Non‐Hodgkin lymphoma following temozolomide

Temozolomide (TMZ) is an oral alkylating agent with significant activity against glioblastoma multiforme (GBM) and melanoma. It increases survival by 2.5 months when used in combination with radiotherapy as an adjuvant therapy in GBM. Secondary MDS/AML or non‐Hodgkin lymphoma attributed to TMZ exposure has been reported. We report a case of non‐Hodgkin lymphoma secondary to temozolomide in a 20‐year‐old female who was treated for GBM with concurrent TMZ and radiotherapy. She developed lymphoma 2 months after completing chemoradiotherapy. Although she was treated with combination chemotherapy for lymphoma, she died of progressive GBM. Pediatr Blood Cancer 2009;53:661–662. © 2009 Wiley‐Liss, Inc.     

Rare non‐Hodgkin lymphoma of childhood and adolescence: A consensus diagnostic and therapeutic approach to pediatric‐type follicular lymphoma,marginal zone lymphoma,and nonanaplastic peripheral T‐cell lymphoma

Pediatric‐type follicular (PTFL), marginal zone (MZL), and peripheral T‐cell lymphoma (PTCL) account each for <2% of childhood non‐Hodgkin lymphoma. We present clinical and histopathological features of PTFL, MZL, and few subtypes of PTCL and provide treatment recommendations. For localized PTFL and MZL, watchful waiting after complete resection is the therapy of choice. For PTCL, therapy is subtype‐dependent and ranges from a block‐like anaplastic large cell lymphoma (ALCL)‐derived and, alternatively, leukemia‐derived therapy in PTCL not otherwise specified and subcutaneous panniculitis‐like T‐cell lymphoma to a block‐like mature B‐NHL‐derived or, preferentially, ALCL‐derived treatment followed by hematopoietic stem cell transplantation in first remission in hepatosplenic and angioimmunoblastic T‐cell lymphoma.     

Children's Oncology Group's 2013 blueprint for research: Non‐Hodgkin lymphoma

Non‐Hodgkin lymphomas account for approximately 7% of cancers diagnosed in patients less than 20 years of age, with approximately 800 cases diagnosed annually at COG institutions. With current therapies, cure rates range from 70% to over 90%, even for children with disseminated disease. However, two major challenges need to be overcome: (i) to optimize upfront treatment to prevent relapse since prognosis for patients with relapsed disease remains poor and (ii) minimize long‐term side effects in survivors. Hence, the future initiatives for the treatment of pediatric NHL are to utilize novel targeted therapies to not only improve outcomes but to decrease bystander organ toxicities and late effects. Pediatr Blood Cancer 2013; 60: 979–984. © 2012 Wiley Periodicals, Inc.     

Response‐dependent and reduced treatment in lower risk Hodgkin lymphoma in children and adolescents,results of P9426: A report from the Children's Oncology Group

Background

Hodgkin lymphoma is highly curable but associated with significant late effects. Reduction of total treatment would be anticipated to reduce late effects. This aim of this study was to demonstrate that a reduction in treatment was possible without compromising survival outcomes.

Methods

Protocol P9426, a response‐dependent and reduced treatment for low risk Hodgkin lymphoma (stages I, IIA, and IIIA₁) was designed in 1994 based on a previous pilot project. Patients were enrolled from October 15, 1996 to September 19, 2000. Patients were randomized to receive or not receive dexrazoxane and received two cycles of chemotherapy consisting of doxorubicin, bleomycin, vincristine, and etoposide. After two cycles, patients were evaluated for response. Those in complete response (CR) received 2,550 cGy of involved field radiation therapy (IFRT). Patient with partial response or stable disease, received two more cycles of chemotherapy and IFRT at 2,550 cGy.

Results

There were 294 patients enrolled, with 255 eligible for analysis. The 8‐year event free survival (EFS) between the dexrazoxane randomized groups did not differ (EFS 86.8 ± 3.1% with DRZ, and 85.7 ± 3.3% without DRZ (P = 0.70). Forty‐five percent of patients demonstrated CR after two cycles of chemotherapy. There was no difference in EFS by histology, rapidity of response, or number of cycles of chemotherapy. Six of the eight secondary malignancies in this study have been previously reported.

Conclusions

Despite reduced therapy and exclusion of most patients with lymphocyte predominant histology, EFS and overall survival are similar to other reported studies. The protocol documents that it is safe and effective to reduce therapy in low‐risk Hodgkin lymphoma based on early response to chemotherapy with rapid responding patients having the same outcome as slower‐responding patients when given 50% of the chemotherapy. Pediatr Blood Cancer 2012; 59: 1259–1265. © 2012 Wiley Periodicals, Inc.     

