Factors Affecting Post-Transplant Relapse of Acute Lymphoblastic Leukemia (ALL) in Children According on the Intensity of Conditioning

Factors Affecting Post-Transplant Relapse of Acute Lymphoblastic Leukemia (ALL) in Children According on the Intensity of Conditioning

Background: Relapse of ALL remains the major cause of transplant failure. Relapse incidence after allo-HSCT is described in 30-40% of patients. Patients with ALL receive allo-HSCT with MAC more often because after RIC more relapses are expected. The aim: To compare the frequency of relapse after all...

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Veröffentlicht in:Blood 2020-11, Vol.136 (Supplement 1), p.26-27
Hauptverfasser: Semenova, Elena Vladimirovna, Kozhokar, Polina Valerievna, Paina, Olesia V, Rakhmanova, Zhemal Zarifovna, Frolova, Anastasia S, Tsvetkova, Luibov, Ekushov, Kirill Alexandrovich, Bykova, Tatiana A, Osipova, Anna A., Markova, Inna, Bondarenko, Sergey N., Smirnov, Boris I, Barkhatov, Ildar M, Gindina, Tatyana L., Moiseev, Ivan S., Zander, Axel R., Zubarovskaya, Ludmila S
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container_issue Supplement 1
container_start_page 26
container_title Blood
container_volume 136
creator Semenova, Elena Vladimirovna
Kozhokar, Polina Valerievna
Paina, Olesia V
Rakhmanova, Zhemal Zarifovna
Frolova, Anastasia S
Tsvetkova, Luibov
Ekushov, Kirill Alexandrovich
Bykova, Tatiana A
Osipova, Anna A.
Markova, Inna
Bondarenko, Sergey N.
Smirnov, Boris I
Barkhatov, Ildar M
Gindina, Tatyana L.
Moiseev, Ivan S.
Zander, Axel R.
Zubarovskaya, Ludmila S
description Background: Relapse of ALL remains the major cause of transplant failure. Relapse incidence after allo-HSCT is described in 30-40% of patients. Patients with ALL receive allo-HSCT with MAC more often because after RIC more relapses are expected. The aim: To compare the frequency of relapse after allo-HSCT with RIC vs with MAC and to analyze the factors influencing the risk of relapse depending on the intensity of conditioning regimens. Patients and methods: Between 12/2000 and 09/2019 at RM Gorbacheva Research Institute a total of 235 children with ALL (median age of 10 years (0,5-18), underwent allo-HSCT. MAC (busulfan- or treosulfan-based) were used in 163 pts: 1st CR - 30 pts (MRD+ n=13), 2nd CR - 58 pts, 3rd or 4 CR - 27 pts, relapse - 48 pts. Allo-HSCT with RIC were performed in 72 pts: 1st CR - 12 pts (MRD+ n=9), 2nd CR - 29 pts, 3rd or 4 CR - 14 pts, relapse -17 pts. RIC consisted of fludarabine (30 mg/m2/d x 5 days) + melphalan (70 mg/m2/d x 2 days) or fludarabine (30 mg/m2/d x 5 days) + busulfan (4 mg/kg/d x 2 days). Matched related allo-HSCT was performed in 37 pts (16%), matched unrelated - in 128 pts (54%), haploidentical-in 70 pts (30%). Cumulative incidence functions were used to estimate relapse incidence and NRM in a competing risk setting. Univariate analyses were performed using Grey test for cumulative incidences. Multivariate analyses were performed using the Cox proportional-hazard model. Results: Median follow-up was 5,4 and 4,5 years for МАС and RIC, respectively. Relapses were diagnosed in 105 pts (44%) during 1-39 months after allo-HSCT (median 7.5 months) (90% relapses were during first 18 mo), 74 pts after MAC; 31 pts after RIC (p=0,549). Relapses occurred significantly less frequent (p=0,007) in patients who had CR at the moment of allo-HSCT - 61 pts (35%) (RIC -32%; MAC -37%) compared patients who had a relapse or primary resistance 44 pts (68%) (RIC-74%; MAC - 65%). The risk of relapse after MAC is influenced by the presence of acute GVHD (p=0,007), the source of HSCs (PBSC vs BM, p=0,032), and the status of the disease (CR vs relapse) at the moment of allo-HSCT (p=0,001). The risk of relapse after RIC is influenced by the presence of acute GVHD (p=0,042), age at the moment of allo-HSCT 1-10 years (p=0,032), and the status of the disease (CR vs relapse) at the moment of allo-HSCT (p=0,001). Multivariable analysis confirmed a significant impact of disease status at the moment of allo-HSCT whit MAC (p=0,001) and with RIC (p=0,00
