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Fractionated cyclophosphamide added to the IVAP regimen (idarubicin-vincristine-L-asparaginase-prednisone) could lower the risk of primary refractory disease in T-lineage but not B-lineage acute lymphoblastic leukemia: first results from a phase II clinical study.
Haematologica. 1999 Dec; 84(12):1088-93.H

Abstract

BACKGROUND AND OBJECTIVE

In a prior study, primary resistant acute lymphoblastic leukemia (RES-ALL) was observed in 11 of 176 (6%) adult patients treated with a four drug regimen (IVAP), its incidence being higher in T-cell or Philadelphia (Ph) chromosome/BCR-ABL rearrangement positive ALL cases with a blast cell count >25x10(9)/L (RES-ALL rate 19%, p=0.04). Aiming to minimize this percentage of resistant disease, fractionated cyclophosphamide (f-CY) was then added to the IVAP regimen.

DESIGN AND METHODS

Study 08-96 was a prospective, collaborative phase II trial carried out at eight general hospital centers specialized in the care of hematologic malignancies. Historical IVAP-treated patients served as a retrospective control group. All consecutive, untreated patients (>15 years) with a diagnosis of ALL or advanced-stage lymphoblastic lymphoma (LBL) were eligible. RES-ALL was defined as the persistence of >5% ALL cells in the bone marrow 28-40 days after the start of the IVAP regimen (idarubicin 10 mg/m(2)/d on days 1 and 2; vincristine 2 mg on days 1, 8 and 15; L-asparaginase 6,000 U/m(2) on alternate days 3 6 from day 8; prednisone 60 mg/m(2)/d on days 1-21). In the new study, two f-CY schedules were sequentially adopted: CY 150 or 75 mg/m(2)/bd, given for 4 consecutive days before IVAP (f-CY 1200 or 600, expressing total CY dose in mg/m(2)).

RESULTS

Eighty-eight patients were evaluable (age range 15-74 years, blast count 0-240x10(9)/L, 14 T-lineage, 74 B-lineage, 13 Ph/BCR-ABL+). The first 39 patients received the f-CY 1200 schedule, 22 patients received f-CY 600, and the last 27 patients were not given any f-CY. These changes were dictated by the results of interim analyses of the f-CY groups (RES-ALL rate not reduced, myelotoxicity increased). Altogether, compared with the historical IVAP and no f-CY groups, the incidence of RES-ALL was not decreased by the addition of f-CY 1200/600 in B-lineage ALL, regardless of Ph/BCR-ABL expression and blast count. However, none of 14 T-ALL cases in the new study had RES-ALL (8 in f-CY groups, 5 of whom with >25x10(9)/L blast cells), compared to 5/39 (13%, overall) or 4/21 (19%, with >25x10(9)/L blast cells) among the control cases. Owing to small sample size, this difference was not statistically significant.

INTERPRETATION AND CONCLUSIONS

This preliminary experience suggests that T-ALL may be more sensitive than B-lineage ALL to an early therapy including f-CY. The hypothesis could be tested in a larger clinical trial.

Authors+Show Affiliations

Ematologia, Ospedali Riuniti, largo Barozzi 1, 24100 Bergamo, Italy. ematologia@cyberg.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Clinical Trial, Phase II
Journal Article
Multicenter Study

