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Two Cases of Cerebral Involvement in Malignant Lymphoma (CD20+) That Responded to Combination Therapy with Rituximab and Cladribine.

Jo T, Matsuo M, Horio K, Tomonaga M - Case Rep Oncol (2012)

Bottom Line: Furthermore, high-dose methotrexate in combination with whole-brain radiotherapy is not always effective, and high rates of neurotoxicity are often observed, particularly in the elderly.In our hospital, cladribine, a purine analogue with a cytocidal effect on resting malignant cells (G0/G1 phase of the cell cycle), has been used in combination with rituximab, which exhibits antitumor effects on nodal and extranodal lesions of relapsed and/or refractory B cell lymphomas, particularly cerebral lesions.The outcomes of these cases suggest that cladribine plus rituximab combination therapy with whole-brain radiotherapy may be very useful as salvage therapy for secondary central nervous system lymphoma and as initial therapy for primary central nervous system lymphoma.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology, Japanese Red Cross Society Nagasaki Genbaku Hospital, Nagasaki, Japan.

ABSTRACT
Cerebral involvement frequently occurs in association with progression or relapse of malignant lymphoma. Chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone, the standard chemotherapy for malignant lymphoma, is an ineffective treatment for cerebral involvement because these drugs cannot cross the blood-brain barrier. Therefore, various alternative strategies have been attempted. Although high-dose methotrexate combined with whole-brain radiotherapy is widely used to treat primary central nervous system lymphoma, there is no standard therapy to treat cerebral involvement in malignant lymphoma. Furthermore, high-dose methotrexate in combination with whole-brain radiotherapy is not always effective, and high rates of neurotoxicity are often observed, particularly in the elderly. To expand the therapeutic options for central nervous system involvement in recent years, systemic chemotherapies, including rituximab, high-dose methotrexate, and other agents that act during the S, G2, and M phases of the cell cycle, have been attempted. In our hospital, cladribine, a purine analogue with a cytocidal effect on resting malignant cells (G0/G1 phase of the cell cycle), has been used in combination with rituximab, which exhibits antitumor effects on nodal and extranodal lesions of relapsed and/or refractory B cell lymphomas, particularly cerebral lesions. Here, we report 2 representative cases of patients who were treated with cladribine plus rituximab and survived for 30 months (died of sepsis) and 52 months (still alive), respectively. The outcomes of these cases suggest that cladribine plus rituximab combination therapy with whole-brain radiotherapy may be very useful as salvage therapy for secondary central nervous system lymphoma and as initial therapy for primary central nervous system lymphoma.

No MeSH data available.


Related in: MedlinePlus

CT images of case 1. Multiple high-density areas surrounded by low-density areas (arrows) were observed prior to RC combination therapy (a–d). An effect was apparent after 6 cycles of RC combination therapy (e–h).
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Figure 1: CT images of case 1. Multiple high-density areas surrounded by low-density areas (arrows) were observed prior to RC combination therapy (a–d). An effect was apparent after 6 cycles of RC combination therapy (e–h).

Mentions: Also in April 2003, the patient underwent total gastrectomy, splenectomy, and cholecystectomy, and was diagnosed with stage IV intravascular large B-cell lymphoma (CD5–, CD10–, CD20+, CD45RO–, bcl2+, bcl6–, EBER(ISH)–). After 4 cycles of rituximab, pirarubicin, cyclophosphamide, vincristine, and prednisolone (R-THP-COP) therapy, the nodal lesions were generally reduced, which led to the patient's discharge in July 2003. He was given 2 additional cycles of R-THP-COP; however, in September 2003, he required rehospitalization after a brain CT revealed many central nervous system lesions. High-dose MTX combined with WBRT (total dose of 36 Gy) was immediately administered, but in vain. Given his advanced age and weakness, high-dose cytosine arabinoside therapy was not considered. Instead, he received 2 cycles of RC combination therapy (375 mg/m2 rituximab intravenously on day 1 and 0.1 mg/kg cladribine intravenously once a day on days 2–6), and most of his intracranial lesions disappeared by November 2003. He was ambulatory on discharge and had no neurological symptoms. He completed another 4 cycles of RC combination therapy by April 2004 (fig. 1), and complete response (Response Evaluation Criteria in Solid Tumors (RECIST) classification) was maintained until March 2006. After 6 cycles of RC combination therapy, pancytopenia was observed in May 2004. Chemotherapy-related myelodysplastic syndrome (MDS) was suspected by laboratory examination, including bone marrow aspiration. In January 2006, he developed a high fever and was urgently admitted to our department where he was treated for recurrent Gram-positive and Gram-negative sepsis. In March 2006, he was transferred to another hospital for hospice care because he wished no further aggressive treatment. No neurotoxicity due to chemotherapy and WBRT was observed during the entire course of treatment.


