A phase II multicenter trial of high-dose sequential chemotherapy and peripheral blood stem cell transplantation as initial therapy for patients with high-risk non-Hodgkin's lymphoma.
The purpose of this study was to evaluate the safety and feasibility of front-line high-dose sequential (HDS) chemotherapy with peripheral blood stem cell (PBSC) transplantation in patients with newly diagnosed high-risk non-Hodgkin's lymphoma (NHL). Thirty-two patients with high-risk NHL (defined by the age-adjusted international index) underwent HDS chemotherapy followed by PBSC transplantation and consolidative radiotherapy. Twenty-eight patients (88%) had intermediate/high grade NHL and four patients (12%) had small noncleaved or lymphoblastic lymphoma. Twenty-four patients were classified as high-intermediate-risk (two risk factors) and eight patients were classified as high-risk (three risk factors). The five phases of HDS (see Fig. 1) consisted of Phase I (adriamycin, vincristine, and prednisone); Phase II (cyclophosphamide, filgrastim [G-CSF], and PBSC harvest); Phase III (methotrexate, leucovorin, vincristine; Phase IV (etoposide, filgrastim [G-CSF]); and Phase V (mitoxantrone, melphalan, autologous peripheral blood stem cell infusion, and filgrastim [G-CSF]). Radiation therapy was given to sites of previous bulk disease, 2400 cGy, (D + 30-100)]. Toxicity, engraftment, hospital utilization, overall survival, and relapse-free survival were evaluated. The high-dose sequential chemotherapeutic regimen was well tolerated. Treatment-related mortality was 6.25% with two deaths occurring secondary to sepsis and one death was caused by progressive disease. The major toxicity in Phase I-IV was grade 3 nausea/vomiting. The major toxicity in Phase V was grade 3 or 4 nausea/vomiting and mucositis. The median follow-up is 18.8 months (range 4-44 months). The overall survival (OS) and relapse-free survival (RFS) at 18 months for all patients were 78% (95% CI 37-90%) and 67% (95% CI 46-88%), respectively. The OS at 18 months for all patients, excluding the four patients with either small noncleaved or lymphoblastic lymphoma, was 82% (95% CI 65-98%) vs. 30% (95% CI 0-86%) (p = 0.0059). One patient in this latter group remains alive at 6 months follow-up. The RFS for all patients, excluding the four patients with either small noncleaved or lymphoblastic lymphoma, was 78% (95% CI 58-97%) vs. 0% (95% CI 0-0%) (p = 0.0004). High-dose sequential chemotherapy with initial PBSC transplantation is well tolerated and appears effective in high-risk NHL. Superior results were noted in patients with intermediate grade versus those with small noncleaved or lymphoblastic NHL.
Schenkein
D P
DP
Tupper Research Institute, New England Medical Center, Boston, MA, USA.
Roitman
D
D
Miller
K B
KB
Morelli
J
J
Stadtmauer
E
E
Pecora
A L
AL
Cassileth
P
P
Fernandez
H
H
Cooper
B W
BW
Kutteh
L
L
Lazarus
H M
HM
D000328:Adult; D003131:Combined Modality Therapy / Q000592:standards; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D000069585:Filgrastim; D005500:Follow-Up Studies; D006085:Graft Survival; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008228:Lymphoma, Non-Hodgkin / Q000401:mortality / Q000628:therapy*; D008297:Male; D008558:Melphalan; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011994:Recombinant Proteins; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use
D007166:Immunosuppressive Agents; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D000069585:Filgrastim; D008558:Melphalan; D002955:Leucovorin; D011241:Prednisone; D008727:Methotrexate