Non-lymphoblastic non-Hodgkin Lymphoma Research Articles

Outcome of Early Stage Pediatric Non-Lymphoblastic Non-Hodgkin Lymphoma.

There is lack of data on outcome of limited stage pediatric non-Hodgkin lymphoma (NHL) from south Asia. In view of this lacuna, authors evaluated patients of early stage (stage 1 and 2) non-lymphoblastic pediatric NHL patients treated with uniform short course, reduced-intensity protocol from Jan 2003 through Dec 2016. Of the total 280 subjects with pediatric NHL, 50 were of early stage of which 42 received uniform protocol. B-cell subtype was observed in 83% patients. Event-free-survival (EFS) and overall-survival (OS) were 85% and 90% respectively at 5 y (median-not reached). Age > 13 y emerged as the only poor risk factor for EFS (p = 0.05) on univariate analysis and same had a trend toward inferior prognosis in OS (p = 0.09). Vincristine-induced neuropathy occurred in five patients. Febrile neutropenia was observed in 16% subjects with one patient requiring hospitalization. There was no treatment-related death. This largest data of limited stage pediatric non-lymphoblastic NHL from south Asia highlights that good outcomes may be achieved with less intense short course therapy without hospitalization, and that adolescent age is the only poor prognostic factor for outcome.

Non-Hodgkin lymphoma in children: Is 1 g/m2 methotrexate as effective as 5 g/m2 in advanced-stage nonlymphoblastic non-Hodgkin lymphoma?

10043 Background: Survival rates in non-Hodgkin lymphoma (NHL) have increased significantly in the last decades. This study aims to assess the demographic data and treatment results of children with nonlymphoblastic NHL treated in a single institution. Methods: 106 children (74 male, 32 female), treated in Istanbul University, Oncology Institute, between 9/1989-12/2012 were evaluated retrospectively. Nonlymphoblastic NHL received COMP until 1991. After then, all received BFM protocols. They received BFM 90 protocol with 5 g/m2 methotrexate (MTX) until 1995 and modified BFM protocol with 1 g/m2 MTX thereafter. Results:The median age was 8(2-19) years. Histopathologic subtypes: 81 Burkitt, 25 large cell. The primary location was abdomen in 51, mediastinum 4, head/neck 31, 20 other (bone 8, breast 2, ovaries 2, skin 2, paravertebral 2, other 4). Bone marrow was involved in 10, CNS in 2. 40 patients had stage I+II, 44 stage III, and 22 stage IV disease. 23 patients died, 7 due to toxicity, 2 with second malignancies (AML,GBM). 10 year survival and EFS in the whole group was 76 and 76 % respectively. 10 year survival was 100, 94.3, 71.3 and 50% in stage I, II, III, and IV. In advanced stage nonlymphoblastic NHL patients, 10 year survival was significantly higher in patients receiving BFM regimen with 1 g/m2 MTX, than in ones receiving COMP or BFM protocol with 5 g/m2 MTX (10 year S, 81%, 46.7%, 44.4% respectively). These results were also compared with 47 advanced stage nonlymphoblastic NHL patients treated with 5 g/m2 BFM protocol in another center in the same university in the same time period (5 year S 78 %). Conclusions: Survival rates in the whole group are in parallel with advances attained in the world in NHL. The significantly higher survival rates achieved in patients with advanced stage non-lymphoblastic patients receiving modified BFM (1g/m2MTX) may be due to the decreased toxicity seen in this group and to the advances in supportive care in the last decade. In another major center in the same university that used the same protocol with 5 g/m2 MTX in the same time period, similar survival rates suggest that 1 g/m2 MTX which is cheaper and less toxic is also as effective as 5 gr/m2 in these patients.

