Mantle cell lymphoma: clinical features, treatment and prognosis of 94 patients

Oinonen, R.; Franssila, Kaarle; Teerenhovi, Lasse; Lappalainen, Kimmo; Elonen, Erkki

doi:10.1016/s0959-8049(97)10056-9

Cited by 62 publications

(38 citation statements)

References 27 publications

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“…[15][16][17][18] Early studies found that leukemic involvement was associated with aggressive disease and a poor prognosis; [13][14][15][16][17][18][19] however, a growing body of research has identified patients with an indolent form of MCL with relatively long survival even without therapy. [4][5]7,[9][10] Features that may identify these patients include non-nodal disease and a lack of clinical symptoms.…”

Section: Discussionmentioning

confidence: 99%

Indolent mantle cell leukemia: a clinicopathological variant characterized by isolated lymphocytosis, interstitial bone marrow involvement, kappa light chain restriction, and good prognosis

Ondrejka¹,

Lai²,

Smith³

et al. 2011

Haematologica

165

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BackgroundCases of mantle cell lymphoma with indolent behavior have been reported, but are poorly identified by current clinical risk models. Early studies found peripheral blood involvement to be an adverse prognostic factor; however, cases of a seemingly indolent variant of mantle cell lymphoma, characterized by peripheral blood involvement and minimal nodal disease, have been incompletely described, particularly with regard to bone marrow findings. We report a series of leukemic phase mantle cell lymphomas with a non-progressive or slowly progressive course. Design and MethodsCases presenting with mantle cell lymphoma limited to the peripheral blood/bone marrow from 2000-2010 were identified. Diagnoses were established by morphology, flow cytometric analysis and requisite evidence of IGH-CCND1@ by fluorescence in-situ hybridization or t(11;14)(q13;q32) by cytogenetics. Patients with lymphadenopathy, splenomegaly and gastrointestinal symptomatology were excluded. ResultsPatients (n=8, median age 60.5 years) were asymptomatic with mild lymphocytosis (8.7¥10 9 /L; range, 4.5-14.2¥10 9 /L) and cytology typical of mantle cell lymphoma. Flow cytometric analysis showed that all expressed CD5, CD19, CD20, variable CD23, and a striking kappa immunoglobulin light chain restriction (7/8 cases). Bone marrow biopsy at diagnosis showed interstitial single or small lymphoid aggregates with similar patterns of CD20 and cyclin D1 immunostaining which were not readily discernable by hematoxylin and eosin stain. SOX11 was negative (4/5) or only weakly expressed (1/5). The median follow-up was 27 months (range, 5-109 months) and all patients, but one, are alive with no clinical evidence of disease. The prevalence of indolent mantle cell lymphoma presenting only with lymphocytosis, among all mantle cell lymphomas diagnosed during the same period, was 3%. ConclusionsLeukemic mantle cell lymphoma limited to blood and bone marrow is an indolent variant characterized by mild-moderate lymphocytosis, interstitial low-level bone marrow involvement, simple karyotype, kappa light chain expression, cyclin D1 expression with lack of SOX11, and slow or absent clinical progression. Some cases may represent a mantle cell lymphoma counterpart to chronic lymphocytic leukemia -phenotype monoclonal B-cell lymphocytosis. Recognition of this variant could inform treatment decisions and possibly avoid unnecessary treatment.

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Section: Discussionmentioning

confidence: 99%

Indolent mantle cell leukemia: a clinicopathological variant characterized by isolated lymphocytosis, interstitial bone marrow involvement, kappa light chain restriction, and good prognosis

Ondrejka¹,

Lai²,

Smith³

et al. 2011

Haematologica

165

View full text Add to dashboard Cite

show abstract

“…[2][3][4] Although treatment with conventional chemotherapy results in an overall response of 60% to 80%, the majority of patients relapse and succumb to MCL. 5 The addition of the anti-CD20 antibody rituximab to first line therapy led to improved complete remission rates, but did not prolong progression-free and overall survival.…”

Section: Introductionmentioning

confidence: 99%

Direct and immune-mediated cytotoxicity of interleukin-21 contributes to antitumor effects in mantle cell lymphoma

