R-CHOP intensification with mid-cycle methotrexate and consolidating AraC/TT with BCNU/aHSCT in primary aggressive lymphoma with CNS involvement

J Cancer Res Clin Oncol. 2022 Jan;148(1):205-214. doi: 10.1007/s00432-021-03663-x. Epub 2021 Jun 3.

Abstract

Purpose: Patients suffering from aggressive systemic peripheral lymphoma with primary central nervous system involvement (PCL) are a rare and sparsely investigated population. Recommended treatment regimens include a combination of intrathecal and systemic chemotherapy as well as whole brain radiotherapy while offering relatively poor survival.

Methods: We conducted a single-center retrospective study that analyzed safety and outcome of 4 + 4 cycles Rituximab (R)-CHOP and R-high-dose Methotrexate (HD-MTX) for newly diagnosed, transplant-eligible patients ("Ping-Pong"), followed by Cytarabine (AraC)/Thiotepa (TT), BCNU/TT, and autologous hematologic stem cell transplantation (aHSCT). We retrospectively analyzed a set of 16 patients with high-intermediate or high-risk IPI status.

Results: Overall response rate to Ping-Pong was 100% measured by CT/MRI, including 93.75% complete remissions after BCNU/TT followed by PBSCT. One patient failed to qualify for high-dose chemotherapy due to progression when receiving Cytarabine/TT. All patients experienced grade III adverse events, 3 of them a grade IV adverse event. Estimated progression-free survival is 93.75% after a 4.8-year follow-up currently.

Conclusion: Our study suggests high effectivity of R-CHOP with mid-cycle MTX with aHSCT consolidation towards acceptable OS results in this challenging patient population.

Keywords: HD; Lymphoma; MTX; R-CHOP.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carmustine / therapeutic use
  • Central Nervous System Neoplasms / drug therapy*
  • Cyclophosphamide / adverse effects
  • Cyclophosphamide / therapeutic use
  • Cytarabine / therapeutic use
  • Doxorubicin / adverse effects
  • Doxorubicin / therapeutic use
  • Female
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Lymphoma, Large B-Cell, Diffuse / drug therapy*
  • Male
  • Methotrexate / therapeutic use*
  • Middle Aged
  • Prednisone / adverse effects
  • Prednisone / therapeutic use
  • Progression-Free Survival
  • Retrospective Studies
  • Rituximab / therapeutic use*
  • Vincristine / adverse effects
  • Vincristine / therapeutic use

Substances

  • Cytarabine
  • Rituximab
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Carmustine
  • Prednisone
  • Methotrexate

Supplementary concepts

  • CHOP protocol