Pediatric Nonlymphoblastic Non-Hodgkin Lymphoma: Baseline, Interim, and Posttreatment PET/CT versus Contrast-enhanced CT for Evaluation—A Prospective Study

To prospectively examine the roles of positron emission tomography (PET)/computed tomography (CT) and conventional contrast material-enhanced CT at baseline, after two cycles of chemotherapy, and after completion of chemotherapy in pediatric patients with nonlymphoblastic non-Hodgkin lymphoma (NHL) who were treated with similar standard treatment protocols. The institutional ethics committee approved the study protocol, and all patients were enrolled after written informed consent was obtained. Patients with nonlymphoblastic NHL were prospectively enrolled between January 2008 and March 2010. Patients underwent contrast-enhanced CT and PET/CT for staging and for response assessment after two cycles of chemotherapy (interim) and treatment completion. Complete metabolic response versus no metabolic response at PET/CT and complete response versus no complete response at contrast-enhanced CT was analyzed by using Kaplan-Meier survival analysis. The final study included 34 patients with nonlymphoblastic NHL (median age, 10.5 years). Baseline PET/CT and contrast-enhanced CT showed concordance in depiction of 112 disease sites; PET/CT depicted 18 more disease sites and two fewer disease sites than contrast-enhanced CT (P = .0003). Disease in five of 34 patients was upstaged, and disease in no patient was downstaged at PET/CT. There was 100% (four of four) concordance between bone marrow involvement at biopsy and stage at PET/CT. The median length of follow-up was 20.3 months. Response at interim PET/CT and contrast-enhanced CT could not predict progression-free survival (PFS) (P = .083 and .18, respectively) or overall survival (OS) (P = .159 and.08, respectively). Posttreatment PET/CT and contrast-enhanced CT findings could predict PFS (P = .036 and .002, respectively) and posttreatment contrast-enhanced CT findings could predict OS (P = .035); however, posttreatment PET/CT findings could not predict OS (P = .067). PET/CT depicts additional sites compared with contrast-enhanced CT and results in upstaging of disease. Either PET/CT or contrast-enhanced CT may be used for response assessment and prognostication in stage III or IV nonlymphoblastic pediatric NHL.

Treatment of children with B‐cell non‐Hodgkin lymphoma in a low‐income country

An adapted LMB 96 derived protocol for B-cell non-Hodgkin lymphoma (NHL) was implemented at the pediatric oncology unit of the Children Welfare Teaching Hospital in Baghdad (Iraq) from 2000 to present. The purpose was to evaluate the feasibility and efficacy of this intensive therapeutic regimen in a limited resource country. Patients <15 years of age with high grade B-cell NHL were included. A modified LMB 96 regimen was employed with a reduction of cyclophosphamide and methotrexate dosages due to inadequate laboratory facilities and supportive care. Between 2000 and 2005, 261 children with non-lymphoblastic NHL were registered; 239 were eligible for the analysis. Two patients had stage I disease, 20 stage II, 179 stage III, and 38 stage IV. Fifty-two patients (22%) had bulky disease. Twelve children were assigned to therapeutic group A (low risk), 184 to group B (intermediate risk), and 43 to group C (high risk). One hundred and eighty-four patients (77%) had a complete response after the COP pre-phase. Sixty-nine patients (29%) died during treatment. Twenty-nine patients abandoned treatment. At 24 months, the overall survival rate of the entire patient population was 66% (CI 95%: 62.2-70.6) and the event-free survival rate 53.3% (CI 95%: 50.0-56.8). The treatment schedule proved effective, but the treatment-related mortality due to infections and metabolic complications was very high owing to the limited supportive care available. The high rate of treatment abandonment was also an important cause of failure, especially for children living far away from the hospital.

