Management of acute promyelocytic leukemia relapse in the ATRA era

Divisione di Ematologia, IRCCS Policlinico S.Matteo di Pavia, Italy. castagnola@smatteo.pv.it BACKGROUND AND OBJECTIVE: The use of all-trans retinoic acid (ATRA) has changed the natural course of acute promyelocytic leukemia (APL), increasing the percentage of lasting complete remissions. However, m...

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Veröffentlicht in:Haematologica (Roma) 1998-08, Vol.83 (8), p.714
Hauptverfasser: Castagnola, C, Lunghi, M, Corso, A, Tajana, M, Zappasodi, P, Dabusti, M, Lazzarino, M, Bernasconi, C
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container_issue 8
container_start_page 714
container_title Haematologica (Roma)
container_volume 83
creator Castagnola, C
Lunghi, M
Corso, A
Tajana, M
Zappasodi, P
Dabusti, M
Lazzarino, M
Bernasconi, C
description Divisione di Ematologia, IRCCS Policlinico S.Matteo di Pavia, Italy. castagnola@smatteo.pv.it BACKGROUND AND OBJECTIVE: The use of all-trans retinoic acid (ATRA) has changed the natural course of acute promyelocytic leukemia (APL), increasing the percentage of lasting complete remissions. However, management of the few relapses remains undefined. The purpose of the present study was to evaluate the different behavior of APL patients relapsed after induction chemotherapy which had or had not included ATRA. DESIGN AND METHODS: We retrospectively studied 8 patients (3 male and 5 female) who had relapsed after a clinical and molecular complete remission (CR). Five patients relapsed after conventional chemotherapy including anthracyclines, without ATRA which was not available at the onset (group A), 3 relapsed after induction treatment according to AIDA protocol (Idarubicin + ATRA) (group B). Seven patients had both molecular and clinical relapses, 1 (group B) had only a molecular relapse. The median first CR duration was 33 months (range 8-63). To induce a second CR all patients were treated with ATRA 45 mg/m2/day given orally until CR, combined with mitoxantrone 6 mg/m2/day for 6 days and cytarabine 1 g/m2/day for 6 days. RESULTS: Seven out of 8 patients (87.5%) achieved second CR, 1 (group A) did not respond and died within two months. Second CR duration was 21, 43+, 56+, 62+ months in group A and 5, 10, 12+ (with molecular relapse) months in group B. Therefore, only one patient relapsed in group A, while all the group B patients relapsed. INTERPRETATION AND CONCLUSIONS: ATRA combined with chemotherapy is an effective approach to treating APL relapse. It produces a high incidence of second CR with an acceptable toxicity. The duration of the second CR seems, however, to be longer in patients never treated with ATRA before than in patients who relapsed after the AIDA protocol. Therefore, it might be appropriate to adopt more aggressive protocols in this latter subset of patients.
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However, management of the few relapses remains undefined. The purpose of the present study was to evaluate the different behavior of APL patients relapsed after induction chemotherapy which had or had not included ATRA. DESIGN AND METHODS: We retrospectively studied 8 patients (3 male and 5 female) who had relapsed after a clinical and molecular complete remission (CR). Five patients relapsed after conventional chemotherapy including anthracyclines, without ATRA which was not available at the onset (group A), 3 relapsed after induction treatment according to AIDA protocol (Idarubicin + ATRA) (group B). Seven patients had both molecular and clinical relapses, 1 (group B) had only a molecular relapse. The median first CR duration was 33 months (range 8-63). To induce a second CR all patients were treated with ATRA 45 mg/m2/day given orally until CR, combined with mitoxantrone 6 mg/m2/day for 6 days and cytarabine 1 g/m2/day for 6 days. RESULTS: Seven out of 8 patients (87.5%) achieved second CR, 1 (group A) did not respond and died within two months. Second CR duration was 21, 43+, 56+, 62+ months in group A and 5, 10, 12+ (with molecular relapse) months in group B. Therefore, only one patient relapsed in group A, while all the group B patients relapsed. INTERPRETATION AND CONCLUSIONS: ATRA combined with chemotherapy is an effective approach to treating APL relapse. It produces a high incidence of second CR with an acceptable toxicity. The duration of the second CR seems, however, to be longer in patients never treated with ATRA before than in patients who relapsed after the AIDA protocol. 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However, management of the few relapses remains undefined. The purpose of the present study was to evaluate the different behavior of APL patients relapsed after induction chemotherapy which had or had not included ATRA. DESIGN AND METHODS: We retrospectively studied 8 patients (3 male and 5 female) who had relapsed after a clinical and molecular complete remission (CR). Five patients relapsed after conventional chemotherapy including anthracyclines, without ATRA which was not available at the onset (group A), 3 relapsed after induction treatment according to AIDA protocol (Idarubicin + ATRA) (group B). Seven patients had both molecular and clinical relapses, 1 (group B) had only a molecular relapse. The median first CR duration was 33 months (range 8-63). To induce a second CR all patients were treated with ATRA 45 mg/m2/day given orally until CR, combined with mitoxantrone 6 mg/m2/day for 6 days and cytarabine 1 g/m2/day for 6 days. RESULTS: Seven out of 8 patients (87.5%) achieved second CR, 1 (group A) did not respond and died within two months. Second CR duration was 21, 43+, 56+, 62+ months in group A and 5, 10, 12+ (with molecular relapse) months in group B. Therefore, only one patient relapsed in group A, while all the group B patients relapsed. INTERPRETATION AND CONCLUSIONS: ATRA combined with chemotherapy is an effective approach to treating APL relapse. It produces a high incidence of second CR with an acceptable toxicity. The duration of the second CR seems, however, to be longer in patients never treated with ATRA before than in patients who relapsed after the AIDA protocol. Therefore, it might be appropriate to adopt more aggressive protocols in this latter subset of patients.