Treatment of splenic marginal zone lymphoma of the CNS with high-dose therapy and allogeneic stem cell transplantation

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Abstract

Therapy of indolent lymphomas with involvement of the central nervous system (CNS) has not been standardized so far. A 42-year old male patient presented with neurological signs because of leukemic splenic marginal zone lymphoma (SMZL) manifested in bone marrow, lymph nodes and CNS. Due to the aggressiveness of the disease and the young age of the patient, an intensive immunochemotherapy followed by high-dose therapy with busulfan, thiotepa and fludarabine and subsequent unrelated allogeneic stem cell transplantation (alloSCT) was performed. The haemopoietic stem cells engrafted in time and the patient is doing well (ECOG 0) without evidence for active lymphoma three years after transplantation. Highly sensitive tests by specific quantitative real-time polymerase chain reaction for presence of lymphoma cells in blood and bone marrow indicated also a molecular remission. The reported case shows the feasibility of high-dose therapy and allogeneic stem cell transplantation in high-risk patients with CNS-involvement of indolent non-Hodgkin’s lymphoma. In addition, the case supports the hypothesis that the graft-versus lymphoma effect after alloSCT is also active within the CNS.

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Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients.

G Brehm, W Wilmanns, E. Holler … (1990)

Three patients with hematologic relapse after bone marrow transplantation for chronic myelogenous leukemia were treated with interferon alpha and transfusion of viable donor buffy coat. All had complete hematologic and cytogenetic remission, which persisted 32 to 91 weeks after treatment. In two patients graft-versus-host disease developed and was treated by immunosuppression. These results are an example of adoptive immunotherapy without cytoreductive chemotherapy or radiotherapy in human chimeras.

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Splenic marginal zone lymphoma: a prognostic model for clinical use.

Emilio Iannitto, Sonia A. Tucci, N. COLOMBO … (2006)

The Integruppo Italiano Linfomi (IIL) carried out a study to assess the outcomes of splenic marginal zone lymphoma and to identify prognostic factors in 309 patients. The 5-year cause-specific survival (CSS) rate was 76%. In univariate analysis, the parameters predictive of shorter CSS were hemoglobin levels below 12 g/dL (P < .001), albumin levels below 3.5 g/dL (P = .001), International Prognostic Index (IPI) scores of 2 to 3 (P < .001), lactate dehydrogenase (LDH) levels above normal (P < .001), age older than 60 years (P = .01), platelet counts below 100,000/microL (P = .04), HbsAg-positivity (P = .01), and no splenectomy at diagnosis (P = .006). Values that maintained a negative influence on CSS in multivariate analysis were hemoglobin level less than 12 g/dL, LDH level greater than normal, and albumin level less than 3.5 g/dL. Using these 3 variables, we grouped patients into 3 prognostic categories: low-risk group (41%) with no adverse factors, intermediate-risk group (34%) with one adverse factor, and high-risk group (25%) with 2 or 3 adverse factors. The 5-year CSS rate was 88% for the low-risk group, 73% for the intermediate-risk group, and 50% for the high-risk group. The cause-specific mortality rate (x 1000 person-years) was 20 for the low-risk group, 47 for the intermediate-risk group, and 174 for the high-risk group. This latter group accounted for 54% of all lymphoma-related deaths. In conclusion, with the use of readily available factors, this prognostic index may be an effective tool for evaluating the need for treatment and the intensity of therapy in an individual patient.

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Cytogenetic aberrations and their prognostic value in a series of 330 splenic marginal zone B-cell lymphomas: a multicenter study of the Splenic B-Cell Lymphoma Group.

Lourdes Florensa, Iwona Wlodarska, Marta Salido … (2010)

We conducted a retrospective collaborative study to cytogenetically characterize splenic marginal zone lymphoma (SMZL) and ascertain the prognostic value of chromosomal aberrations. Of 330 cases, 72% displayed an aberrant karyotype, 53% were complex, and 29% had a single aberration. The predominant aberrations were gains of 3/3q and 12q, deletions of 7q and 6q and translocations involving 8q/1q/14q. CD5 expression was detected in 39 of 158 cases (25%). The cytogenetic makeup of the CD5(+) group differed significantly from that of the CD5(-) group. Cases with unmutated IGHV were significantly associated with deletions of 7q and TP53. A strong association was noted between usage of the IGVH1-2 and deletion 7q, 14q alterations, and abnormal karyotype. On univariate analysis, patients with more than or equal to 2 aberrations, 14q alterations, and TP53 deletions had the shortest survival; 7q deletion did not affect survival. On multivariate analysis, cytogenetic aberrations did not retain prognostic significance; the parameters negatively affecting survival were hemoglobin and age. In conclusion, the cytogenetic profile of SMZL is distinct from other B-cell lymphomas. Complexity of the karyotype, 14q aberrations, and TP53 deletions are poor prognostic indicators and may be considered together with other clinicobiologic parameters to ascertain the prognosis of SMZL.

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Author and article information

Journal

Journal ID (nlm-ta): Exp Hematol Oncol

Journal ID (iso-abbrev): Exp Hematol Oncol

Title: Experimental Hematology & Oncology

Publisher: BioMed Central

ISSN (Electronic): 2162-3619

Publication date Collection: 2012

Publication date (Electronic): 16 October 2012

Volume: 1

Page: 32

Affiliations

[1 ]Internal Medicine C (Hematology and Oncology, Palliative Care, Transplant Centre), University Hospital Greifswald, Ernst-Moritz-Arndt-University, Greifswald, Germany

[2 ]Institute for Radiology, University Hospital Greifswald, Ernst-Moritz-Arndt-University, Greifswald, Germany

[3 ]Department of Neuropathology, Institute for Pathology, University Hospital Greifswald, Ernst-Moritz-Arndt-University, Greifswald, Germany

[4 ]Medizinische Klinik C (Hämatologie und Onkologie, Transplantationszentrum), Ernst-Moritz-Arndt-Universität Greifswald, Ferdinand-Sauerbruch-Straße, Greifswald, 17475, Germany

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Publisher ID: 2162-3619-1-32

DOI: 10.1186/2162-3619-1-32

PMC ID: 3515347

PubMed ID: 23210733

SO-VID: 8c311cfc-7d17-419f-aa75-cae419e41aa4

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This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Treatment of splenic marginal zone lymphoma of the CNS with high-dose therapy and allogeneic stem cell transplantation

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Most cited references 22

Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients.

Splenic marginal zone lymphoma: a prognostic model for clinical use.

Cytogenetic aberrations and their prognostic value in a series of 330 splenic marginal zone B-cell lymphomas: a multicenter study of the Splenic B-Cell Lymphoma Group.

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