title: Low-dose total body irradiation followed by allogeneic lymphocyte infusion may induce remission in patients with refractory hematologic malignancy.
abstract: Allogeneic stem cell transplantation is curative for certain cancers, but the high doses of chemotherapy/radiotherapy lead to toxicity. Here, we treat patients with refractory cancer with 100 cGy total body irradiation (TBI) followed by infusion of nonmobilized pheresed allogeneic peripheral blood cells. Twenty-five patients, with a median age of 47 years, with refractory cancers were enrolled. Eighteen patients received sibling and 7 received unrelated cord blood cells. Donor chimerism was assessed at weeks 1, 2, 3, 4, and 8 after transplantation. Seven patients with solid tumors received a sibling transplant and 6 received a cord blood transplant; none achieved donor chimerism, but 1 treated at the higher dose level of 1 x 10(8) CD3+ cells/kg had a transient nodal response. Twelve patients with hematologic malignancies were treated; 1 received a cord blood transplant and 11 received sibling donor cells. Nine of these 11 patients achieved donor chimerism, ranging from 5% to 100%. Four patients had sustained complete remission of their cancers, including one patient with transient 5% donor chimerism. The development of chimerism correlated with hematologic malignancy (P <.001), total previous myelotoxic chemotherapy (P <.001), T-cell dose (P =.03), and graft-versus-host disease (P =.01). Tumor response correlated with donor chimerism (P =.01). Engraftment was achieved in patients with hematologic malignancies who had been heavily pretreated, suggesting the degree of immunosuppression may be a determinant of engraftment. Low-dose TBI and allogeneic lymphocyte infusion may induce remission in patients with refractory hematologic malignancy.
authors.affiliation: Cancer Center and Department of Medicine, University of Massachusetts Memorial Health Care, Worcester, MA, USA. kballen@partners.org
authors.forename: Karen K
authors.initials: KK
authors.lastname: Ballen
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Becker
authors.forename: Robert V B
authors.initials: RV
authors.lastname: Emmons
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Fitzgerald
authors.forename: Chung C
authors.initials: CC
authors.lastname: Hsieh
authors.forename: Qin
authors.initials: Q
authors.lastname: Liu
authors.forename: Christine
authors.initials: C
authors.lastname: Heyes
authors.forename: Yeteive
authors.initials: Y
authors.lastname: Clark
authors.forename: William
authors.initials: W
authors.lastname: Levy
authors.forename: Jean Francois
authors.initials: JF
authors.lastname: Lambert
authors.forename: Frank
authors.initials: F
authors.lastname: Chiafari
authors.forename: Irma
authors.initials: I
authors.lastname: Szymanski
authors.forename: Sarah
authors.initials: S
authors.lastname: Rososhansky
authors.forename: Mark A
authors.initials: MA
authors.lastname: Popovsky
authors.forename: F Marc
authors.initials: FM
authors.lastname: Stewart
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Quesenberry
mesh_terms: D000328:Adult; D000368:Aged; D005312:Fetal Blood; D006085:Graft Survival; D019337:Hematologic Neoplasms / Q000150:complications / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006801:Humans; D017710:Lymphocyte Transfusion / Q000379:methods*; D008875:Middle Aged; D011829:Radiation Dosage; D012074:Remission Induction / Q000379:methods; D016879:Salvage Therapy; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods / Q000401:mortality; D016896:Treatment Outcome; D014916:Whole-Body Irradiation / Q000009:adverse effects / Q000379:methods*