cytogenetics disclosed two unrelated clones: 46,XX,del(5)(q13q33), and [47,X,-X,der(1;21)(q10;q10),-4,-4,+5,del(5)(q13q31),+7,der(7)t(1;7)(p34.2;p22),add(8)(p23),-13,+15,der(16) t(1;16)(q23;q12.2),+19,-21,+mar1,+mar2]. The last complex karyotype belonged to malignant plasma cells. FISH and SKY techniques demonstrated different 5q deletions. EGR1 gene (on 5q31) lost in 5q- syndrome remained in 5q- plasma cells. Biclonal evolution was noted: myeloid 5q- cells added a deletion 13q and plasma cells showed monosomy 13. Patient achieved complete cytogenetic response of 5q- syndrome with low-dose of lenalidomide, and a partial remission of MM with high-dose of lenalidomide/dexamethasone combination.

Characterization and prognostic implication of 17 chromosome abnormalities in myelodysplastic syndrome.

The prognosis of chromosome 17 (chr17) abnormalities in patients with primary myelodysplastic syndrome (MDS) remains unclear. The revised International Prognostic Scoring System (IPSS-R) includes these abnormalities within the intermediate cytogenetic risk group. This study assessed the impact on overall survival (OS) and risk of acute myeloid leukemia transformation (AMLt) of chr17 abnormalities in 88 patients with primary MDS. We have compared this group with 1346 patients with primary MDS and abnormal karyotype without chr17 involved. The alterations of chr17 should be considered within group of poor prognosis. The different types of alterations of chromosome 17 behave different prognosis. The study confirms the intermediate prognostic impact of the i(17q), as stated in IPSS-R. The results of the study, however, provide valuable new information on the prognostic impact of alterations of chromosome 17 in complex karyotypes.

Reciprocal translocations in myelodysplastic syndromes and chronic myelomonocytic leukemias: review of 5,654 patients with an evaluable karyotype.

The infrequency of translocations in myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemias (CMML) makes their identification and reporting interesting for the recognition of the recurrent ones and the genes involved in these neoplasias. The aims of this study were to identify new translocations associated with MDS and CMML and to establish their frequency in a cohort of 8,016 patients from the Spanish Group of MDS database. The karyotype was evaluable in 5,654 (70%) patients. Among those, 2,014 (36%) had chromosomal abnormalities, including 213 (10%) translocations identified in 195 patients. The translocations were balanced in 183 (86%) cases and unbalanced in 30 (14%) cases. All chromosomes were found to be involved in translocations, with the single exception of the Y chromosome. The chromosomes most frequently involved were in decreasing frequency: 3, 1, 7, 2, 11, 5, 12, 6, and 17. Translocations were found in karyotypes as the unique chromosomal abnormality (33%), associated with another chromosomal abnormality (11%), as a part of a complex karyotype (17%), and as a part of a monosomal karyotype (38%). There were 155 translocations not previously described in MDS or CMML and nine of them appeared to be recurrent.

Complex, not monosomal, karyotype is the cytogenetic marker of poorest prognosis in patients with primary myelodysplastic syndrome.

PURPOSE: Complex karyotype (CK) is the poorest risk factor in patients with myelodysplastic syndrome (MDS). It has recently been reported that monosomal karyotype (MK) worsens the prognosis of patients with CK. PATIENTS AND METHODS; We analyzed 1,054 adult patients with MDS with an abnormal karyotype from the Spanish Registry of MDS. The aim of the study was to describe the incidence, characteristics, and prognosis of MK; the main end points were overall survival (OS) and leukemia-free survival. RESULTS: MK was identified in 172 patients (16%), most of whom (88%) presented with CK. Variables significantly associated with OS were age (hazard ratio [HR], 1.90; P < .001), bone marrow (BM) blast percentage (HR, 1.05; P < .001), hemoglobin level (HR, 1.71; P < .001), platelet count (HR, 1.41; P < .001), karyotype complexity (CK [three abnormalities]: HR, 1.81; P = .003; very CK [> three abnormalities]: HR, 2; P < .001), and abnormalities of chromosome 5 and/or 7 (HR, 1.89; P < .001). Variables significantly related to the risk of transformation to acute myeloid leukemia (AML) were higher BM blast percentage (HR, 1.12; P < .001) and karyotype complexity (CK: HR, 2.53; P = .002; very CK: HR, 2.77; P < .001). CONCLUSION: After accounting for karyotype complexity, MK was not associated with OS or evolution to AML. In conclusion, these results demonstrate that the prognostic value of MK in MDS is not independent and is mainly the result of its strong association with number of chromosomal abnormalities.

