Results of the randomized Intergroup trial Inter-B-NHL Ritux 2010 for children and adolescents with high-risk B-cell non-Hodgkin lymphoma (B-NHL) and mature acute leukemia (B-AL): Evaluation of rituximab (R) efficacy in addition to standard LMB chemotherapy (CT) regimen.

Abstract Background Rituximab is widely used as a key component of immunochemotherapy to treat B-cell non-Hodgkin lymphoma (B-NHL). However, infusion-related reactions (IRRs) during drug administration are occasionally severe or even life-threatening and thus remain problematic for patients and healthcare providers. Aim To minimize IRRs to rituximab in patients with various types of B-NHL. Method: We stratified patients into low- (n = 39), moderate- (n = 35), and high-risk (n = 7) groups according to the number of risk factors, specifically, an indolent histology and the presence of bulky tumors (> 10 cm). For the first rituximab cycle, the low- and moderate-risk groups underwent conventional infusion #1 (~ 4.3 h), and the high-risk group underwent long infusion (6.8 h). Patients in the low-, moderate-, and high-risk groups without IRRs in the first cycle underwent short infusion (2.3 h), conventional infusion #2 (3.5 h), and conventional infusion #1, respectively. Patients with IRRs in the first cycle received a second rituximab cycle with the same schedule as that in the first cycle. The procedure for the third cycle was at the attending physician’s discretion. Results Among 81 B-NHL patients, the incidences of IRRs in the low-, moderate-, and high-risk groups were 31%, 20%, and 57%, respectively, without any grade ≥ 3 IRRs. The overall conversion rate to short infusion in the third cycle was 54%, without any IRRs. Conclusion Our step-by-step protocol provided safe and comfortable rituximab administration for both patients and practitioners (UMIN-CTR; UMIN000032309, registered on 19th April 2018).

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R-COMP 21 (Prednisone, Cyclophosphamide, Vincristine, Myocettm and Rituximab) for Frail and Elderly Patients with Aggressive B-Cell Non-Hodgkin Lymphoma: A Pilot Study.

Blood ◽

10.1182/blood.v110.11.4442.4442 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4442-4442

Author(s):

Alessandro Isidori ◽

Felicetto Ferrara ◽

Francesco Alesiani ◽

Sonia Ronconi ◽

Massimo Catarini ◽

...

Keyword(s):

Heart Failure ◽

High Risk ◽

Elderly Patients ◽

B Cell ◽

Hodgkin Lymphoma ◽

Liposomal Doxorubicin ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Non Hodgkin Lymphoma ◽

The Impact

Abstract CHOP chemotherapy is the gold standard treatment for patients with indolent and aggressive non-Hodgkin Lymphomas. However, CHOP is frequently poorly tolerated by frail and elderly patients resulting in dose reductions and consequently lower response and cure rates compared to younger patients. The toxicity and efficacy of nonpegylated liposomal doxorubicin (Myocet™) when substituted for conventional doxorubicin in the CHOP 21 regimen (Doxorubicin, Cyclophosphamide, Vincristine, Prednisone given every 3 weeks) were evaluated in the treatment of frail elderly patients with aggressive non-Hodgkin’s lymphoma. Twenty patients (median age: 73 years, range 61–82) with diffuse large B cell non-Hodgkin lymphoma, either at diagnosis (15 patients) or relapsing (5 patients), were enrolled in the study. At baseline 14/20 (72%) patients had stage III–IV disease. All patients had one or more comorbidity. Eighteen out of 20 patients (90%) had an intermediate or high risk International Prognostic Index score. The median left ventricular ejection fraction (LVEF) before starting chemotherapy was 62% (range 43–73). A total of 111 chemotherapy cycles were administered, with a median of 6 cycles (range 1–8). Of the cycles administered, 19 (17%) were delayed by haematological toxicity. The relative dose intensity for the regimen was 83%. Toxicity was mainly haematological with grade 3 or 4 neutropenia in 16% of cycles and febrile neutropenia in 5%. However, 3/20 patients presented a grade III–IV WHO toxicity (one fatal pulmonary embolism, one congestive heart failure, one ischemic heart failure) while receiving R-COMP chemotherapy. All but one patient were evaluable for response. 13 out of 19 (68%) had a complete response and an additional 5 patients (26%) achieved a partial response. Of the evaluable patients, only 1/19 (5%) did not respond at all to chemotherapy and rapidly died due to progressive disease. With a median follow-up of 14 months (range 7–18) as of July 2007, 15/18 responding patients (83%) are alive and disease free, as well as 3/18 are alive with active disease. In conclusion, the R-COMP 21 is a very effective regimen with promising response rates in frail and elderly patients with high risk aggressive non-Hodgkin lymphoma. Further studies with a larger cohort of patients are warranted to better define the impact of non pegylated liposomal doxorubicin on overall survival of this setting of elderly and particularly frail patients.

