Salvage chemotherapy for refractory and relapsed posttransplant lymphoproliferative disorders (PTLD) after treatment with single-agent rituximab.
BACKGROUND
Single-agent rituximab has demonstrated encouraging efficacy and tolerability in posttransplant lymphoproliferative disorders (PTLDs) failing to respond to immunosuppression reduction (IR). This retrospective analysis was undertaken to determine the efficacy and safety of salvage therapy in recipients of solid organ transplants with progression of PTLD after rituximab first-line therapy.


METHODS
Eleven patients who had received IR and single-agent rituximab were analyzed. Of these, 10 had received CHOP salvage chemotherapy. One patient with limited disease received tumor irradiation and further IR. Most patients (73%) had late PTLD (median onset of disease 145 months posttransplant), and most (83%) had monomorphic histology; 36% had EBV-association.


RESULTS
IR and irradiation therapy re-induced complete remission (CR) and allowed long-term disease control in a patient with polymorphic PTLD relapse. CHOP therapy achieved CR in five (50%) and partial remission (PR) in two (20%) patients. Four of five (80%) patients achieving CR remained in CR at a median follow-up of 44.2 months. Of the patients achieving PR, one is currently alive, and the second died from transplant rejection after converting to CR after consolidative chemotherapy. Patients with stable disease (two) and progressive disease (one) have died from PTLD. There was one possible CHOP-associated death (acute cardiac event) and two patients had to be switched to less-toxic monotherapies. Median overall survival was 46.5 months (95% confidence interval: 23.6-49.1 months).


CONCLUSIONS
CHOP salvage therapy achieved a favorable overall response rate of 70% in this setting, indicating that PTLD generally remains chemotherapy-sensitive after progression following first-line rituximab.
Trappe
Ralf
R
1Department of Hematology and Oncology, Charité - Universitätsmedizin Berlin, Berlin, Germany. ralf.trappe@charite.de
Riess
Hanno
H
Babel
Nina
N
Hummel
Manfred
M
Lehmkuhl
Hans
H
Jonas
Sven
S
Anagnostopoulos
Ioannis
I
Papp-Vary
Matthias
M
Reinke
Petra
P
Hetzer
Roland
R
Dörken
Bernd
B
Oertel
Stephan
S
D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology*; D016031:Liver Transplantation / Q000009:adverse effects* / Q000276:immunology*; D008232:Lymphoproliferative Disorders / Q000188:drug therapy* / Q000209:etiology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D016035:Pancreas Transplantation / Q000009:adverse effects / Q000276:immunology; D011241:Prednisone / Q000008:administration & dosage; D012008:Recurrence; D012189:Retrospective Studies; D000069283:Rituximab; D016019:Survival Analysis; D014750:Vincristine / Q000008:administration & dosage
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone