Seroprevalence study prior and post vaccination in cancer patients in principality of Andorra (COVONCO study).

BACKGROUND: COVID-19 serologic response in patients with cancer may be lower than in the general population and may be influenced by the type of tumor or anticancer treatment. This study aims to analyze serological response prior and after vaccination of COVID-19 within the oncological population in Andorra. We set out to identify risk factors for a higher or lower serological response. PATIENTS AND METHODS: Observational, unicentric, prospective cohort study of oncologic patients in Andorra. We calculated the seroprevalence of antibodies against SARS-CoV-2 (May 2020-June 2021) and analyzed the main demographic, oncologic features and factors associated with being seropositive. RESULTS: A total of 373 patients were analyzed, mainly with solid tumours (n = 334, 89.5%). At baseline, seroprevalence was 13%, increasing during follow-up to 19%; lower seroprevalence was observed in patients with hematologic malignancies (2.6% vs 14.2%; p = 0.041) and patients receiving biological therapies (0% vs 15%, p = 0.005). In the overall seroprevalence analysis, women (23% vs 11.9%; p = 0.006) and tumour-free patients (p = 0.034) showed higher seroprevalence. The multivariable analysis showed that odds of being seropositive were higher among women (OR: 2.44, 95% CI 1.28-4.64), and patients who underwent surgery (OR: 3.35, 95% CI 1.10-10.20). About 80% of the cohort received at least one dose of COVID-19 vaccination, showing a higher seroprevalence of patients who received ChAdOx1-S than those who received BNT162b2 (24.4% vs 6.4%: p = 0.001). CONCLUSION: The seroprevalence of antibodies against SARS-COV-2 in oncologic patients in Andorra was higher among females and patients who received hormonal therapy and surgery while patients with hematologic malignancies and biologic therapies showed lower seropositivity without finding differences in the type of tumour or anticancer treatment.

Intravascular Large B-Cell Lymphoma Genomic Profile Is Characterized by Alterations in Genes Regulating NF-κB and Immune Checkpoints.

Intravascular large B-cell lymphoma (IVLBCL) is an uncommon lymphoma with an aggressive clinical course characterized by selective growth of tumor cells within the vessels. Its pathogenesis is still uncertain and there is little information on the underlying genomic alterations. In this study, we performed a clinicopathologic and next-generation sequencing analysis of 15 cases of IVLBCL using a custom panel for the detection of alterations in 68 recurrently mutated genes in B-cell lymphomagenesis. Six patients had evidence of hemophagocytic syndrome. Four patients presented concomitantly a solid malignancy. Tumor cells outside the vessels were observed in 7 cases, 2 with an overt diffuse large B-cell cell lymphoma. In 4 samples, tumor cells infiltrated lymphatic vessel in addition to blood capillaries. Programmed death-ligand 1 (PD-L1) was positive in tumor cells in 4 of 11 evaluable samples and in macrophages intermingled with tumor cells in 8. PD-L1 copy number gains were identified in a higher proportion of cases expressing PD-L1 than in negative tumors. The most frequently mutated gene was PIM1 (9/15, 60%), followed by MYD88L265P and CD79B (8/15, 53% each). In 6 cases, MYD88L265P and CD79B mutations were detected concomitantly. We also identified recurrent mutations in IRF4 , TMEM30A , BTG2 , and ETV6 loci (4/15, 27% each) and novel driver mutations in NOTCH2 , CCND3 , and GNA13 , and an IRF4 translocation in 1 case each. The mutational profile was similar in patients with and without evidence of hemophagocytic syndrome and in cases with or without dissemination of tumor cells outside the vessels. Our results confirm the relevance of mutations in B-cell receptor/nuclear factor-κB signaling and immune escape pathways in IVLBCL and identify novel driver alterations. The similar mutational profile in tumors with extravascular dissemination suggests that these cases may also be considered in the spectrum of IVLBCL.

Clonal evolution in chronic lymphocytic leukemia: analysis of correlations with IGHV mutational status, NOTCH1 mutations and clinical significance.

Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disorder characterized with highly variable clinical course. The most common chromosomal abnormalities in CLL, using conventional and molecular cytogenetics, are trisomy 12, del(13)(q14), del(11)(q22-23), del(17)(p13), and del(6)(q21). Whereas the prognostic marker such as IGHV mutational status remains stable during course of the diseases, chromosomal aberrations may be acquired over time. The aim of this study was to determine the incidence, and biological significance of clonal evolution (CE) using conventional and molecular cytogenetics and its relationship with prognostic markers such as CD38, ZAP70, and the mutational status of IGHV and NOTCH1. One hundred and forty-three untreated CLL patients were included in the study. The median time interval between analyses was 32 months (range 6-156 months). Forty-seven patients (33%) had CE as evidenced by detection of new cytogenetic abnormalities during follow-up. CE was not correlated with high expression of ZAP70, unmutated IGHV genes or NOTCH1 mutations. Multivariate analysis revealed that CE and IGHV mutation status had a significant impact on TFS. The combination of conventional and molecular cytogenetics increased the detection of CE, this phenomenon probably being a reflection of genomic instability and conferring a more aggressive clinical course.

Different distribution of NOTCH1 mutations in chronic lymphocytic leukemia with isolated trisomy 12 or associated with other chromosomal alterations.

Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults in Western countries. Chromosomal abnormalities commonly found using conventional cytogenetics and FISH are del(11)(q22-23), trisomy 12, del(13)(q14), and del(17)(p13). Trisomy 12 is the most frequent numerical abnormality in CLL. It can appear isolated or associated with other chromosomal aberrations, including t(14;18)(q32;q21) and trisomy 18. The aim of this study was to determine whether CLL patients with isolated trisomy 12 or associated with other chromosomal alterations have different clinico-pathological features, including a different distribution NOTCH1 mutation. Patients were classified into four groups: Group 1, isolated trisomy 12 (n=14); Group 2, trisomy 12 plus trisomy 18 (n=4); Group 3, trisomy 12 plus t(14;18) (n=8); and Group 4: patients with trisomy 12 plus other abnormalities not involving BCL2 (n=28). The Binet stage and expression of ZAP70 were significantly different among cytogenetic groups. NOTCH1 mutations were detected in 6/12 (50%) patients from Group 1, 4/25 (16%) patients from Group 4, and in no patient from groups 2 and 3 (P=0.020). Patients in Group 2 had a more rapid disease progression (median Treatment-free Survival 2 months) as against patients from Groups 1 (50 months), 3 (69 months), or 4 (68 months; P=0.001). These findings indicate that the distribution of NOTCH1 mutations in CLL with trisomy 12 is heterogeneous and that the presence of additional chromosomal abnormalities such as trisomy 18 could change the prognosis of these patients.

Transfusion intensity, not the cumulative red blood cell transfusion burden, determines the prognosis of patients with myelodysplastic syndrome on chronic transfusion support.

Transfusion-dependency is associated with poor prognosis in patients with MDS although the causal link for such association is disputed. This study tests thee hypotheses on the association between transfusion burden and prognosis in the MDS: (1) the cumulative transfusion burden is a confounder merely reflecting the time elapsed from diagnosis; (2) it is a surrogate for higher transfusion intensity, which would reflect a more severe disease; and (3) it is the total amount of transfused RBC units that influences on prognosis. We studied 191 transfusion-dependent patients with MDS or chronic myelomonocytic leukemia. Transfusion intensity was calculated at the time of each transfusion as the yearly-equivalent number of RBC units. The main outcome was acute leukemia-free survival from first transfusion. Median transfusion burden was 30 (range: 4-330) RBC units and 112 patients received ≥ 25 units after a median of 9 months from first transfusion. In nested Cox models, having received ≥ 25 RBC units had a significant effect on survival (P < 0.001) that was not abrogated by including follow-up ≥ 9 months as a time-dependent covariate. Including transfusion intensity in the model had a significant effect on leukemia-free survival (P < 0.001) and cancelled the prognostic value of having received ≥ 25 RBC units. In conclusion, transfusion intensity, instead of the cumulative transfusion burden, is the transfusion-related variable really influencing on the prognosis of patients with transfusion-dependent MDS.

Oxaliplatin-induced immune hemolytic anemia: a case report and review of the literature.