Rationale for the clinical application of flow cytometry in patients with myelodysplastic syndromes: position paper of an International Consortium and the European LeukemiaNet Working Group.

An international working group within the European LeukemiaNet gathered, aiming to determine the role of flow cytometry (FC) in myelodysplastic syndromes (MDS). It was agreed that FC has a substantial application in disease characterization, diagnosis and prognosis. FC may also be useful in predicting treatment responses and monitoring novel and standard therapeutic regimens. In this article the rationale is discussed that flow cytometry should be integrated as a part of diagnostic and prognostic scoring systems in MDS.

Prognostic value of trisomy 8 as a single anomaly and the influence of additional cytogenetic aberrations in primary myelodysplastic syndromes.

Trisomy 8 is the most common chromosomal gain in myelodysplastic syndromes (MDS), however, little is known about the features of MDS with isolated trisomy 8 and the influence of additional cytogenetic aberrations. We determined the characteristics and prognostic factors of 72 patients with trisomy 8 as a single anomaly and analysed also the impact of other aberrations added to trisomy 8 in another 62 patients. According to our study, MDS with isolated trisomy 8 was more frequent in men, with more than one cytopenia in most patients (62%) and having about 4% bone marrow blasts. The multivariate analysis demonstrated that platelet count and percentage bone marrow blasts had the strongest impact on overall survival (OS). The median OS for isolated trisomy 8, trisomy 8 plus one aberration (tr8 + 1), plus two (tr8 + 2) and plus three or more aberrations (tr8 + ≥3) was 34·3, 40, 23·4 and 5·8 months, respectively (P < 0·001). Trisomy 8 confers a poorer prognosis than a normal karyotype in MDS patients with ≥5% bone marrow blasts. This study supports the view that MDS with isolated trisomy 8 should be included in the intermediate cytogenetic risk group.

Revised international prognostic scoring system for myelodysplastic syndromes.

The International Prognostic Scoring System (IPSS) is an important standard for assessing prognosis of primary untreated adult patients with myelodysplastic syndromes (MDS). To refine the IPSS, MDS patient databases from international institutions were coalesced to assemble a much larger combined database (Revised-IPSS [IPSS-R], n = 7012, IPSS, n = 816) for analysis. Multiple statistically weighted clinical features were used to generate a prognostic categorization model. Bone marrow cytogenetics, marrow blast percentage, and cytopenias remained the basis of the new system. Novel components of the current analysis included: 5 rather than 3 cytogenetic prognostic subgroups with specific and new classifications of a number of less common cytogenetic subsets, splitting the low marrow blast percentage value, and depth of cytopenias. This model defined 5 rather than the 4 major prognostic categories that are present in the IPSS. Patient age, performance status, serum ferritin, and lactate dehydrogenase were significant additive features for survival but not for acute myeloid leukemia transformation. This system comprehensively integrated the numerous known clinical features into a method analyzing MDS patient prognosis more precisely than the initial IPSS. As such, this IPSS-R should prove beneficial for predicting the clinical outcomes of untreated MDS patients and aiding design and analysis of clinical trials in this disease.

Better prognosis for patients with del(7q) than for patients with monosomy 7 in myelodysplastic syndrome.

BACKGROUND: Abnormalities involving chromosome 7 are frequent in myelodysplastic syndrome (MDS) and suggest a poor prognosis. METHODS: The authors examined the hypothesis that the clinical features and survival associated with isolated deletion (del) of part of the long arm of chromosome 7 (7q) in MDS are different from those associated with isolated monosomy 7 (complete loss of chromosome 7). In total, 133 patients with a diagnosis of de novo MDS (according to the World Health Organization [WHO] classification) and chromosome 7 abnormalities in the Spanish MDS Registry were evaluated retrospectively. Four karyotypic groups were identified: isolated del(7q) (n = 29), isolated monosomy 7 (n = 27), del(7q) with additional abnormalities (n = 24), and monosomy 7 with additional abnormalities (n = 53). RESULTS: Isolated del(7q) was more frequent in patients with less advanced MDS according to the WHO classification or the International Prognostic Scoring System. In addition, isolated del(7q) was associated with fewer blasts in bone marrow than other cytogenetics groups. Survival was significantly superior in patients with isolated del(7) than in those with isolated monosomy 7, del(7q) with additional abnormalities, or monosomy 7 with additional abnormalities. On multivariate analysis, age, the percentage of blasts in bone marrow, and other chromosome 7 abnormalities apart from isolated del(7q) were identified as independent risk factors for survival. CONCLUSIONS: The current results demonstrated that patients who had MDS with isolated del(7q) had some distinct clinical-pathologic characteristics as well as better survival than patients who had MDS with isolated monosomy 7.