Language

eng

PubMed ID

10586210

Citation

Bassan, R, et al. "Fractionated Cyclophosphamide Added to the IVAP Regimen (idarubicin-vincristine-L-asparaginase-prednisone) Could Lower the Risk of Primary Refractory Disease in T-lineage but Not B-lineage Acute Lymphoblastic Leukemia: First Results From a Phase II Clinical Study." Haematologica, vol. 84, no. 12, 1999, pp. 1088-93.
Bassan R, Pogliani E, Lerede T, et al. Fractionated cyclophosphamide added to the IVAP regimen (idarubicin-vincristine-L-asparaginase-prednisone) could lower the risk of primary refractory disease in T-lineage but not B-lineage acute lymphoblastic leukemia: first results from a phase II clinical study. Haematologica. 1999;84(12):1088-93.
Bassan, R., Pogliani, E., Lerede, T., Fabris, P., Rossi, G., Morandi, S., Casula, P., Lambertenghi-Deliliers, G., Vespignani, M., Izzi, T., Coser, P., Corneo, G., & Barbui, T. (1999). Fractionated cyclophosphamide added to the IVAP regimen (idarubicin-vincristine-L-asparaginase-prednisone) could lower the risk of primary refractory disease in T-lineage but not B-lineage acute lymphoblastic leukemia: first results from a phase II clinical study. Haematologica, 84(12), 1088-93.
Bassan R, et al. Fractionated Cyclophosphamide Added to the IVAP Regimen (idarubicin-vincristine-L-asparaginase-prednisone) Could Lower the Risk of Primary Refractory Disease in T-lineage but Not B-lineage Acute Lymphoblastic Leukemia: First Results From a Phase II Clinical Study. Haematologica. 1999;84(12):1088-93. PubMed PMID: 10586210.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fractionated cyclophosphamide added to the IVAP regimen (idarubicin-vincristine-L-asparaginase-prednisone) could lower the risk of primary refractory disease in T-lineage but not B-lineage acute lymphoblastic leukemia: first results from a phase II clinical study. AU - Bassan,R, AU - Pogliani,E, AU - Lerede,T, AU - Fabris,P, AU - Rossi,G, AU - Morandi,S, AU - Casula,P, AU - Lambertenghi-Deliliers,G, AU - Vespignani,M, AU - Izzi,T, AU - Coser,P, AU - Corneo,G, AU - Barbui,T, PY - 1999/12/10/pubmed PY - 2000/3/4/medline PY - 1999/12/10/entrez SP - 1088 EP - 93 JF - Haematologica JO - Haematologica VL - 84 IS - 12 N2 - BACKGROUND AND OBJECTIVE: In a prior study, primary resistant acute lymphoblastic leukemia (RES-ALL) was observed in 11 of 176 (6%) adult patients treated with a four drug regimen (IVAP), its incidence being higher in T-cell or Philadelphia (Ph) chromosome/BCR-ABL rearrangement positive ALL cases with a blast cell count >25x10(9)/L (RES-ALL rate 19%, p=0.04). Aiming to minimize this percentage of resistant disease, fractionated cyclophosphamide (f-CY) was then added to the IVAP regimen. DESIGN AND METHODS: Study 08-96 was a prospective, collaborative phase II trial carried out at eight general hospital centers specialized in the care of hematologic malignancies. Historical IVAP-treated patients served as a retrospective control group. All consecutive, untreated patients (>15 years) with a diagnosis of ALL or advanced-stage lymphoblastic lymphoma (LBL) were eligible. RES-ALL was defined as the persistence of >5% ALL cells in the bone marrow 28-40 days after the start of the IVAP regimen (idarubicin 10 mg/m(2)/d on days 1 and 2; vincristine 2 mg on days 1, 8 and 15; L-asparaginase 6,000 U/m(2) on alternate days 3 6 from day 8; prednisone 60 mg/m(2)/d on days 1-21). In the new study, two f-CY schedules were sequentially adopted: CY 150 or 75 mg/m(2)/bd, given for 4 consecutive days before IVAP (f-CY 1200 or 600, expressing total CY dose in mg/m(2)). RESULTS: Eighty-eight patients were evaluable (age range 15-74 years, blast count 0-240x10(9)/L, 14 T-lineage, 74 B-lineage, 13 Ph/BCR-ABL+). The first 39 patients received the f-CY 1200 schedule, 22 patients received f-CY 600, and the last 27 patients were not given any f-CY. These changes were dictated by the results of interim analyses of the f-CY groups (RES-ALL rate not reduced, myelotoxicity increased). Altogether, compared with the historical IVAP and no f-CY groups, the incidence of RES-ALL was not decreased by the addition of f-CY 1200/600 in B-lineage ALL, regardless of Ph/BCR-ABL expression and blast count. However, none of 14 T-ALL cases in the new study had RES-ALL (8 in f-CY groups, 5 of whom with >25x10(9)/L blast cells), compared to 5/39 (13%, overall) or 4/21 (19%, with >25x10(9)/L blast cells) among the control cases. Owing to small sample size, this difference was not statistically significant. INTERPRETATION AND CONCLUSIONS: This preliminary experience suggests that T-ALL may be more sensitive than B-lineage ALL to an early therapy including f-CY. The hypothesis could be tested in a larger clinical trial. SN - 0390-6078 UR - https://www.unboundmedicine.com/medline/citation/10586210/Fractionated_cyclophosphamide_added_to_the_IVAP_regimen__idarubicin_vincristine_L_asparaginase_prednisone__could_lower_the_risk_of_primary_refractory_disease_in_T_lineage_but_not_B_lineage_acute_lymphoblastic_leukemia:_first_results_from_a_phase_II_clinical_study_ L2 - http://www.diseaseinfosearch.org/result/188 DB - PRIME DP - Unbound Medicine ER -