title: Autologous progenitor cell transplantation: prior exposure to stem cell-toxic drugs determines yield and engraftment of peripheral blood progenitor cell but not of bone marrow grafts.
abstract: Agents with stem cell-toxic potential are frequently used for salvage therapy of Hodgkin's disease (HD) and high-grade non-Hodgkin's lymphoma (NHL). Because many patients with relapsed or refractory lymphoma are candidates for autologous progenitor cell transplantation, possible toxic effects of salvage chemotherapy on progenitor cells must be taken into account. In a retrospective study, we have analyzed the influence of a salvage regimen containing the stem cell-toxic drugs BCNU and melphalan (Dexa-BEAM) on subsequently harvested bone marrow (BM)- and peripheral blood-derived progenitor cell grafts (PBPC) and compared it with other factors. Progenitor cells were collected from 96 patients with HD or high-grade NHL. Seventy-nine grafts were reinfused (35 PBPC and 44 BM) after high-dose chemotherapy. Compared with patients autografted with BM, hematopoietic recovery was significantly accelerated in recipients of PBPC. For PBPC, the number of Dexa-BEAM cycles ( > or = v > 1) was the predominate prognostic factor affecting colony-forming unit-granulocyte-macrophage (CFU-GM) yield (66 v 6.8 x 10(4)/kg, P = .0001), CD34+ cell yield (6.6 v 1.6 x 10(6)/kg, P = .0001), neutrophil recovery to > 0.5 x 10(9)/L (9 v. 11 days, P = .0086), platelet recovery to > 20 x 10(9)/L (10 v 15.5 days, P = .0002), and platelet count on day +100 after transplantation (190 v 107 x 10(9)/L, P = .031) using univariate analysis. Previous radiotherapy was associated with significantly lower CFU-GM and CD34+ cell yields but had no influence on engraftment. Patient age, patient sex, disease activity, or chemotherapy other than Dexa-BEAM did not have any prognostic impact. Multivariate analysis confirmed that Dexa-BEAM chemotherapy was the overriding factor adversely influencing CFU-GM yield (P < .0001), CD34+ cell yield (P < .0001), and platelet engraftment (P < .0001). BM grafts were not significantly affected by previous Dexa-BEAM chemotherapy or any other variable tested. However, prognostic factors favoring the use of BM instead of PBPC were not identified using joint regression models involving interaction terms between the graft type (PBPC or BM) and the explanatory variables investigated. We conclude that, in contrast to previous radiotherapy or other chemotherapy, exposure to salvage regimens containing stem cell-toxic drugs, such as BCNU and melphalan, is a critical factor adversely affecting yields and performance of PBPC grafts. Marrow progenitor cells appear to be less sensitive to stem cell-toxic chemotherapy. PBPC should be harvested before repeated courses of salvage chemotherapy involving stem cell-toxic drugs to preserve the favorable repopulation kinetics of PBPC in comparison with BM.
authors.affiliation: Second Department of Medicine, University of Kiel, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Dreger
authors.forename: M
authors.initials: M
authors.lastname: Klöss
authors.forename: B
authors.initials: B
authors.lastname: Petersen
authors.forename: T
authors.initials: T
authors.lastname: Haferlach
authors.forename: H
authors.initials: H
authors.lastname: Löffler
authors.forename: M
authors.initials: M
authors.lastname: Loeffler
authors.forename: N
authors.initials: N
authors.lastname: Schmitz
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D001761:Bleomycin / Q000008:administration & dosage; D001773:Blood Cells; D001853:Bone Marrow / Q000187:drug effects* / Q000528:radiation effects; D016026:Bone Marrow Transplantation; D002330:Carmustine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006037:Glyoxal / Q000008:administration & dosage; D006085:Graft Survival / Q000187:drug effects*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000528:radiation effects; D006689:Hodgkin Disease / Q000097:blood / Q000188:drug therapy / Q000628:therapy*; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000188:drug therapy / Q000628:therapy*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D008875:Middle Aged; D015999:Multivariate Analysis; D011238:Prednimustine / Q000008:administration & dosage; D011239:Prednisolone / Q000008:administration & dosage; D011241:Prednisone / Q000008:administration & dosage; D011344:Procarbazine / Q000008:administration & dosage; D011878:Radiotherapy / Q000009:adverse effects; D012189:Retrospective Studies; D016879:Salvage Therapy; D014747:Vinblastine / Q000008:administration & dosage; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D003561:Cytarabine; D001761:Bleomycin; D011344:Procarbazine; D006037:Glyoxal; D014750:Vincristine; D014747:Vinblastine; D005047:Etoposide; D003907:Dexamethasone; D004317:Doxorubicin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide; D011238:Prednimustine; D011239:Prednisolone; D008558:Melphalan; D002330:Carmustine; D007069:Ifosfamide; D011241:Prednisone