Prognostic impact of severe thrombocytopenia in low-risk myelodysplastic syndrome.

BACKGROUND: Thrombocytopenia is very common in myelodysplastic syndrome (MDS); however, its clinical impact in low-risk patients remains controversial. METHODS: The authors analyzed the incidence and prognostic significance of thrombocytopenia at diagnosis in 2565 de novo MDS patients included in the Spanish MDS Registry. RESULTS: Thrombocytopenia (platelet count <100 × 10(9) /L) was identified in 842 patients (32.8%). Severe thrombocytopenia (platelet count <30 × 10(9) /L) was observed in 7.1% of patients and was significantly associated with a higher-risk World Health Organization subtype (P = .026) and intermediate-2/high-risk International Prognostic Scoring System (IPSS) score (P = .046). Severe thrombocytopenia was the most important prognostic factor and had negative effects on the low/intermediate-1 risk group. Median overall survival of patients with a platelet count <30 and ≥ 30 × 10(9) /L was 16 months and 71 months, respectively (hazard ratio, 4.66; 95% confidence interval, 2.74-7.90; P < .0001). The negative effect of severe thrombocytopenia in low/intermediate-1 risk patients was caused by increased risk of bleeding. CONCLUSIONS: MDS patients with low/intermediate-1 IPSS risk score and severe thrombocytopenia should no longer be regarded as low risk, and must be considered for disease-altering approaches at diagnosis.

Linfocitosis B policlonal persistente: estudio de 35 casos / Persistent polyclonal B-cell lymphocytosis: study of 35 cases

Fundamento y objetivo: La linfocitosis B policlonal persistente (LBPP) es una entidad muy poco frecuente que se relaciona con el tabaquismo e incide especialmente en mujeres. Cursa con aumento de IgM sérica, asociación al haplotipo HLA-DR7, anomalías citogenéticas y múltiples reordenamientos de IgH/BCL-2. Todavía no está clara su naturaleza premaligna o benigna. El objetivo de este trabajo fue analizar las características de la LBPP con especial interés en su evolución. Pacientes y método: Se han estudiado retrospectivamente 35 LBPP de 5 hospitales catalanes. Se realizó una valoración morfológica de las extensiones de sangre por los miembros del Grup Català de Citologia Hematològica (GCCH) en un microscopio de 16 cabezales y se analizaron los datos clínicos y biológicos. Resultados: La LBPP se presentó, en la mayoría de los casos, como linfocitosis en mujeres fumadoras. El distintivo morfológico es la presencia de linfocitos de aspecto activado, en ausencia de enfermedades víricas recientes, y de linfocitos bilobulados y/o hendidos, y algunos con bolsillos nucleares observados por ultraestructura. En la mayoría de los casos estudiados se detectó: aumento policlonal de IgM, expresión del haplotipo HLA-DR7, anomalías cromosómicas como i(3)(q10) y múltiples reordenamientos de IgH/BCL-2. Con una mediana de seguimiento de 70,7 meses, 34 de los 35 pacientes permanecen asintomáticos y vivos, uno falleció por un adenocarcinoma de pulmón y otro desarrolló un linfoma folicular, sin demostración de relación alguna entre éste y la LBPP. Conclusiones: La LBPP presenta un curso estable y asintomático, y se acompaña con frecuencia de alteraciones genéticas. Se desconoce si es una situación premaligna, a semejanza de las gammapatías monoclonales de significado incierto. Por ello, es fundamental una correcta interpretación de la linfocitosis y un seguimiento evolutivo (AU)

