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2.
Ann Hematol ; 96(9): 1463-1470, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28725989

ABSTRACT

We evaluated clinical characteristics and outcome on imatinib of 22 patients with myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRB. Median age was 49 years (range 20-80), 91% were male. Fifteen different PDGFRB fusion genes were identified. Eosinophilia was absent in 4/19 (21%) cases and only 11/19 (58%) cases had eosinophils ≥1.5×109/L. On imatinib, 17/17 (100%) patients in chronic phase achieved complete hematologic remission after median 2 months (range 0-13)​. Complete cytogenetic remission and/or complete molecular remission by RT-PCR were achieved in 12/13 (92%) and 12/14 patients (86%) after median 10 (range 3-34) and 19 months (range 7-110), respectively. In patients with blast phase (myeloid, n = 2; lymphoid, n = 3), treatment included combinations of imatinib (n = 5), intensive chemotherapy (n = 3), and/or allogeneic stem cell transplantation (n = 3). All 3 transplanted patients (complex karyotype, n = 2) experienced early relapse. Initially, patients were treated with imatinib 400 mg/day (n = 15) or 100 mg/day (n = 7), the dose was reduced from 400 mg/day to 100 mg/day during follow-up in 9 patients. After a median treatment of 71 months (range 1-135), the 5-year survival rate was 83%; 4/22 (18%) patients died (chronic phase; n = 2; blast phase, n = 2) due to progression (n = 3) or comorbidity while in remission (n = 1). Of note, 3/4 patients had a complex karyotype. In summary, the most important characteristics of myeloid/lymphoid neoplasms with rearrangement of PDGFRB include (a) male predominance, (b) frequent lack of hypereosinophilia,


Subject(s)
Blast Crisis , Eosinophilia , Gene Rearrangement , Hematologic Neoplasms , Imatinib Mesylate/administration & dosage , Receptor, Platelet-Derived Growth Factor beta/genetics , Abnormal Karyotype , Adult , Aged , Aged, 80 and over , Blast Crisis/drug therapy , Blast Crisis/genetics , Blast Crisis/mortality , Blast Crisis/pathology , Disease-Free Survival , Eosinophilia/drug therapy , Eosinophilia/genetics , Eosinophilia/mortality , Eosinophilia/pathology , Female , Follow-Up Studies , Hematologic Neoplasms/drug therapy , Hematologic Neoplasms/genetics , Hematologic Neoplasms/mortality , Hematologic Neoplasms/pathology , Humans , Male , Middle Aged , Reverse Transcriptase Polymerase Chain Reaction , Risk Factors , Sex Factors , Survival Rate
3.
N Engl J Med ; 348(24): 2386-95, 2003 Jun 12.
Article in English | MEDLINE | ID: mdl-12802024