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Prognostic impact of cytogenetic abnormalities in children and adolescents with mature B-cell non-Hodgkin lymphoma: A report from the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG)

Pediatric Blood & Cancer ◽

10.1002/pbc.25482 ◽

2015 ◽

Vol 62 (7) ◽

pp. 1294-1296 ◽

Cited By ~ 5

Author(s):

Masahiro Sekimizu ◽

Tetsuya Mori ◽

Akira Kikuchi ◽

Tetsuo Mitsui ◽

Shosuke Sunami ◽

...

Keyword(s):

B Cell ◽

Children And Adolescents ◽

Hodgkin Lymphoma ◽

Study Group ◽

Prognostic Impact ◽

Pediatric Leukemia ◽

Cytogenetic Abnormalities ◽

Non Hodgkin Lymphoma ◽

Lymphoma Study Group

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Disruption of the SUMO Pathway in a High-Risk B-Cell Non-Hodgkin Lymphoma Pedigree

Blood ◽

10.1182/blood.v126.23.2682.2682 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2682-2682

Author(s):

Cassandra Garner ◽

Martha Glenn ◽

Rosalie G Waller ◽

Venkatesh Rajamanickam ◽

Todd Darlington ◽

...

Keyword(s):

High Risk ◽

B Cell ◽

Hodgkin Lymphoma ◽

Genetic Variants ◽

Molecular Mechanisms ◽

Rare Variants ◽

Association Studies ◽

Genome Wide Association Studies ◽

Non Hodgkin Lymphoma ◽

Sumo Pathway

Abstract Taken together, B-cell lymphoproliferative disorders (lymphoma, multiple myeloma and leukemia) are the fourth most common form of cancer. Chronic Lymphocytic Leukemia (CLL), a specific sub-type of B-cell non-Hodgkin lymphoma (NHL), is the most common adult leukemia in Western countries. Despite its prevalence, the underlying genetic mechanisms responsible for CLL remain largely unknown. The strong familial clustering seen in CLL suggests that genetic variants contributing to its pathogenesis may be inherited. Our lab is dedicated to identifying inherited genetic risk variants associated with hematological malignancies with a specific focus on CLL. We hypothesize that there are multiple germline genetic variants (both common and rare) involved in risk of CLL. In order to identify rare variants, our lab uses the Utah Population Database (UPDB) to identify extended high-risk pedigrees with statistical excess of familial CLL. We then use next generation sequencing to identify genetic variants segregating in these high-risk pedigrees. This powerful study design for identifying rare variants and has previously been proven successful for identifying variants associated with other cancers. We have performed whole-exome sequencing in one particularly high-risk pedigree containing 3 CLL cases and a mantle cell lymphoma case within 2 generations. We have identified variants in multiple genes associated with the SUMO pathway. We find rare variants in RANBP2, SP100, PML, IL1RL2 (paralog of IL1R) and CREBRF (transcriptional regulation through RNA pol II) that are shared by all NHL cases in this pedigree. Other genes in this pathway have been identified by previous CLL genome wide association studies, specifically FAS, TNF and SUMO1. Furthermore, a strong role has been previously suggested for the SUMO pathway in cancer cell survival and tumor progression, lending support to the potential role of this pathway in NHL risk. We are currently validating our sequence findings and determining the prevalence of these variants in other NHL cases included in the UPDB. Our high-risk pedigree findings are supportive that disruption of the SUMO pathway contributes to pathogenesis of NHL. Identification of the specific variants involved will increase our understanding of the molecular mechanisms contributing to NHL and has the potential to provide genetic markers that can be used for diagnosis and new avenues for treatment of these diseases. Disclosures No relevant conflicts of interest to declare.

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