Variant histology,IgD and CD30 expression in low‐risk pediatric nodular lymphocyte predominant Hodgkin lymphoma: A report from the Children's Oncology Group

1 Background

Histologic prognostic factors have been described for nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). This study examines histologic and immunophenotypic variants in a clinical trial for pediatric NLPHL.

2 Procedure

One hundred sixty‐eight cases of localized NLPHL were examined for histologic variants, CD30 and immunoglobulin D (IgD) expression, and outcome. Histologic types were scored categorically as 0 = 0, 1 ≤ 25%, and 2 > 25% of the sample.

3 Results

Fifty‐eight (35.1%) cases showed only typical nodular with or without serpiginous histology (types A and B). The remainder showed mixtures of histologies. The numbers of patients with score 2 are 85 (50.6%) type A, 21 (12.5%) type B, 46 (27.4%) with extranodular large B cells (type C), 3 with T‐cell‐rich nodular pattern (type D), 55 (32.7%) with diffuse T‐cell‐rich (type E) pattern, and 2 (1.2%) with diffuse B‐cell pattern (type F). Higher level of types C (P = 0.048) and D (P = 0.033) resulted in lower event‐free survival (EFS). Cytoplasmic IgD was found in 65 of 130 tested (50%), did not significantly associate with EFS but positively correlated with types C and E histology (P < 0.0001) and negatively correlated with types A (P = 0.0003) and B (P = 0.006). Seventeen (10%) expressed CD30, with no adverse effect.

4 Conclusions

Variant histology is common in pediatric NLPHL, especially types C and E, which are associated with IgD expression. Type C variant histology and possibly type D are associated with decreased EFS, but neither IgD nor CD30 are adverse features. Variant histology may warrant increased surveillance, but did not affect overall survival.     

Children's Oncology Group's 2013 blueprint for research: Hodgkin lymphoma

In childhood Hodgkin lymphoma, estimated 5 years survival rates exceed 90%. Long‐term survival continues to decline from delayed toxicities. Key findings from recent Children's Oncology Group trials include: (1) Radiotherapy selection may be based on early chemotherapy response assessed by both FDG‐PET and CT imaging, (2) A new prognostic factor score stratifies patients into risk categories; and (3) novel retrieval regimens were identified. A phase I/II trial is investigating Brentuximab vedotin (Bv) with gemcitabine in relapsed patients. A phase 3 trial will modify conventional chemotherapy and radiotherapy approaches through the addition of Bv, while incorporating translational biology to identify molecular targets. Pediatr Blood Cancer 2013; 60: 972–978. © 2012 Wiley Periodicals, Inc.     

Mapping the Epidemiology of Kaposi Sarcoma and Non‐Hodgkin Lymphoma Among Children in Sub‐Saharan Africa: A Review

Children with human immunodeficiency virus (HIV) have an increased risk of developing Kaposi Sarcoma (KS) and non‐Hodgkin lymphoma (NHL) compared to HIV‐negative children. We compiled currently published epidemiologic data on KS and NHL among children in sub‐Saharan Africa (SSA). Among countries with available data, the median incidence of KS was 2.05/100,000 in the general pediatric population and 67.35/100,000 among HIV‐infected children. The median incidence of NHL was 1.98/100,000 among the general pediatric population, while data on NHL incidence among HIV‐infected children were lacking. Larger regional studies are needed to better address the dearth of epidemiologic information on pediatric KS and NHL in SSA.     

IRF4 translocation status in pediatric follicular and diffuse large B‐cell lymphoma patients enrolled in Children's Oncology Group trials

Large B‐cell lymphoma with IRF4 rearrangement is a provisional entity in the 2017 World Health Organization classification. In order to characterize these lymphomas in children from the United States, IRF4 FISH and immunohistochemical stains were performed on 32 follicular lymphoma and diffuse large B‐cell lymphoma (DLBCL) from Children's Oncology Group studies. Two DLBCLs (6%) had IRF4 rearrangements, one involving the ileocecal valve and another involving the tonsil and cerebrospinal fluid. Both cases had strong, diffuse IRF4/MUM1 immunohistochemical staining, which may be a pathologic clue to the diagnosis. Reclassification of these cases may have prognostic and therapeutic implications.