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Bone Marrow Transplantation</subject><subject>Combined Modality Therapy</subject><subject>Cytarabine - administration &amp; dosage</subject><subject>Daunorubicin - administration &amp; dosage</subject><subject>Etoposide - administration &amp; dosage</subject><subject>Female</subject><subject>Humans</subject><subject>Idarubicin - administration &amp; dosage</subject><subject>Leukemia, Promyelocytic, Acute - drug therapy</subject><subject>Leukemia, Promyelocytic, Acute - mortality</subject><subject>Leukemia, Promyelocytic, Acute - therapy</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mitoxantrone - administration &amp; dosage</subject><subject>Recurrence</subject><subject>Remission Induction</subject><subject>Salvage Therapy</subject><subject>Thioguanine - administration &amp; 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dosage</topic><topic>Recurrence</topic><topic>Remission Induction</topic><topic>Salvage Therapy</topic><topic>Thioguanine - administration &amp; dosage</topic><topic>Treatment Outcome</topic><topic>Tretinoin - administration &amp; dosage</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Castagnola, C</creatorcontrib><creatorcontrib>Lunghi, M</creatorcontrib><creatorcontrib>Corso, A</creatorcontrib><creatorcontrib>Tajana, M</creatorcontrib><creatorcontrib>Zappasodi, P</creatorcontrib><creatorcontrib>Dabusti, M</creatorcontrib><creatorcontrib>Lazzarino, M</creatorcontrib><creatorcontrib>Bernasconi, C</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Haematologica (Roma)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Castagnola, C</au><au>Lunghi, M</au><au>Corso, A</au><au>Tajana, M</au><au>Zappasodi, P</au><au>Dabusti, M</au><au>Lazzarino, M</au><au>Bernasconi, C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Management of acute promyelocytic leukemia relapse in the ATRA era</atitle><jtitle>Haematologica (Roma)</jtitle><addtitle>Haematologica</addtitle><date>1998-08-01</date><risdate>1998</risdate><volume>83</volume><issue>8</issue><spage>714</spage><pages>714-</pages><issn>0390-6078</issn><eissn>1592-8721</eissn><abstract>Divisione di Ematologia, IRCCS Policlinico S.Matteo di Pavia, Italy. castagnola@smatteo.pv.it BACKGROUND AND OBJECTIVE: The use of all-trans retinoic acid (ATRA) has changed the natural course of acute promyelocytic leukemia (APL), increasing the percentage of lasting complete remissions. However, management of the few relapses remains undefined. The purpose of the present study was to evaluate the different behavior of APL patients relapsed after induction chemotherapy which had or had not included ATRA. DESIGN AND METHODS: We retrospectively studied 8 patients (3 male and 5 female) who had relapsed after a clinical and molecular complete remission (CR). Five patients relapsed after conventional chemotherapy including anthracyclines, without ATRA which was not available at the onset (group A), 3 relapsed after induction treatment according to AIDA protocol (Idarubicin + ATRA) (group B). Seven patients had both molecular and clinical relapses, 1 (group B) had only a molecular relapse. The median first CR duration was 33 months (range 8-63). To induce a second CR all patients were treated with ATRA 45 mg/m2/day given orally until CR, combined with mitoxantrone 6 mg/m2/day for 6 days and cytarabine 1 g/m2/day for 6 days. RESULTS: Seven out of 8 patients (87.5%) achieved second CR, 1 (group A) did not respond and died within two months. Second CR duration was 21, 43+, 56+, 62+ months in group A and 5, 10, 12+ (with molecular relapse) months in group B. Therefore, only one patient relapsed in group A, while all the group B patients relapsed. INTERPRETATION AND CONCLUSIONS: ATRA combined with chemotherapy is an effective approach to treating APL relapse. It produces a high incidence of second CR with an acceptable toxicity. The duration of the second CR seems, however, to be longer in patients never treated with ATRA before than in patients who relapsed after the AIDA protocol. Therefore, it might be appropriate to adopt more aggressive protocols in this latter subset of patients.</abstract><cop>Italy</cop><pmid>9793255</pmid></addata></record>
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subjects Adolescent
Adult
Antineoplastic Agents - therapeutic use
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Bone Marrow Transplantation
Combined Modality Therapy
Cytarabine - administration & dosage
Daunorubicin - administration & dosage
Etoposide - administration & dosage
Female
Humans
Idarubicin - administration & dosage
Leukemia, Promyelocytic, Acute - drug therapy
Leukemia, Promyelocytic, Acute - mortality
Leukemia, Promyelocytic, Acute - therapy
Male
Middle Aged
Mitoxantrone - administration & dosage
Recurrence
Remission Induction
Salvage Therapy
Thioguanine - administration & dosage
Treatment Outcome
Tretinoin - administration & dosage
title Management of acute promyelocytic leukemia relapse in the ATRA era
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