Search

Burkitt's monomorphic posttransplant lymphoproliferative disorder (B-PTLD) is an uncommon subtype of PTLD. Owing to the paucity of this complication, clinical characteristics and outcome has not been fully described. Clinical characteristics and outcomes of 20 patients diagnosed with B-PTLD from 10 transplant centers belonging to the GEL/TAMO group were reviewed. Median time from transplant to B-PTLD was 7.2 years. All the cases fulfill the morphologic and genetic criteria of B-PTLD, whereas Epstein-Barr virus (EBV) was detected in 70% of cases. Patients were treated with different chemotherapy combinations, and three patients received upfront rituximab monotherapy. The great majority of patients receiving CHOP-like regimens attained a complete response (CR) (73%), similar to that obtained with dose-intensive chemotherapy (83% CR). In contrast, patients receiving upfront rituximab monotherapy required subsequent chemotherapy. Two patients (10%) died during treatment due to infection. The median progression-free survival and overall survival (OS) were 16 months and 139 months, respectively. When analyzing variables predicting for OS, we found that patients with bone marrow involvement had an adverse prognosis, with a median OS of 6 months (p = 0.008). In conclusion, B-PTLD is an uncommon complication usually associated with EBV infection and with an aggressive clinical course, particularly in patients with bone marrow involvement. High-dose chemoimmunotherapy obtained similar responses to R-CHOP, suggesting that R-CHOP could be an adequate alternative for these patients. In contrast, rituximab monotherapy does not seem to be effective enough to control the disease. [ABSTRACT FROM AUTHOR]

Competing Interests: The authors declare no conflict of interest.

Myelofibrosis (MF) is a myeloproliferative neoplasm (MPN) with heterogeneous clinical course. Allogeneic hematopoietic cell transplantation remains the only curative therapy, but its morbidity and mortality require careful candidate selection. Therefore, accurate disease risk prognostication is critical for treatment decision-making. We obtained registry data from patients diagnosed with MF in 60 Spanish institutions (N = 1386). These were randomly divided into a training set (80%) and a test set (20%). A machine learning (ML) technique (random forest) was used to model overall survival (OS) and leukemia-free survival (LFS) in the training set, and the results were validated in the test set. We derived the AIPSS-MF (Artificial Intelligence Prognostic Scoring System for Myelofibrosis) model, which was based on 8 clinical variables at diagnosis and achieved high accuracy in predicting OS (training set c-index, 0.750; test set c-index, 0.744) and LFS (training set c-index, 0.697; test set c-index, 0.703). No improvement was obtained with the inclusion of MPN driver mutations in the model. We were unable to adequately assess the potential benefit of including adverse cytogenetics or high-risk mutations due to the lack of these data in many patients. AIPSS-MF was superior to the IPSS regardless of MF subtype and age range and outperformed the MYSEC-PM in patients with secondary MF. In conclusion, we have developed a prediction model based exclusively on clinical variables that provides individualized prognostic estimates in patients with primary and secondary MF. The use of AIPSS-MF in combination with predictive models that incorporate genetic information may improve disease risk stratification., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)

Real-world evidence comparing the efficacy of chimeric antigen receptor (CAR) T-cell therapy against that of the previous standard of care (SOC) for refractory large B-cell lymphoma (LBCL) is scarce. We retrospectively collected data from patients with LBCL according to SCHOLAR-1 criteria treated with commercial CAR T-cell therapy in Spain (204 patients included and 192 treated, 101 with axicabtagene ciloleucel [axi-cel], and 91 with tisagenlecleucel [tisa-cel]) and compared the results with a historical refractory population of patients (n = 81) obtained from the GELTAMO-IPI study. We observed superior efficacy for CAR-T therapy (for both axi-cel and tisa-cel) over pSOC, with longer progression-free survival (PFS) (median of 5.6 vs. 4-6 months, p ≤ 0.001) and overall survival (OS) (median of 15 vs. 8 months, p < 0.001), independently of other prognostic factors (HR: 0.59 (95% CI: 0.44-0.80); p < 0.001] for PFS, and 0.45 [(95% CI: 0.31-0.64)] for OS). Within the CAR-T cohort, axi-cel showed longer PFS (median of 7.3 versus 2.8 months, respectively, p = 0.027) and OS (58% versus 42% at 12 months, respectively, p = 0.048) than tisa-cel. These differences were maintained in the multivariable analysis. On the other hand, axi-cel was independently associated with a higher risk of severe cytokine release syndrome and neurotoxicity. Our results suggest that the efficacy of CAR-T cell therapy is superior to pSOC in the real-world setting. Furthermore, axi-cel could be superior in efficacy to tisa-cel, although more toxic, in this group of refractory patients according to SCHOLAR-1 criteria., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bastos-Oreiro, Gutierrez, Reguera, Iacoboni, López-Corral, Terol, Ortíz-Maldonado, Sanz, Guerra-Dominguez, Bailen, Mussetti, Abrisqueta, Hernani, Luzardo, Sancho, Delgado-Serrano, Salar, Grande, Bento, González de Villambrosía, García-Belmonte, Sureda, Pérez-Martínez, Barba, Kwon and Martín García-Sancho.)