Two Cases of Cerebral Involvement in Malignant Lymphoma (CD20+) That Responded to Combination Therapy with Rituximab and Cladribine.

Jo T, Matsuo M, Horio K, Tomonaga M - Case Rep Oncol (2012)

CT images of case 1. Multiple high-density areas surrounded by low-density areas (arrows) were observed prior to RC combination therapy (a–d). An effect was apparent after 6 cycles of RC combination therapy (e–h).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3376337&req=5

Figure 1: CT images of case 1. Multiple high-density areas surrounded by low-density areas (arrows) were observed prior to RC combination therapy (a–d). An effect was apparent after 6 cycles of RC combination therapy (e–h).
Mentions: Also in April 2003, the patient underwent total gastrectomy, splenectomy, and cholecystectomy, and was diagnosed with stage IV intravascular large B-cell lymphoma (CD5–, CD10–, CD20+, CD45RO–, bcl2+, bcl6–, EBER(ISH)–). After 4 cycles of rituximab, pirarubicin, cyclophosphamide, vincristine, and prednisolone (R-THP-COP) therapy, the nodal lesions were generally reduced, which led to the patient's discharge in July 2003. He was given 2 additional cycles of R-THP-COP; however, in September 2003, he required rehospitalization after a brain CT revealed many central nervous system lesions. High-dose MTX combined with WBRT (total dose of 36 Gy) was immediately administered, but in vain. Given his advanced age and weakness, high-dose cytosine arabinoside therapy was not considered. Instead, he received 2 cycles of RC combination therapy (375 mg/m2 rituximab intravenously on day 1 and 0.1 mg/kg cladribine intravenously once a day on days 2–6), and most of his intracranial lesions disappeared by November 2003. He was ambulatory on discharge and had no neurological symptoms. He completed another 4 cycles of RC combination therapy by April 2004 (fig. 1), and complete response (Response Evaluation Criteria in Solid Tumors (RECIST) classification) was maintained until March 2006. After 6 cycles of RC combination therapy, pancytopenia was observed in May 2004. Chemotherapy-related myelodysplastic syndrome (MDS) was suspected by laboratory examination, including bone marrow aspiration. In January 2006, he developed a high fever and was urgently admitted to our department where he was treated for recurrent Gram-positive and Gram-negative sepsis. In March 2006, he was transferred to another hospital for hospice care because he wished no further aggressive treatment. No neurotoxicity due to chemotherapy and WBRT was observed during the entire course of treatment.

Bottom Line: Furthermore, high-dose methotrexate in combination with whole-brain radiotherapy is not always effective, and high rates of neurotoxicity are often observed, particularly in the elderly.In our hospital, cladribine, a purine analogue with a cytocidal effect on resting malignant cells (G0/G1 phase of the cell cycle), has been used in combination with rituximab, which exhibits antitumor effects on nodal and extranodal lesions of relapsed and/or refractory B cell lymphomas, particularly cerebral lesions.The outcomes of these cases suggest that cladribine plus rituximab combination therapy with whole-brain radiotherapy may be very useful as salvage therapy for secondary central nervous system lymphoma and as initial therapy for primary central nervous system lymphoma.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology, Japanese Red Cross Society Nagasaki Genbaku Hospital, Nagasaki, Japan.

ABSTRACT
Cerebral involvement frequently occurs in association with progression or relapse of malignant lymphoma. Chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone, the standard chemotherapy for malignant lymphoma, is an ineffective treatment for cerebral involvement because these drugs cannot cross the blood-brain barrier. Therefore, various alternative strategies have been attempted. Although high-dose methotrexate combined with whole-brain radiotherapy is widely used to treat primary central nervous system lymphoma, there is no standard therapy to treat cerebral involvement in malignant lymphoma. Furthermore, high-dose methotrexate in combination with whole-brain radiotherapy is not always effective, and high rates of neurotoxicity are often observed, particularly in the elderly. To expand the therapeutic options for central nervous system involvement in recent years, systemic chemotherapies, including rituximab, high-dose methotrexate, and other agents that act during the S, G2, and M phases of the cell cycle, have been attempted. In our hospital, cladribine, a purine analogue with a cytocidal effect on resting malignant cells (G0/G1 phase of the cell cycle), has been used in combination with rituximab, which exhibits antitumor effects on nodal and extranodal lesions of relapsed and/or refractory B cell lymphomas, particularly cerebral lesions. Here, we report 2 representative cases of patients who were treated with cladribine plus rituximab and survived for 30 months (died of sepsis) and 52 months (still alive), respectively. The outcomes of these cases suggest that cladribine plus rituximab combination therapy with whole-brain radiotherapy may be very useful as salvage therapy for secondary central nervous system lymphoma and as initial therapy for primary central nervous system lymphoma.

No MeSH data available.


Related in: MedlinePlus