doi_str_mv 10.1182/blood-2020-139466
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Relapse incidence after allo-HSCT is described in 30-40% of patients. Patients with ALL receive allo-HSCT with MAC more often because after RIC more relapses are expected. The aim: To compare the frequency of relapse after allo-HSCT with RIC vs with MAC and to analyze the factors influencing the risk of relapse depending on the intensity of conditioning regimens. Patients and methods: Between 12/2000 and 09/2019 at RM Gorbacheva Research Institute a total of 235 children with ALL (median age of 10 years (0,5-18), underwent allo-HSCT. MAC (busulfan- or treosulfan-based) were used in 163 pts: 1st CR - 30 pts (MRD+ n=13), 2nd CR - 58 pts, 3rd or 4 CR - 27 pts, relapse - 48 pts. Allo-HSCT with RIC were performed in 72 pts: 1st CR - 12 pts (MRD+ n=9), 2nd CR - 29 pts, 3rd or 4 CR - 14 pts, relapse -17 pts. RIC consisted of fludarabine (30 mg/m2/d x 5 days) + melphalan (70 mg/m2/d x 2 days) or fludarabine (30 mg/m2/d x 5 days) + busulfan (4 mg/kg/d x 2 days). Matched related allo-HSCT was performed in 37 pts (16%), matched unrelated - in 128 pts (54%), haploidentical-in 70 pts (30%). Cumulative incidence functions were used to estimate relapse incidence and NRM in a competing risk setting. Univariate analyses were performed using Grey test for cumulative incidences. Multivariate analyses were performed using the Cox proportional-hazard model. Results: Median follow-up was 5,4 and 4,5 years for МАС and RIC, respectively. Relapses were diagnosed in 105 pts (44%) during 1-39 months after allo-HSCT (median 7.5 months) (90% relapses were during first 18 mo), 74 pts after MAC; 31 pts after RIC (p=0,549). Relapses occurred significantly less frequent (p=0,007) in patients who had CR at the moment of allo-HSCT - 61 pts (35%) (RIC -32%; MAC -37%) compared patients who had a relapse or primary resistance 44 pts (68%) (RIC-74%; MAC - 65%). The risk of relapse after MAC is influenced by the presence of acute GVHD (p=0,007), the source of HSCs (PBSC vs BM, p=0,032), and the status of the disease (CR vs relapse) at the moment of allo-HSCT (p=0,001). The risk of relapse after RIC is influenced by the presence of acute GVHD (p=0,042), age at the moment of allo-HSCT 1-10 years (p=0,032), and the status of the disease (CR vs relapse) at the moment of allo-HSCT (p=0,001). Multivariable analysis confirmed a significant impact of disease status at the moment of allo-HSCT whit MAC (p=0,001) and with RIC (p=0,002). Presence of aGVHD was additional factor associated with lower relapse risk in multivariate analysis in pts after MAC (p=0,005). Patients with active disease at the moment of HSCT had higher relapse-free survival after RIC (RIC-23% vs MAC- 12%, p=0,012). Salvage patients in whom the relapse was documented after HSCT had 28% and 38% probability of long-term OS after RIC and MAC, respectively (p=0,572). Conclusion: Relapse incidence after allo-HSCT with MAC and with RIC is comparable. The most significant factor affecting the risk of relapse is the status of the disease at the moment of allo-HSCT. No relevant conflicts of interest to declare.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2020-139466</identifier><language>eng</language><publisher>Elsevier Inc</publisher><ispartof>Blood, 2020-11, Vol.136 (Supplement 1), p.26-27</ispartof><rights>2020 American Society of Hematology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,782,786,27931,27932</link.rule.ids></links><search><creatorcontrib>Semenova, Elena Vladimirovna</creatorcontrib><creatorcontrib>Kozhokar, Polina Valerievna</creatorcontrib><creatorcontrib>Paina, Olesia V</creatorcontrib><creatorcontrib>Rakhmanova, Zhemal Zarifovna</creatorcontrib><creatorcontrib>Frolova, Anastasia S</creatorcontrib><creatorcontrib>Tsvetkova, Luibov</creatorcontrib><creatorcontrib>Ekushov, Kirill Alexandrovich</creatorcontrib><creatorcontrib>Bykova, Tatiana A</creatorcontrib><creatorcontrib>Osipova, Anna A.