Prophylaxis of brain and spinal cord in diffuse large B- cell lymphoma (DLBCL)

Brain and spinal cord(CNS) are “sanctuary” sites, places within the body where lymphoma cells can hide out and survive chemotherapy. Testicles is another such site. There remains an open question about whether intermediate risk lymphomas, such as diffuse large cell lymphomas, that invovle organs other than lymph nodes require prophylaxis against CNS involvement alingside methotrexate, that gets well into the CNS form the blood, with follinic acid rescue. The consensus is that some such sites, such as testicular lymphoma, should get prophylaxis and some should not. European Society of Medical Oncology(ESMO) writes: “Patients with high–intermediate- and high-risk IPI, especially those with more than one extranodal site or elevated LDH are at higher risk of CNS relapse. CNS prophylaxis should be recommended in this population but intrathecal injections of methotrexate are probably not an optimal method. Whether some specific involvement sites such as paranasal sinus, upper neck or bone marrow should receive prophylaxis remains to be established. Testicular lymphoma must receive CNS prophylaxis”. The National Comprehensive Cancer Network ( guidelines for diffuse large B-cell (DLBCL) lymphoma recommend CNS prophylaxis with 4 to 8 doses of intrathecal methotrexate (MTX) and/or cytarabine for patients with aggressive lymphomas who have paranasal sinus, testicular, epidural, bone marrow, 2 extranodal site involvement, or HIV lymphomas. A recent(2012) review of the impact of CNS prophylaxis in DLBCL patients treated with modern chemotehrapy R-CHOP at a tertiary care centre over a 7-year period concluded that in the era of R-CHOP there may not be a need for CNS prophylaxis with the exception of testicular lymphoma.

There is a trial that is looking at this question: Dose Dense Chemotherapy and Rituximab for Young High Risk Diffuse Large B-Cell Lymphoma Patients (CRY-04), NCT01502982

The purpose is to test whether dose densified chemoimmunotherapy followed by central nervous system (CNS) prophylaxis for young high risk diffuse large B-cell lymphoma (DLBCL) patients is feasible and could improve time to treatment failure and reduce the risk of CNS relapses. Six courses of rituximab-cyclophosphamide-doxorubicin-etoposide-vincristine-prednison (R-CHOEP) given in two weeks intervals with the support of G-CSF is followed by one course of high dose methotrexate (HD-MTX) and high dose cytarabine (HD-Ara-C). The results will be compared to a historical Nordic study.


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