High-Dose Cyclophosphamide-High-Dose Methotrexate with Coordinated Intrathecal Therapy for Advanced Nonlymphoblastic Lymphoma of Childhood

The Pediatric Oncology Group (POG) investigated a high-dose cyclophosphamide (CPM) high-dose methotrexate (MTX) regimen to determine therapeutic efficacy in confirmed advanced nonlymphoblastic non-Hodgkin's lymphoma (NHL) (stages III and IV) and B-cell acute lymphatic leukemia (B-ALL) in children. Another goal was to determine the comparative effectiveness of shortened maintenance treatment (2 versus 6 courses) in the study population. Systemic induction therapy included vincristine, prednisone, cyclophosphamide, and intermediate-dose MTX with leucovorin rescue. Superimposed intrathecal (IT) therapy included cytosine arabinoside for 2 successive days followed on day 3 by MTX. Intrathecal MTX was given 3 times during induction. At the end of induction, 2 days of triple (hydrocortisone, MTX, and cytosine arabinoside) therapy were given intrathecally (TIT). All patients then received a consolidation course of 4 doses of TIT, 2 doses of cyclophosphamide, and 4 more courses of vincristine and MTX with leucovorin rescue. Patients were then randomized to receive either 2 or 6 cycles of vincristine plus MTX with leucovorin rescue. The TIT was given with each cycle. Complete response rates by histology and Murphy stage (1) were as follows: undifferentiated lymphoma (DUL) stage III, 84/105 (80%): stage IV, 5/12 (42%); and other NHL [primarily large cell lymphoma (LCL)] stage III, 21/28 (75%); stage IV, 2/3 (67%). Event-free survival (EFS) at greater than 2 years was similar for patients with DUL and LCL, i.e., 65 and 61%, respectively. No significant difference in outcome was noted between patient groups receiving 2 or 6 maintenance treatments (p = .76). Treatment was notable for its modest toxicity following the early change to single-dose CPM therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Primary large-cell lymphoma of the thymus: A diffuse B-cell neoplasm presenting as primary mediastinal lymphoma

Primary mediastinal nonlymphoblastic non-Hodgkin's lymphoma (NLNHL) has distinct clinical, histologic (diffuse large-cell morphology, often with sclerosis and clear cytoplasm), and immunohistochemical features (predominantly B-cell lineage, usually immunoglobulin-negative), which suggest origin from a unique B-cell population. The thymus has a resident population of B cells with a unique immunophenotype, and can be involved by primary mediastinal NLNHL, in some cases selectively. Fifteen cases of NLNHL involving the thymus were studied by paraffin-section immunohistochemistry using antibodies to formalin-resistant epitopes of B cells (4KB5 [CD45RA] and L26 [CD20]) and T cells (L60 [CD43] and UCHL1 [CD45RO]). All were diffuse large-cell or immunoblastic lymphomas with sclerosis, and were also similar to primary mediastinal NLNHL in clinical features. Neoplastic cells stained with L26 in all but one case, which stained with 4KB5 and an antibody to a leukocyte-common antigen (PD7/26 [CD45RB]), and were uniformly nonreactive with L60 (with one exception) and UCHL1. Intermingled small lymphocytes were uniformly L26-negative and positive for T-cell markers, even in one case with atypia suggesting a lymphoma of mixed morphology. These findings demonstrate that primary thymic and primary mediastinal NLNHL are similar B-lineage neoplasms, and support previous suggestions that both may originate in thymic B cells.

The Murphy-Bowman protocol in the treatment of childhood non-Hodgkin's lymphoma.

AbstractTwenty‐two consecutive previously untreated children with stage III and IV non‐lymphoblastic non‐Hodgkin's lymphoma (NHL) and with B‐acute lymphoblastic leukemia (B‐ALL) were treated according to the Murphy‐Bowman protocol. The remission rate was 82%. The estimated long‐term survival rate was 49% and the event‐free survival 41% (in stage III 57% and 53% and in stage IV and B‐ALL 20% and 0%, respectively). The protocol is effective in stage III but fails in stage IV and B‐ALL, which corresponds to the results obtained by other investigators using this or similar protocols.(Acta Paediatr Jpn 1988; 30: 204–208)