</creatorcontrib><creatorcontrib>Markova, Inna</creatorcontrib><creatorcontrib>Bondarenko, Sergey N.</creatorcontrib><creatorcontrib>Smirnov, Boris I</creatorcontrib><creatorcontrib>Barkhatov, Ildar M</creatorcontrib><creatorcontrib>Gindina, Tatyana L.</creatorcontrib><creatorcontrib>Moiseev, Ivan S.</creatorcontrib><creatorcontrib>Zander, Axel R.</creatorcontrib><creatorcontrib>Zubarovskaya, Ludmila S</creatorcontrib><title>Factors Affecting Post-Transplant Relapse of Acute Lymphoblastic Leukemia (ALL) in Children According on the Intensity of Conditioning</title><title>Blood</title><description>Background: Relapse of ALL remains the major cause of transplant failure. Relapse incidence after allo-HSCT is described in 30-40% of patients. Patients with ALL receive allo-HSCT with MAC more often because after RIC more relapses are expected. The aim: To compare the frequency of relapse after allo-HSCT with RIC vs with MAC and to analyze the factors influencing the risk of relapse depending on the intensity of conditioning regimens. Patients and methods: Between 12/2000 and 09/2019 at RM Gorbacheva Research Institute a total of 235 children with ALL (median age of 10 years (0,5-18), underwent allo-HSCT. MAC (busulfan- or treosulfan-based) were used in 163 pts: 1st CR - 30 pts (MRD+ n=13), 2nd CR - 58 pts, 3rd or 4 CR - 27 pts, relapse - 48 pts. Allo-HSCT with RIC were performed in 72 pts: 1st CR - 12 pts (MRD+ n=9), 2nd CR - 29 pts, 3rd or 4 CR - 14 pts, relapse -17 pts. RIC consisted of fludarabine (30 mg/m2/d x 5 days) + melphalan (70 mg/m2/d x 2 days) or fludarabine (30 mg/m2/d x 5 days) + busulfan (4 mg/kg/d x 2 days). Matched related allo-HSCT was performed in 37 pts (16%), matched unrelated - in 128 pts (54%), haploidentical-in 70 pts (30%). Cumulative incidence functions were used to estimate relapse incidence and NRM in a competing risk setting. Univariate analyses were performed using Grey test for cumulative incidences. Multivariate analyses were performed using the Cox proportional-hazard model. Results: Median follow-up was 5,4 and 4,5 years for МАС and RIC, respectively. Relapses were diagnosed in 105 pts (44%) during 1-39 months after allo-HSCT (median 7.5 months) (90% relapses were during first 18 mo), 74 pts after MAC; 31 pts after RIC (p=0,549). Relapses occurred significantly less frequent (p=0,007) in patients who had CR at the moment of allo-HSCT - 61 pts (35%) (RIC -32%; MAC -37%) compared patients who had a relapse or primary resistance 44 pts (68%) (RIC-74%; MAC - 65%). The risk of relapse after MAC is influenced by the presence of acute GVHD (p=0,007), the source of HSCs (PBSC vs BM, p=0,032), and the status of the disease (CR vs relapse) at the moment of allo-HSCT (p=0,001). The risk of relapse after RIC is influenced by the presence of acute GVHD (p=0,042), age at the moment of allo-HSCT 1-10 years (p=0,032), and the status of the disease (CR vs relapse) at the moment of allo-HSCT (p=0,001). Multivariable analysis confirmed a significant impact of disease status at the moment of allo-HSCT whit MAC (p=0,001) and with RIC (p=0,002). Presence of aGVHD was additional factor associated with lower relapse risk in multivariate analysis in pts after MAC (p=0,005). Patients with active disease at the moment of HSCT had higher relapse-free survival after RIC (RIC-23% vs MAC- 12%, p=0,012). Salvage patients in whom the relapse was documented after HSCT had 28% and 38% probability of long-term OS after RIC and MAC, respectively (p=0,572). Conclusion: Relapse incidence after allo-HSCT with MAC and with RIC is comparable. The most significant factor affecting the risk of relapse is the status of the disease at the moment of allo-HSCT. No relevant conflicts of interest to declare.