title: Recombinant human erythropoietin for the treatment of the anaemia associated with autologous bone marrow transplantation.
abstract: Patients with solid tumours undergoing high-dose chemotherapy with autologous bone marrow transplantation use an average of 10 units of packed red blood cells (PRBC) while awaiting haemopoietic reconstitution. They are also known to have inappropriately low endogenous erythropoietin levels for their degree of anaemia. This pilot study was designed to determine the effects of recombinant human erythropoietin (rHuEPO) on erythroid recovery and PRBC transfusion requirements. Ten patients received high-dose chemotherapy (days -7 to -3), bone marrow reinfusion (day 0), and then rHuEPO (day 1 onward). RHuEPO (200 units/kg intravenous bolus daily), along with iron supplementation, was administered for 28 d or until a haematocrit (Hct) of 35% (independent of transfusions) was reached, whichever occurred first. PRBCs were routinely given for Hct < or = 25% and platelets for counts < 20,000/microliters. Eight (80%) patients developed a brisk reticulocytosis (median peak reticulocyte count 0.32 x 10(9)/l) and a haematocrit > or = 30% independent of red blood cell transfusions within 32 d of receiving marrow, as compared to 20/37 (54%) similarly treated controls. An unexpected finding was the more rapid engraftment in myeloid and platelet lineages in a subset of rHuEPO-treated patients. Quick return of red blood cells (17 v 33 d) (P = 0.0001), platelets (14 v 19 d) (P = 0.04), and neutrophils (13 v 25 d) (P = 0.01) (with circulating myeloblasts and early myeloid forms) characterized recovery from an ifosfamide-based intensification with rHuEPO support. Similar trilineage enhancement of haemopoiesis did not occur with the possibly more myeloablative cyclophosphamide-based regimens. Despite the enhancement by rHuEPO on reticulocytosis, there was no significant decrease in PRBC transfusion requirements. RHuEPO proved to be a well-tolerated agent in enhancing reticulocytosis following high-dose chemotherapy. Further study to elucidate the activity of erythropoietin on both erythroid and non-erythroid growth and maturation appears warranted.
authors.affiliation: Department of Medicine, Dana-Farber Cancer Institute, Boston, Mass 02115.
authors.forename: L J
authors.initials: LJ
authors.lastname: Ayash
authors.forename: A
authors.initials: A
authors.lastname: Elias
authors.forename: M
authors.initials: M
authors.lastname: Hunt
authors.forename: G
authors.initials: G
authors.lastname: Demetri
authors.forename: C
authors.initials: C
authors.lastname: Wheeler
authors.forename: I
authors.initials: I
authors.lastname: Tepler
authors.forename: G
authors.initials: G
authors.lastname: Schwartz
authors.forename: R
authors.initials: R
authors.lastname: Mazanet
authors.forename: E
authors.initials: E
authors.lastname: Reich
authors.forename: M
authors.initials: M
authors.lastname: McCauley
mesh_terms: D000328:Adult; D000740:Anemia / Q000139:chemically induced / Q000628:therapy*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D016913:Blood Component Transfusion; D016026:Bone Marrow Transplantation; D003131:Combined Modality Therapy; D004921:Erythropoietin / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007501:Iron / Q000097:blood; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000628:therapy*; D010865:Pilot Projects; D011994:Recombinant Proteins / Q000627:therapeutic use; D017701:Reticulocyte Count
chemical_list: D011994:Recombinant Proteins; D004921:Erythropoietin; D007501:Iron