ABSTRACT
In the present study we combined interferon (IFN) and hydroxyurea (HU) treatment, intensive chemotherapy and autologous stem cell transplantation (SCT) in newly diagnosed chronic myelogenous leukemia patients aged below 56 years, not eligible for allogeneic SCT. Patients who had an HLA-identical sibling donor and no contraindication went for an allogeneic SCT (related donor, RD). After diagnosis, patients not allotransplanted received HU and IFN to keep WBC and platelet counts low. After 6 months patients with Ph-positive cells still present in the bone marrow received 1-3 courses of intensive chemotherapy. Those who became Ph-negative after IFN + HU or after 1-3 chemotherapy courses underwent autologous SCT. Some patients with poor cytogenetic response were allotransplanted with an unrelated donor (URD). IFN + HU reduced the percentage of Ph-positive metaphases in 56% of patients, and 1 patient became Ph-negative. After one or two intensive cytotherapies 86 and 88% had a Ph reduction, and 34 and 40% became Ph-negative, respectively. In patients receiving a third intensive chemotherapy 92% achieved a Ph reduction and 8% became Ph-negative. The median survival after auto-SCT (n = 46) was 7.5 years. The chance of remaining Ph-negative for up to 10 years after autologous SCT was around 20%. The overall survival for allo-SCT RD (n = 91) and URD (n = 28) was almost the same, i.e. approximately 60% at 10 years. The median survival for all 251 patients registered was 8 years (historical controls 3.5 years). The role of the treatment schedule presented in the imatinib era is discussed.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Hematopoietic Stem Cell Transplantation , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , Adolescent , Adult , Antineoplastic Agents/administration & dosage , Denmark , Female , Follow-Up Studies , Humans , Hydroxyurea/administration & dosage , Interferons/administration & dosage , Leukapheresis , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/mortality , Male , Middle Aged , Multicenter Studies as Topic , Survival Analysis , Sweden , Transplantation, Autologous , Transplantation, HomologousABSTRACT
In attempting to restore the chronic phase (CP) of chronic myelogenous leukaemia (CML), the Swedish CML group utilized an intensive chemotherapy protocol for 83 patients (aged 16-79 years) in accelerated (AP, n = 22) or blastic phase (BC, n = 61). Most patients received a combination of mitoxantrone (12 mg/m2/d) and etoposide (100 mg/m2/d) together with cytosine arabinoside (1 g/m2 b.i.d) for 4 d. Overall, 39 patients (47%) achieved a second CP (CP2)/partial remission (PR). Responding patients < 65 years were eligible for ablative chemotherapy followed by an allogeneic (SCT) or a double autologous stem cell transplant (ASCT). Seventeen of 34 responders < 65 years failed to proceed to transplantation as a result of early disease progression (n = 15) or disease-related complications (n = 2). The remaining 17 patients underwent SCT (n = 9; including four unrelated donor SCT) or ASCT (n = 8). Only one of the eight ASCT patients had a second ASCT; the remaining seven failed because of progression (n = 5) or hypoplasia (n = 2). The median duration of CP2/PR was 6 months (range 1-72 months). Five patients achieved a longer CP2/PR than CP1. The 1 year survival was 70% for SCT/ASCT patients (median survival 21 months), 50% for responding patients overall, but only 7% for non-responders (P < 0.001). Three SCT/ASCT patients are long-term survivors (65+, 66+ and 73+ months). In conclusion, approximately half of the patients achieved a CP2/PR after intensive chemotherapy, with a clear survival advantage for responders vs non-responders. Subsequent SCT/ASCT was feasible for half of the responders (< 65 years), and one individual underwent double ASCT. Novel therapeutic options for CML patients in AP/BP are needed.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Adolescent , Adult , Aged , Blast Crisis , Combined Modality Therapy , Cytarabine/administration & dosage , Etoposide/administration & dosage , Female , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/mortality , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/surgery , Male , Middle Aged , Mitoxantrone/administration & dosage , Prognosis , Remission Induction , Statistics, Nonparametric , Stem Cell Transplantation , Survival RateABSTRACT
In this national study, we have evaluated a new intensive chemotherapy protocol for adult patients with untreated acute lymphoblastic leukaemia (ALL). One hundred and fifty-three patients with median age 42 years received induction therapy with high-dose cytarabine (Ara-C), cyclophosphamide, daunorubicin, vincristine and betamethasone. A high complete remission (CR) rate (90%) was achieved in patients < 60 years compared with 70% in patients > 60 years (P = 0.004). The estimated 3 year overall survival for all patients was 29% (CI 21-36%) and the estimated continuous complete remission (CCR) at 3 years for the patients achieving CR according to the protocol was 36% (CI 27-45%). A favourable pretreatment characteristic was pre-B phenotype, especially for patients < 40 years without any high-risk factor, with an estimated CCR at 3 years of 62% (CI 41-82%). Stem cell transplantation (SCT) as post-remission therapy, mainly for high-risk patients, gave an estimated 3 year disease free survival (DFS) after SCT of 39% (CI 24-54%). No significant differences in DFS could be found between autologous, related or unrelated donor transplantation. We conclude that this intensive protocol resulted in a high CR rate combined with acceptable side-effects and a favourable CCR for patients with pre-B ALL.
