Factors contributing to the prognostic significance of bone marrow involvement in childhood non‐Hodgkin lymphoma

Abstract

To evaluate the clinical characteristics and treatment outcome of childhood non-Hodgkin lymphoma (NHL) cases with bone marrow involvement, we studied 13 lymphoblastic, 15 small noncleaved cell, and 8 large cell cases with tumor cells in their marrow. They represented 16%, 11%, and 9% of consecutive NHL cases with these respective histologic subtypes. The treatment outcome differed significantly according to histologic subtype--the 5-year event-free survivals (EFS +/- SE) for large cell NHL, small non-cleaved cell NHL, and lymphoblastic NHL cases were 11 +/- 8%, 40 +/- 20%, and 62 +/- 15%, respectively. Increased serum lactate dehydrogenase (LDH) levels (> 500 U/L) were associated with a poorer EFS (5-year EFS, 0% vs. 50 +/- 10%; P < 0.001). Children < or = 5 years of age had a poorer EFS survival than older children (5-year EFS, 14 +/- 9% vs. 44 +/- 10%; P = 0.03). The degree of bone marrow involvement (< 5% vs. > or = 5%) and race were not significantly associated with treatment outcome. Although intensive chemotherapy has substantially improved survival for patients with advanced stage lymphoblastic or small noncleaved cell lymphoma, patients with large cell NHL and associated marrow involvement continue to have a dismal outcome and require novel or more intensive therapy.

Second malignancy after treatment of childhood non-Hodgkin lymphoma

“…11 Since June 1978, patients with advanced disease have been treated on protocols designed for specific histologic subtypes of disease. 6,7,13 Patients with lymphoblastic lymphomas were treated intensively with multiagent chemotherapy, similar to that for patients with high-risk, acute lymphoblastic leukemia (ALL), given over a long period (18 -30 months). Epipodophyllotoxins were introduced into the treatment regimens during this period for patients with lymphoblastic diseases.…”

Minimal Disseminated Disease in Childhood T-Cell Lymphoblastic Lymphoma: A Report From the Children's Oncology Group

“…1,2 In most cases, lymphoma cells express markers associated with thymic differentiation, including T-cell markers and terminal deoxynucleotidyl transferase (TdT), [3][4][5] hence the classification of T-cell lymphoblastic lymphoma (T-LL). 1,7,8 However, distinguishing lymphoma cells from normal lymphocytes and lymphoid progenitors is difficult, and the true extent of disease dissemination in patients with T-LL is unclear. 6 More than 80% of patients with T-LL do not have marrow involvement at diagnosis by morphologic examination of bilateral marrow aspirates and biopsies.…”

Lymphoid Infiltrates in B Cell Non Hodgkin’s Lymphoma: Comparing Nuclear Characteristics between Lymph Node and Bone Marrow; and Evaluating Diagnostic Features of Bone Marrow Infiltrates in Paraffin Embedded Tissues

“…The frequency with which papers report discordance [8,[12][13][14][15][16]] supports this idea. On balance the overall poorer prognosis conveyed by bone marrow involvement in B cell non Hodgkin's lymphoma [1,2,[6][7][8][9][10] suggests that the discordant bone marrow lesions are neoplastic infiltrates of low grade, perhaps acting as a reservoir for late relapse following chemotherapy. Some studies have however noted no significant difference in prognosis between cases showing lymph node involvement alone and cases showing lymph node involvement with additional discordant bone marrow infiltrates [8,17].…”

“…The distinction of non Hodgkin's lymphoma from benign lymphoid aggregates in bone marrow trephines is difficult and is traditionally based on features such as morphologically abnormal lymphoid cells, the presence of lymphoma at other sites, paratrabecular location of lymphoid aggregates within the bone marrow biopsy, and decreased reticulin at the sites of the lymphoid aggregates. Several studies have previously noted these changes [1][2][3][4][5] and it is generally held that the presence of neoplastic lymphoid infiltrates within the marrow in cases of high-grade nodal B cell non Hodgkin's lymphoma conveys a worse prognosis but this is not true for many low-grade B cell lymphomas in which bone marrow infiltration is part of the disease spectrum [1,[5][6][7][8][9][10]. Our aim was to apply quantitative techniques to benign and neoplastic lymphoid infiltrates to establish (i) if objective parameters could be used as a diagnostic tool when assessing bone marrow trephines and (ii) to evaluate differences in nuclear morphometry and morphology between lymph node and bone marrow samples in B cell non Hodgkin's lymphoma.…”