The use of immunochemotherapy has improved the outcome of follicular lymphoma (FL). Recently, complete response at 30 months (CR30) has been suggested as a surrogate for progression-free survival. This study aimed to analyse the life expectancy of FL patients according to their status at 30 months from the start of treatment in comparison with the sex and age-matched Spanish general population (relative survival; RS). The training series comprised 263 patients consecutively diagnosed with FL in a 10-year period who needed therapy and were treated with rituximab-containing regimens. An independent cohort of 693 FL patients from the Grupo Español de Linfomas y Trasplante Autólogo de Médula Ósea (GELTAMO) group was used for validation. In the training cohort, 188 patients were in CR30, with a 10-year overall survival (OS) of 53% and 87% for non-CR30 and CR30 patients, respectively. Ten-year RS was 73% and 100%, showing no decrease in life expectancy for CR30 patients. Multivariate analysis indicated that the FL International Prognostic Index was the most important variable predicting OS in the CR30 group. The impact of CR30 status on RS was validated in the independent GELTAMO series. In conclusion, FL patients treated with immunochemotherapy who were in CR at 30 months showed similar survival to a sex- and age-matched Spanish general population., (© 2019 British Society for Haematology and John Wiley & Sons Ltd.)

Follicular lymphoma in situ (FLIS) and mantle cell lymphoma in situ (MCLIS) are histopathologic findings of undetermined clinical significance. We studied a series of 341 consecutive lymph node resection specimens from patients diagnosed with colorectal (201 cases) and breast (140 cases) adenocarcinoma between 1998 and 2000. Incidental and isolated FLIS was identified in 11/341 patients (3.23%), whereas incidental and isolated MCLIS was found in 2/341 patients (0.59%). None of these cases developed overt lymphoma. A second series of 17 cases of FLIS (16 cases) and MCLIS (1 case) from consultation files was analyzed. Five cases with incidental and isolated FLIS were identified. None of these cases developed overt lymphoma. Overall, none of the 16 cases with incidental and isolated FLIS in both series developed overt FL after a median follow-up of 54 months (range, 7 to 187 mo). However, 12 of these cases with a clinical suspicion of lymphoproliferative disorder showed the association (in different lymph nodes) or combination (in the same sample) of FLIS or MCLIS with other lymphoid neoplasms (FL, splenic marginal zone lymphoma, nodal marginal zone lymphoma, Hodgkin lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, multiple myeloma). In conclusion, the clinical relevance of FLIS and MCLIS seems to strictly depend on the clinical context. Incidental FLIS or MCLIS seem to have a very low risk for transformation, which recommends careful clinical examination after histopathologic diagnosis and conservative management with follow-up for a limited period of time.

Diffuse large B cell lymphoma (DLBCL) is a heterogeneous group of aggressive lymphomas that can be classified into three molecular subtypes by gene expression profiling (GEP): GCB, ABC and unclassified. Immunohistochemistry-based cell of origin (COO) classification, as a surrogate for GEP, using three available immunohistochemical algorithms was evaluated in TMA-arranged tissue samples from 297 patients with de novo DLBCL treated by chemoimmunotherapy (R-CHOP and R-CHOP-like regimens). Additionally, the prognostic impacts of MYC, BCL2, IRF4 and BCL6 abnormalities detected by FISH, the relationship between the immunohistochemical COO classification and the immunohistochemical expression of MYC, BCL2 and pSTAT3 proteins and clinical data were evaluated. In our series, non-GCB DLBCL patients had significantly worse progression-free survival (PFS) and overall survival (OS), as calculated using the Choi, Visco-Young and Hans algorithms, indicating that any of these algorithms would be appropriate for identifying patients who require alternative therapies to R-CHOP. Whilst MYC abnormalities had no impact on clinical outcome in the non-GCB subtype, those patients with isolated MYC rearrangements and a GCB-DLBCL phenotype had worse PFS and therefore might benefit from novel treatment approaches.

Aims: Here we report two cases of follicular lymphoma that transformed to CD30 positive diffuse large B cell lymphoma and review the literature on this topic., Results: The first case represents an example of early transformation of conventional low-grade follicular lymphoma to CD30-positive large B cell lymphoma. Immunoglobulin (Ig)H and cytogenetic identity was demonstrated between both components. High-dose and auto-stem cell transplant (SCT) was applied and complete response was achieved. The second case represents an example of d'emblee transformation of intrafollicular neoplasia to CD30-positive large B cell lymphoma. Immunoglobulin K deleting element (IgKde) and cytogenetic identity between both phases was demonstrated. The patient was in partial response after four cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP)., Conclusions: CD30 expression was found to be associated in these cases to the transformation event and could be considered a therapeutic target to add to conventional immunochemotherapeutic regimens, even in combination with auto-SCT. We suggest looking for CD30 expression in transformed follicular lymphoma cases., (© 2015 John Wiley & Sons Ltd.)

Aims: CD30-positive primary cutaneous lymphoproliferative disorders include several entities with differing clinical presentation but overlapping histological features, including lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma (C-ALCL). DUSP22-IRF4 locus translocation is present in 20-57% of C-ALCLs, and has also been described in a series of 11 lymphomatoid papulosis patients, where it was associated with a particular biphasic histological pattern, including pagetoid reticulosis-type epidermal infiltration. We aimed to study whether the presence of this translocation may define distinctive histological features in C-ALCL., Methods and Results: We collected three cases of C-ALCL with histological features similar to those described in the new variant of lymphomatoid papulosis with 6p25.3 rearrangement. We studied their histological features and immunophenotype, using a panel of antibodies against CD30, TCR-βF1, TCR-γ, CD4, CD8, CD20, Ki-67 and ALK. FISH analyses were performed using an IRF4-DUSP22 break-apart probe for the study of the 6p25.3 rearrangement. FISH results were positive in the three cases, which all showed distinctive histological and immunohistochemical features: a diffuse dermal infiltrate of atypical medium-to-large cells, and marked epidermotrophism with small, atypical intra-epidermal lymphocytes., Conclusions: Our findings suggest that the presence of 6p25.3 rearrangement might be related to this particular biphasic pattern., (© 2014 John Wiley & Sons Ltd.)