Background and objectives: Persistent polyclonal B-cell lymphocytosis (PPBL) is a rare entity, presenting especially in adult smoker women. It is characterized by an increase of serum IgM, DR7-HLA haplotype,cytogenetic abnormalities and multiple IgH/BCL-2 earrangements. To date, it has not been elucidatedwhether this is a benign or premalignant disorder. We analyzed the PPBL characteristics with especial attention to its evolution.Patients and methods: Thirty-five PPBL patients from 5 hospitals in Catalonia were retrospectivelyanalyzed. A simultaneous morphologic review of the blood smears was performed by members of the GCCH in a 16 multiple-observer optic microscope. Clinical and biological data were also analyzed. Results: PPBL presents in the majority of cases with persistent polyclonal B-cell lymphocytosis and affects primarily smoker women. The morphologic hallmark, in absence of viral infections, is the presence of activated lymphocytes with bilobulated and/or cleaved nuclei, and nuclear pockets in theultrastructural study. Increased serum IgM, HLA-DR7 haplotype, chromosomal abnormalities such asi(3)(q10) and multiple IgH/BCL-2 rearrangements were detected. Thirty-four out of 35 patients are alive after a median follow up of 70.7 months. One patient died because of lung adenocarcinoma and another developed a follicular lymphoma without relation to PPBL.Conclusions: PPBL has an asymptomatic and stable evolution, although it frequently presents genetic abnormalities. It remains unknown whether it is a premalignant entity, similar to monoclonal gammopathies of unknown significance. Hence, accurate cytologic diagnosis and follow-up are essential (AU)

[Persistent polyclonal B-cell lymphocytosis: study of 35 cases]. / Linfocitosis B policlonal persistente: estudio de 35 casos.

BACKGROUND AND OBJECTIVES: Persistent polyclonal B-cell lymphocytosis (PPBL) is a rare entity, presenting especially in adult smoker women. It is characterized by an increase of serum IgM, DR7-HLA haplotype, cytogenetic abnormalities and multiple IgH/BCL-2 rearrangements. To date, it has not been elucidated whether this is a benign or premalignant disorder. We analyzed the PPBL characteristics with especial attention to its evolution. PATIENTS AND METHODS: Thirty-five PPBL patients from 5 hospitals in Catalonia were retrospectively analyzed. A simultaneous morphologic review of the blood smears was performed by members of the GCCH in a 16 multiple-observer optic microscope. Clinical and biological data were also analyzed. RESULTS: PPBL presents in the majority of cases with persistent polyclonal B-cell lymphocytosis and affects primarily smoker women. The morphologic hallmark, in absence of viral infections, is the presence of activated lymphocytes with bilobulated and/or cleaved nuclei, and nuclear pockets in the ultrastructural study. Increased serum IgM, HLA-DR7 haplotype, chromosomal abnormalities such as i(3)(q10) and multiple IgH/BCL-2 rearrangements were detected. Thirty-four out of 35 patients are alive after a median follow up of 70.7 months. One patient died because of lung adenocarcinoma and another developed a follicular lymphoma without relation to PPBL. CONCLUSIONS: PPBL has an asymptomatic and stable evolution, although it frequently presents genetic abnormalities. It remains unknown whether it is a premalignant entity, similar to monoclonal gammopathies of unknown significance. Hence, accurate cytologic diagnosis and follow-up are essential.

Cytogenetic risk stratification in chronic myelomonocytic leukemia.

BACKGROUND: The prognostic value of cytogenetic findings in chronic myelomonocytic leukemia is unclear. Our purpose was to evaluate the independent prognostic impact of cytogenetic abnormalities in a large series of patients with chronic myelomonocytic leukemia included in the database of the Spanish Registry of Myelodysplastic Syndromes. DESIGN AND METHODS: We studied 414 patients with chronic myelomonocytic leukemia according to WHO criteria and with a successful conventional cytogenetic analysis at diagnosis. Different patient and disease characteristics were examined by univariate and multivariate methods to establish their relationship with overall survival and evolution to acute myeloid leukemia. RESULTS: Patients with abnormal karyotype (110 patients, 27%) had poorer overall survival (P=0.001) and higher risk of acute myeloid leukemia evolution (P=0.010). Based on outcome analysis, three cytogenetic risk categories were identified: low risk (normal karyotype or loss of Y chromosome as a single anomaly), high risk (presence of trisomy 8 or abnormalities of chromosome 7, or complex karyotype), and intermediate risk (all other abnormalities). Overall survival at five years for patients in the low, intermediate, and high risk cytogenetic categories was 35%, 26%, and 4%, respectively (P<0.001). Multivariate analysis confirmed that this new CMML-specific cytogenetic risk stratification was an independent prognostic variable for overall survival (P=0.001). Additionally, patients belonging to the high-risk cytogenetic category also had a higher risk of acute myeloid leukemia evolution on univariate (P=0.001) but not multivariate analysis. CONCLUSIONS: Cytogenetic findings have a strong prognostic impact in patients with chronic myelomonocytic leukemia.