Bhatt

Matthews

Parvin

et al. 2015

Blood

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• IL-21 activates IL-21R-dependent singling to mediate direct cytotoxicity of MCL cells.• Indirect effects of IL-21 on immune effector cells also contribute to antitumor effects against MCL.Mantle cell lymphoma (MCL) is a distinct subtype of non-Hodgkin lymphoma characterized by overexpression of cyclin D1 in 95% of patients. MCL patients experience frequent relapses resulting in median survival of 3 to 5 years, requiring more efficient therapeutic regimens. Interleukin (IL)-21, a member of the IL-2 cytokine family, possesses potent antitumor activity against a variety of cancers not expressing the IL-21 receptor (IL-21R) through immune activation. Previously, we established that IL-21 exerts direct cytotoxicity on IL-21R-expressing diffuse large B-cell lymphoma cells. Herein, we demonstrate that IL-21 possesses potent cytotoxicity against MCL cell lines and primary tumors. We identify that IL-21-induced direct cytotoxicity is mediated through signal transducer and activator of transcription 3-dependent cMyc upregulation, resulting in activation of Bax and inhibition of Bcl-2 and Bcl-X L . IL-21-mediated cMyc upregulation is only observed in IL-21-sensitive cells. Further, we demonstrate that IL-21 leads to natural killer (NK)-cell-dependent lysis of MCL cell lines that were resistant to direct cytotoxicity. In vivo treatment with IL-21 results in complete FC-muMCL1 tumor regression in syngeneic mice via NK-and T-cell-dependent mechanisms. Together, these data indicate that IL-21 has potent antitumor activity against MCL cells via direct cytotoxic and indirect, immune-mediated effects. (Blood. 2015;126(13):1555-1564

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“…1 Other extranodal sites like the gastrointestinal tract are often involved. 2 In addition to a characteristic immunophenotype, the hallmark chromosomal translocation t (11:14) leading to aberrant expression of cyclin D1 can be found in most cases. 3 The importance of an effective induction regimen containing both cytarabine and rituximab has gained support based on results from phase 2 and 3 trials.…”

Section: Introductionmentioning

confidence: 99%

Nordic MCL3 study: 90Y-ibritumomab-tiuxetan added to BEAM/C in non-CR patients before transplant in mantle cell lymphoma

Kolstad

Laurell

Jerkeman

et al. 2014

Blood

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Y-ibritumomab-tiuxetan (Zevalin) to the highdose regimen. One hundred sixty untreated, stage II-IV mantle cell lymphoma patients <66 years received rituximab (R)-maxi-CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone) alternating with R-high-dose cytarabine (6 cycles total), followed by high-dose BEAM/C (bis-chloroethylnitrosourea, etoposide, cytarabine, and melphalan or cyclophosphamide) and autologous stem cell transplantation from 2005 to 2009. Zevalin (0.4 mCi/kg) was given to responders not in CR before transplant. Overall response rate pretransplant was 97%. The outcome did not differ from that of the historic control: the MCL2 trial with similar treatment except for Zevalin. Overall survival (OS), eventfree survival (EFS), and progression-free survival (PFS) at 4 years were 78%, 62%, and 71%, respectively. For responding non-CR patients who received Zevalin, duration of response was shorter than for the CR group. Inferior PFS, EFS, and OS were predicted by positron emission tomography (PET) positivity pretransplant and detectable minimal residual disease (MRD) after transplant. In conclusion, positive PET and MRD were strong predictors of outcome. Intensification with Zevalin may be too late to improve the outcome of patients not in CR before transplant. This trial was registered at www.clinicaltrials.gov as

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Mantle cell lymphoma: clinical features, treatment and prognosis of 94 patients

Cited by 62 publications

References 27 publications

Indolent mantle cell leukemia: a clinicopathological variant characterized by isolated lymphocytosis, interstitial bone marrow involvement, kappa light chain restriction, and good prognosis

Indolent mantle cell leukemia: a clinicopathological variant characterized by isolated lymphocytosis, interstitial bone marrow involvement, kappa light chain restriction, and good prognosis

Direct and immune-mediated cytotoxicity of interleukin-21 contributes to antitumor effects in mantle cell lymphoma

Nordic MCL3 study: 90Y-ibritumomab-tiuxetan added to BEAM/C in non-CR patients before transplant in mantle cell lymphoma

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