Our results are of interest owing to the absence of data in the literature on anidulafungin use in HSCT patients with GVHD, and suggest that anidulafungin, because of its spectrum, pharmacological profile, low toxicity, and absence of interactions with immunosuppressants, could be a drug of choice in this setting.
Background: Diffuse large B-cell lymphoma (DLBCL) is a clinically and molecularly heterogeneous disease. We can identify two subgroups with aggressive clinical course and higher risk of treatment failure after standard therapy: B cell lymphoma unclassifiable (BCLU) with features intermediate between DLBCL and Burkitt lymphoma (BL) and B-cell lymphomas with double/triple translocation (DHL/THL). Previous reports suggest that these types of lymphomas may show a common immunophenotype, providing another tool in the challenge of their diagnosis. Objetives: To analyze the immnunophenotype (IF) of BCLU and DH/TH lymphomas by multiparametric flow cytometry and compare it with the IF of a series of cases with DLBCL and BL. Methods: we analyzed the inmunophenotype (four-color flow cytometry on a FACSCalibur flow cytometer) and cytogenetic studies (FISH to detect MYC, BCL2 and/or BCL6 rearrangement) of cases diagnosed of BCLU and DH/TH lymphomas. Control cases of DLBCL and BL were consecutively collected from our database. Fisher`s Exact test was used to compare proportions between two groups. P-values <0.05 were considered statistically significant. Results: We analyzed 23 controls (14 DLBCL and 9 BL) and 17 cases: 9 DHL (8 BCL2/MYC+ and 1 BCL6/MYC+), 3 THL (BCL2/BCL6/MYC+) and 5 BCLU (1 IGH-MYC+, 3 MYC+ and 1 unknown). Six of the 17 cases (35.3%) had decreased expression of CD19 while this was exceptional in DLBCL (1/10 P=0.073) and BL (0/9 P=0.054). All of the cases were positive for CD20 but with different intensities: only 5.9% expressed high CD20 compared to 42.9% of DLBCL (p=0.021) and 55.6% of BL (P=0.010). Most of the cases (12/17) had intermediate expression of CD20 and only 4/17 had weak expression. CD10 expression was typical in BL (100%) and frequent in the cases (82.4%), while it was only present in 20% of DLBCL (P<0.0001). CD38 expression was high in 100% of BL, 6.3% of the cases and none of DLBCL. It was intermediate in 64.7% of the cases and in 35.7% of DLBCL (P=0.015). BCL2 overexpression was detected in 57.1% of the cases; neither DLBCL nor BL (P= 0.009) had BCL2 overexpression. Conclusions: We identify a common immunophenotype in DH/TH lymphomas and BCLU: decreased expression of CD19 and CD20, CD10 expression, overexpression of BCL2 and intermediate expression of CD38. This immuphenotype may be useful for identifying cases for confirmatory cytogenetic studies. Larger studies are needed to validate these results. Disclosures No relevant conflicts of interest to declare.
INTRODUCTION: Neurological complications (NC) are frequently reported after allogeneic hematopoietic stem cell transplantation (allo-HSCT), but their incidence, characteristics and impact on the overall survival are not well defined. For this reason, we retrospectively analyzed our experience. PATIENTS AND METHODS: A retrospective study of 506 allo-HSCTs performed in our center from January 2000 to September 2013, including 336 myeloablative and 170 non-myeloablative, 280 sibling and 226 unrelated, and 397 matched and 109 mismatched. All neurological complications, according to NCCN classification, were included. RESULTS: Seventy seven patients developed neurological complications. Their median age was 48 years (5-70) and 43 (56%) were male. Underlying diseases were Acute Leukemia (34), Myelodysplastic Syndrome (11), Multiple Myeloma (9), Non-Hodgkin Lymphoma (7), Myeloproliferative disease (7), Bone marrow Aplasia (5), Hodgkin Lymphoma (2) and other (2). Thirty eight patients (49.4%) were in CR, 14 (18.2%) in PR, 16 (20.8%) had a refractory disease and 9 (11.7%) had a stable disease. Median preceding treatments were 2 (0-10), including in 24 (31.2%) a preceding HSCT (19 autologous and 5 allogeneic). Fifty seven patients (74%) had received a myeloablative (MA) regimen (14 TBI and 43 chemotherapy). Stem cell source was bone marrow, peripheral blood and umbilical cord blood in 53, 20 and 4 patients, respectively. The donor was unrelated in 47 patients (61%) and mismatched in 25 (32.5%). A calcineurin inhibitor (Cyclosporine or Tacrolimus) was included in all cases as GVHD prophylaxis, combined with Methotrexate (37), Mycophenolate (35) and Prednisone (5). Seventy seven patients developed 81 NC (74 central and 7 peripheral). The global incidence was 16%, being more frequently reported in unrelated (21.4% vs. 11.4%, p=0.002) or mismatched (24.5% vs. 13.5%, p=0.007) allo-HSCT. Within the group who developed central NC, 48 patients (65%) had an early onset (less than 100 days after HSCT), which consisted of impairment of consciousness (36 patients), focal syndrome (22 patients) or seizures (16 patients). The etiology was toxic-metabolic in 32 patients (posterior encephalopathy in 10 cases), infectious in 21 (viral 10, fungal 6, bacterial 5), vascular in 12 (Thrombotic Thrombocytopenic Purpura 6, hemorrhagic 4, ischemic 2) and relapse in 9. Within the group who developed peripheral NC, 5 patients (71.5%) had a late onset, which consisted of polyneuropathy. The etiology was infectious in 2 cases (viral) and immune in 5 cases. Twenty four patients are alive (31.2%) with a median follow-up of 10 months (0-110). Excluding relapses, NC was a direct or indirect cause of death in 24 patients (54.5%), due to viral (9) and fungal (8) infections, above all. The development of a NC, specially in the central nervous system, had a negative impact on the overall survival (17 months vs. 40 months; p=0.001) (figure 1) CONCLUSIONS: In our series, the incidence of NC in the setting of allo-HSCT was 16%, being more frequently found with unrelated and mismatched donor. They were associated with high mortality, having a negative impact on the overall survival and becoming a direct or indirect cause of death in more than half of cases. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
INTRODUCTION AND AIMS: Abnormalities of chromosome 1 (chr 1) are frequently found in hematopoietic stem cell disorders, but their impact and prognosis in Myelodysplastic Syndrome (MDS) remains unclear. For this reason, we retrospectively analyzed a large series of patients. MATERIALS AND METHODS: A series of 90 patients with MDS and abnormalities of chr 1 were retrospectively evaluated, coming from the Spanish Registry of MDS (68), Marqués de Valdecilla Universitary Hospital (16) and Azienda Careggi Universitary Hospital (Florence) (6). We compared this group to a control group of 992 patients with MDS and an abnormal karyotype, but without abnormalities of chr 1, included in the Spanish Registry of MDS. RESULTS: Abnormalities of chr 1 occurred in 8.3% of patients with MDS. Fifty seven percent belonged to the high/very high IPSS-R (Revised International Prognostic Scoring System) risk group. The median number of chromosomal abnormalities in the group with and without chr 1 involvement was 3.5 (1-15) and 1 (1-18), respectively (p<0.0001). A complex karyotype was found in 60% and in 16% of patients with and without abnormalities of chr 1, respectively (p<0.0001). The most frequent type of cytogenetic abnormality was translocation (30%). Long arm involvement was seen in 37.8% of patients whereas both arms were only affected in 14.4%. Forty three and thirty one percent of patients with abnormalities of chr 1 had also chr 5 and chr 7 affected, respectively. A low platelet count (<100 x 109/l) was more frequently found in patients with abnormalities of chr 1 (50% vs 32%; p=0.002). According to the number of cytogenetic abnormalities, translocation (43.2%) was the most frequent cytogenetic abnormality observed in the group of ≤2 abnormalities and chr 1 involvement (group 1), becoming chr 7 (16.2%) the most recurrently affected. However, deletion (24.5%) predominated in the group of ≥ 3 abnormalities and chr 1 involvement (group 2). In the first group, long arm was more frequently involved (48.6%) whilst both arms were involved in only 5.5% of cases, being this condition more common in the second group. Moreover, the short arm was mostly restricted to the second group (32.1%). In the first group, chr 5 and chr 7 were affected in 8.1% and 18.9% of cases, respectively, compared to group 2 (67% and 39.6%, respectively). A higher hemoglobin level was observed in the first group (10.6 vs. 9.6 g/dl; p=0.006). However, we observed no differences in terms of bone marrow blasts, platelet count and absolute neutrophil count between these two groups (table 1). The median survival was significantly lower in the group with chr 1 involvement (34.1 vs. 64.7 months; p<0.001). When patients were classified attending to the number of abnormalities, the prognostic impact of chromosome 1 was restricted to the group with ≤2 abnormalities (44.7 vs. 72.2 months; p=0.034) (figure 1). However, we observed no differences in terms of survival in the group with ≥ 3 abnormalities (24 vs. 19 months; p=0.283) (table 1). Transformation to acute myeloid leukemia (AML) was observed in 35.6% of patients with chr 1 involvement, in comparison to the 20.2% of the control group (p=0.001). CONCLUSIONS: Chr 1 involvement in patients with MDS is more frequently associated with complex karyotype, generally with chr 5 and 7 additionally involved and a low platelet count. In those patients carrying a complex karyotype, the presence of chromosome 1 does not provide additional prognostic information. However, in the group of patients with ≤ 2 abnormalities, chr 1 aberrations are associated with a significant reduced OS, suggesting that those should be included in the high risk cytogenetic group. Acknowledgments: Ministerio de Sanidad y Consumo, Spain (PI 11/02010); Red Temática de Investigación Cooperativa en Cáncer (RTICC, FEDER) (RD12/0036/0044); 2014 SGR225 (GRE) Generalitat de Catalunya,Fundació Internacional Josep Carreras, Obra Social “la Caixa” y de Celgene (España). Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.
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