We report a 59-year-old woman diagnosed with metastasic colorectal cancer who developed immune hemolytic anemia during FOLFOX chemotherapy (oxaliplatin/leucovorin/5-fluorouracil). Immunohematologic studies demonstrated that immune hemolysis was oxaliplatin-mediated. On the basis of this case and in a review of the literature in which 13 cases of previously reported oxaliplatin-induced immune cytopenia have been identified, we suggest some clinical clues regarding the use of oxaliplatin in cancer patients.

Abdominal computed tomography predicts progression in patients with Rai stage 0 chronic lymphocytic leukemia.

PURPOSE: Whether computed tomography (CT) should be routinely included in the diagnostic work-up in patients with chronic lymphocytic leukemia (CLL) has not yet been determined. The aim of this study was to analyze the prognostic significance of abdominal CT in patients with CLL in Rai clinical stage 0. PATIENTS AND METHODS: Abdominal CT was performed at diagnosis in 140 patients consecutively diagnosed with CLL in Rai stage 0 disease. RESULTS: An abnormal abdominal CT was found in 38 patients (27%). Abnormal CT correlated with increased bone marrow infiltration (P = .024), high lymphocyte count (P = .001), increased ZAP-70 expression (P = .003), and short lymphocyte doubling time (LDT; P = .007). Patients with abnormal CT progressed more frequently and had a shorter time to progression than those with normal CT (median, 3.5 years v not reached, respectively; P < .001) and required earlier treatment intervention. In a multivariate analysis, only high ZAP-70 expression (relative risk = 3.60) and an abnormal abdominal CT (RR = 2.71) correlated with disease progression. CONCLUSION: In this series, an abnormal abdominal CT was a strong predictor of progression in patients with early-stage CLL. The inclusion of CT scans in the initial work-up of patients with early clinical stage on clinical grounds can, therefore, provide relevant clinical information.

Fludarabine, cyclophosphamide and mitoxantrone in the treatment of resistant or relapsed chronic lymphocytic leukaemia.

We evaluated the efficacy and toxicity of fludarabine combined with cyclophosphamide and mitoxantrone (FCM) in patients with relapsed or resistant chronic lymphocytic leukaemia (CLL). In total, 37 patients with recurrent or resistant CLL received FCM: fludarabine 25 mg/m2 intravenously (IV), d 1-3; cyclophosphamide 200 mg/m2 IV, d 1-3; and mitoxantrone 6 mg/m2 IV, d 1, at 4-week intervals for up to six courses. Moreover, 23 patients received FCM with cyclophosphamide 600 mg/m2 i.v. and mitoxantrone 8 mg/m2 i.v. on d 1. In addition to clinical methods, response was assessed using cytofluorometric and molecular techniques. 'In vitro' sensitivity to the FCM regimen was also analysed in 20 samples. The median number of courses given was 3 (range: 1-6). Overall, 30 patients (50%) achieved complete response (CR), including 10 cases of negative minimal residual disease (MRD(-)) (17%), and 17 (28%) partial response (PR). The median duration of response was 19 months. 'In vitro' sensitivity also correlated with CR achievement (P = 0.04). Main toxicity consisted of neutropenia, infections (8% of courses), and nausea and vomiting. The treatment-related mortality was 5%. FCM did not hamper stem cell harvesting in patients who were candidates for autologous stem cell transplantation. FCM induced a high CR rate, including an important number of MRD(-), in patients with previously treated CLL.

Limitations of Gallium-67 SPECT in histological transformation of chronic lymphocytic leukaemia: an analysis of 13 patients with clinically suspected Richter's syndrome.

Gallium-67 single photon emission computerized tomography (Ga-67 SPECT) was performed in 13 chronic lymphocytic leukaemia (CLL) patients suspected of evolution into diffuse large B-cell lymphoma (DLCL) or Richter's syndrome (RS). Six positive and nine negative Ga-67 SPECTs were observed. Ten patients were biopsied (five in each group). DLCL was not detected in any Ga-67-positive patient, including those in whom Ga-67-positive areas were biopsied. The only case of DLCL was demonstrated in a Ga-67-negative patient. The tumoral proliferative index (Ki67 antigen expression) was moderate and similar in both groups of patients. These results illustrate the limitations of Ga-67 SPECT in identifying RS.