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Phase II study of bryostatin 1 and vincristine for aggressive non‐Hodgkin lymphoma relapsing after an autologous stem cell transplant
Author(s) -
Barr Paul M.,
Lazarus Hillard M.,
Cooper Brenda W.,
Schluchter Mark D.,
Panneerselvam Ashok,
Jacobberger James W.,
Hsu Jack W.,
Janakiraman Nalini,
Simic Aleksandra,
Dowlati Afshin,
Remick Scot C.
Publication year - 2009
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.21449
Subject(s) - vincristine , medicine , bryostatin 1 , lymphoma , flow cytometry , stem cell , oncology , immunology , gastroenterology , cancer research , chemotherapy , biology , cyclophosphamide , receptor , activator (genetics) , genetics
Bryostatin 1, isolated from a marine bryozoan, enhances the efficacy of cytotoxic agents through modulation of the protein kinase C pathway and is active in combination with vincristine for diffuse large B‐cell lymphoma. Further, the apoptotic frequency of peripheral blood T lymphocytes as determined by flow cytometry may predict which patients will respond to this combination. We tested the efficacy and safety of bryostatin 1 50 μg/m 2 given over 24 hr and vincristine 1.4 mg/m 2 on days 1 and 15 every 28 days in aggressive B‐cell non‐Hodgkin lymphoma (NHL) relapsing after autologous stem cell transplantation. End points included tumor response, toxicity, and survival. Responses were correlated with an increase in apoptotic frequency of CD5+ cells by flow cytometry using annexin V staining. Fourteen patients were enrolled with 13 being evaluable for a response. The overall response rate was 31% with two patients achieving a complete response. The most common toxicities were Grade 3 lymphopenia (seven patients), Grade 3 to 4 neutropenia (two patients), and Grade 3 hypophosphatemia (two patients). Median progression‐free and overall survivals for all patients were 5.7 and 21.4 months, respectively. One patient demonstrated an increase in T‐cell apoptotic frequency, also achieving a complete response. Bryostatin 1 and vincristine have efficacy in select patients with aggressive NHL. Future investigations of agents targeting the protein kinase C pathway may benefit from early response assessment using flow cytometry to evaluate T‐cell apoptosis. Am. J. Hematol., 2009. © 2009 Wiley‐Liss, Inc.