Treatment and outcome analysis of 639 relapsed non-hodgkin lymphomas in children and adolescents and resulting treatment recommendations

Despite poor survival, controversies remain in the treatment for refractory or relapsed pediatric non-Hodgkin lymphoma (r/r NHL). The current project aimed to collect international experience on the re-induction treatment of r/r NHL, hematopoietic stem cell transplantation (HSCT), risk factors associated with outcome, and to suggest treatment recommendations. Inclusion criteria were (i) refractory disease, disease progression or relapse of any NHL subtype except anaplastic large cell lymphoma, (ii) age < 18 years at initial diagnosis, (iii) diagnosis in/after January 2000. Data from 639 eligible patients were evaluable. The eight-year probability of overall survival was 34 ± 2% with highly significant differences according to NHL subtypes: 28 ± 3% for 254 Burkitt lymphoma/leukemia, 50 ± 6% for 98 diffuse large B-cell lymphomas, 57 ± 8% for 41 primary mediastinal large B-cell lymphomas, 27 ± 3% for 177 T-lymphoblastic lymphomas, 52 ± 10% for 34 precursor-B-cell lymphoblastic lymphomas and 30 ± 9% for 35 patients with rare NHL subtypes. Subtype-specific factors associated with survival and treatment recommendations are suggested. There were no survivors without HSCT, except in few very small subgroups. Conclusions: There is an urgent need to further improve survival in r/r NHL. The current study provides the largest real-world series, which underlines the role of HSCT and suggests treatment recommendations. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Translocation t(1;11)(p32;q23) with MLL-EPS15 fusion gene formation in acute leukemias: a review and 6 new case reports. Approaches to minimal residual disease monitoring

We performed clinical and laboratory characterization of patients with rare translocation t(1;11)(p32;q23) leading to MLL-EPS15 fusion gene formation. Study cohort consisted of 33 primary acute leukemia (AL) cases including 6 newly diagnosed and 27 patients previously described in literature. Among study group patients t(1;11)(p32;q23) was found most frequently in infant AL cases (median age 8 months). In acute lymphoblastic leukemia (ALL) male/female ratio was 1:3, in acute myeloid leukemia (AML) it was 1:1. Additional cytogenetic aberrations in 38 % of patients were revealed. The most frequent breakpoint position in EPS15 gene was intron 1. Four different types of MLLEPS15 fusion gene transcripts were detected. Primers-probe-plasmid combination for MLL-EPS15 fusion gene transcript monitoring by realtime quantitative polymerase chain reaction (RQ-PCR) was developed and successfully applied. In 3 patients RQ-PCR was done on genomic DNA for absolute quantification of MLL-EPS15 fusion gene. High qualitative concordance rate (92 %) was noted between minimal residual disease data obtained in cDNA and genomic DNA for MLL-EPS15 fusion detection.</p

Thyroid function in children and adolescents after combined therapy of Hodgkin disease

Thyroid diseases, especially hypothyroidism, are among the most frequent endocrine complications in patients with Hodgkin lymphoma whohave received neck irradiation. Thyroid function was evaluated in 34 patients (11 males and 23 females) after combined chemo radiotherapyof Hodgkin lymphoma according to modified DAL-HD-90M and GPOH-HD-2002 protocols. The median age was 15.9 years (range 5–18 years), the median time from the end of therapy was 1.08 years (range 1 month–4.9 years). 33 patients received radiotherapy to the neck region: 12 children — 20 Gy, 9 — 25 Gy, 10 — 30 Gy, 2 — 35 Gy. These patients were investigated by clinical examination, thyroid ultrasound and thyroid function tests. Thyroid abnormalities were detected in 4 of 21 patients who received 20–25 Gy (1 case of autoimmune thyroiditis and 3 cases of subclinical hypothyroidism) and in 3 of 12 patients who received 30–35 Gy (2 cases of autoimmune thyroiditis and 1 case of subclinical hypothyroidism). Autoimmune thyroiditis also developed in patient who received only 35 Gy mediastinum irradiation. Age, sex, follow-up time, irradiation dose were not significant factors in the thyroid dysfunction development. Thyroid examination must be obligatory part of the follow-up examination of patients with Hodgkin lymphoma.</p

MOLECULAR BIOLOGICAL CHARACTERISTICS OF ALK-POSITIVE ANAPLASTIC LARGE CELL LYMPHOMA

ALK-positive anaplastic large cell lymphoma is a heterogeneous group of mature T-cell non-Hodgkin lymphoma, and is characterized by CD30/Ki-1 expression. Recently, value of various prognostic factors is investigated. These include clinical, histological and molecular genetic changes associated with different signaling pathways activation. Some features of the mechanism of action of anaplastic lymphoma kinases and targeted therapies possibilities addressed in this review

Brentuximab vedotin in children and adolescents with Hodgkin’s lymphoma and anaplastic large cell lymphoma – literature review and own experience

Despite significant advances in the treatment of lymphomas in children remain a small proportion of patients with refractory or recurrent disease. An effective approach to the treatment of such patients – not only is the second line chemotherapy, but the use of the new targeted therapies. An example of this approach is the use of brentuximab vedotin (antibody-drug conjugate directed to the CD30) in relapsed Hodgkin’s lymphoma and anaplastic large cell lymphoma. Literature review and own experience of using this drug in children are describes in this article

Primary diffuse large B-cell lymphoma of the central nervous system (case report and literature review)

The central nervous system (CNS) involvement in patients with non-Hodgkin’s lymphomas is not uncommon, especially in children with mature B-cells lymphomas, unlike the primary CNS lymphoma (PCNSL). PCNSL is a rare extranodal form of NHL that occurs only in the CNS – in the brain, spinal cord, meninges, in the eyes, and not extending beyond CNS. Its frequency in adults is 1–2 % of lymphomas and 5 % of all CNS tumors. Data on prevalence in childhood are not available, limited to some case reports. This article presents a literature review about PCNSL diagnosis and treatment and case report of such lymphoma with intraspinal lesion in 11 years old child

Subcutaneous panniculitis-like T-cell lymphoma in children. Literature review and case reports

Subcutaneous panniculitis-like T-cell lymphoma (SPTL) is a rare tumor from αβ mature cytotoxic T-lymphocytes, which primarily affects the subcutaneous adipose tissue and has morphological manifestations similar to panniculitis. SPTL frequency is less than 1 % of all NHL. It occurs in all age groups, but only 19–20 % are patients younger 20 years. Median age of patients is 35–36 years. To date are only a few cases in children described. In this article we described 3 SPTL cases in patients 1, 10 and 17 years old with typical clinical presentation and detailed analysis.</p

LYMPHOID NEOPLASMS AFTER ALLOGENEIC HEMATOPOIETIC STEM CELLS TRANSPLANTATION. THE CASE OF SECONDARY HODGKIN’S LYMPHOMA, DIFFERENTIAL DIAGNOSIS WITH POST-TRANSPLANT LYMPHOPROLIFERATIVE DISEASE

Secondary malignant diseases are dangerous long-term complications of allogeneic hematopoietic stem cell transplantation (HSCT). This article describes the group of secondary lymphoid neoplasms and presents a rare case of secondary Hodgkin disease in a 21-year patient 6 years after HSCT due to acute myeloid leukemia. This complication should be distinguished from the Hodgkin-like posttransplant lymphoproliferative disease, because of the different therapy approaches and outcomes. We describe their main features and differential diagnostic procedures