ABSTRACT

BACKGROUND: Faced with unsatisfactory results of treatment for advanced Hodgkin's disease, we investigated three combinations of chemotherapy. METHODS: From 1993 to 1998, 1201 eligible patients 15 to 65 years of age who had newly diagnosed Hodgkin's disease in unfavorable stage IIB or IIIA or stage IIIB or IV were randomly assigned to receive eight cycles of cyclophosphamide, vincristine, procarbazine, and prednisone alternating with doxorubicin, bleomycin, vinblastine, and dacarbazine (COPP-ABVD); bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP); or increased-dose BEACOPP, each followed by local radiotherapy when indicated. Enrollment in the COPP-ABVD group was stopped in 1996 owing to inferior results. RESULTS: For the final analysis, 1195 of 1201 patients could be evaluated: 260 in the COPP-ABVD group, 469 in the BEACOPP group, and 466 in the increased-dose BEACOPP group; the median follow-up was 72, 54, and 51 months, respectively. The rate of freedom from treatment failure at five years was 69 percent in the COPP-ABVD group, 76 percent in the BEACOPP group, and 87 percent in the increased-dose BEACOPP group (P=0.04 for the comparison of the COPP-ABVD group with the BEACOPP group and P<0.001 for the comparison of the increased-dose BEACOPP group with the COPP-ABVD group and with the BEACOPP group), and the five-year rates of overall survival were 83 percent, 88 percent, and 91 percent, respectively (P=0.16 for the comparison of the COPP-ABVD group with the BEACOPP group, P=0.06 for the comparison of the BEACOPP group with the increased-dose BEACOPP group, and P=0.002 for the comparison of the COPP-ABVD group with the increased-dose BEACOPP group). Rates of early progression were significantly lower with increased-dose BEACOPP than with COPP-ABVD or standard BEACOPP. CONCLUSIONS: Increased-dose BEACOPP resulted in better tumor control and overall survival than did COPP-ABVD.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hodgkin Disease/drug therapy , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Bleomycin/administration & dosage , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Dacarbazine/administration & dosage , Dose-Response Relationship, Drug , Doxorubicin/administration & dosage , Etoposide/administration & dosage , Female , Hodgkin Disease/mortality , Hodgkin Disease/pathology , Hodgkin Disease/radiotherapy , Humans , Leukemia/epidemiology , Male , Middle Aged , Neoplasm Staging , Neoplasms, Second Primary/epidemiology , Prednisone/administration & dosage , Procarbazine/administration & dosage , Survival Analysis , Vinblastine/administration & dosage , Vincristine/administration & dosage
4.
J Clin Oncol ; 20(2): 476-84, 2002 Jan 15.
Article in English | MEDLINE | ID: mdl-11786577

ABSTRACT

PURPOSE: To investigate whether treatment results in intermediate-stage Hodgkin's lymphoma can be improved by rapid application of non-cross-resistant drugs, the 10-drug regimen cyclophosphamide, vincristine, procarbazine, and prednisone (COPP), doxorubicin, bleomycin, and vinblastine (ABV), and ifosfamide, methotrexate, etoposide, and prednisone (IMEP), repeated every 6 weeks, was compared with conventional alternating COPP/doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) administered every 8 weeks. PATIENTS AND METHODS: From January 1988 to January 1993, 996 patients in stage I or II Hodgkin's lymphoma with at least one risk factor (massive mediastinal tumor, massive spleen involvement, extranodal disease, elevated ESR, or more than two lymph node areas involved) and all patients in stage IIIA Hodgkin's lymphoma were randomized to receive two cycles of COPP/ABVD or COPP/ABV/IMEP followed by extended-field radiotherapy. RESULTS: Both regimens produced similar rates for treatment responses (complete remission, 93% v 94%), freedom from treatment failure (80% v 79%), and overall survival (88% for both regimens) at a median follow-up time of 7 years. Most serious toxicities during chemotherapy were similar in both regimens. However, World Health Organization grade 3 and 4 leukocytopenia occurred significantly more frequently in the COPP/ABV/IMEP arm (53% v 44% of patients; P =.010). There were no differences in the number of serious infections and toxic deaths during therapy. The number of second malignancies was also the same in both arms (22 each). CONCLUSION: Alternating COPP/ABVD and rapid alternating COPP/ABV/IMEP in combination with extended-field radiotherapy are equally effective in intermediate-stage Hodgkin's lymphoma and produce excellent long-term treatment results.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hodgkin Disease/drug therapy , Hodgkin Disease/radiotherapy , Adolescent , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Bleomycin/administration & dosage , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Dacarbazine/administration & dosage , Disease-Free Survival , Doxorubicin/administration & dosage , Etoposide/administration & dosage , Female , Hodgkin Disease/pathology , Humans , Ifosfamide/administration & dosage , Male , Methotrexate/administration & dosage , Middle Aged , Prednisone/administration & dosage , Procarbazine/administration & dosage , Treatment Outcome , Vinblastine/administration & dosage , Vincristine/administration & dosage
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