</description><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9kMFKxDAURYMoOI5-gLssdRFN2rST4qoURwcKiozrkCavTrSTDEkU5gf8blvHtasHl3suj4PQJaM3jInsthu8NySjGSUsr3hZHqEZKzJB6BgdoxmltCS8WrBTdBbjO6WM51kxQ99LpZMPEdd9DzpZ94affUxkHZSLu0G5hF9gULsI2Pe41p8JcLvf7ja-G1RMVuMWPj9gaxW-qtv2GluHm40dTAA31rUPZtr0DqcN4JVL4KJN-2ms8c7YZL0bC-fopFdDhIu_O0evy_t180jap4dVU7dEs3xREpErgKpjmcm50pUwTJRK9N2i6KDg3HSFqaBQZow0M0UumAbgVdf3pSg6wfM5YoddHXyMAXq5C3arwl4yKieR8leknETKg8iRuTswMD72ZSHIqC04DcaGUZk03v5D_wCF134s</recordid><startdate>20201105</startdate><enddate>20201105</enddate><creator>Semenova, Elena Vladimirovna</creator><creator>Kozhokar, Polina Valerievna</creator><creator>Paina, Olesia V</creator><creator>Rakhmanova, Zhemal Zarifovna</creator><creator>Frolova, Anastasia S</creator><creator>Tsvetkova, Luibov</creator><creator>Ekushov, Kirill Alexandrovich</creator><creator>Bykova, Tatiana A</creator><creator>Osipova, Anna A.</creator><creator>Markova, Inna</creator><creator>Bondarenko, Sergey N.</creator><creator>Smirnov, Boris I</creator><creator>Barkhatov, Ildar M</creator><creator>Gindina, Tatyana L.</creator><creator>Moiseev, Ivan S.</creator><creator>Zander, Axel R.</creator><creator>Zubarovskaya, Ludmila S</creator><general>Elsevier Inc</general><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20201105</creationdate><title>Factors Affecting Post-Transplant Relapse of Acute Lymphoblastic Leukemia (ALL) in Children According on the Intensity of Conditioning</title><author>Semenova, Elena Vladimirovna ; Kozhokar, Polina Valerievna ; Paina, Olesia V ; Rakhmanova, Zhemal Zarifovna ; Frolova, Anastasia S ; Tsvetkova, Luibov ; Ekushov, Kirill Alexandrovich ; Bykova, Tatiana A ; Osipova, Anna A. ; Markova, Inna ; Bondarenko, Sergey N. ; Smirnov, Boris I ; Barkhatov, Ildar M ; Gindina, Tatyana L. ; Moiseev, Ivan S. ; Zander, Axel R. ; Zubarovskaya, Ludmila S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1376-83aee9b12d34ac98d186a8fb75be544db5d9e5ad8fbc1d5381cee49bff685b843</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Semenova, Elena Vladimirovna</creatorcontrib><creatorcontrib>Kozhokar, Polina Valerievna</creatorcontrib><creatorcontrib>Paina, Olesia V</creatorcontrib><creatorcontrib>Rakhmanova, Zhemal Zarifovna</creatorcontrib><creatorcontrib>Frolova, Anastasia S</creatorcontrib><creatorcontrib>Tsvetkova, Luibov</creatorcontrib><creatorcontrib>Ekushov, Kirill Alexandrovich</creatorcontrib><creatorcontrib>Bykova, Tatiana A</creatorcontrib><creatorcontrib>Osipova, Anna A.</creatorcontrib><creatorcontrib>Markova, Inna</creatorcontrib><creatorcontrib>Bondarenko, Sergey N.</creatorcontrib><creatorcontrib>Smirnov, Boris I</creatorcontrib><creatorcontrib>Barkhatov, Ildar M</creatorcontrib><creatorcontrib>Gindina, Tatyana L.</creatorcontrib><creatorcontrib>Moiseev, Ivan S.</creatorcontrib><creatorcontrib>Zander, Axel R.</creatorcontrib><creatorcontrib>Zubarovskaya, Ludmila S</creatorcontrib><collection>CrossRef</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Semenova, Elena Vladimirovna</au><au>Kozhokar, Polina Valerievna</au><au>Paina, Olesia V</au><au>Rakhmanova, Zhemal Zarifovna</au><au>Frolova, Anastasia S</au><au>Tsvetkova, Luibov</au><au>Ekushov, Kirill Alexandrovich</au><au>Bykova, Tatiana A</au><au>Osipova, Anna A.</au><au>Markova, Inna</au><au>Bondarenko, Sergey N.</au><au>Smirnov, Boris I</au><au>Barkhatov, Ildar M</au><au>Gindina, Tatyana L.</au><au>Moiseev, Ivan S.</au><au>Zander, Axel R.</au><au>Zubarovskaya, Ludmila S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Factors Affecting Post-Transplant Relapse of Acute Lymphoblastic Leukemia (ALL) in Children According on the Intensity of Conditioning</atitle><jtitle>Blood</jtitle><date>2020-11-05</date><risdate>2020</risdate><volume>136</volume><issue>Supplement 1</issue><spage>26</spage><epage>27</epage><pages>26-27</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>Background: Relapse of ALL remains the major cause of transplant failure. Relapse incidence after allo-HSCT is described in 30-40% of patients. Patients with ALL receive allo-HSCT with MAC more often because after RIC more relapses are expected. The aim: To compare the frequency of relapse after allo-HSCT with RIC vs with MAC and to analyze the factors influencing the risk of relapse depending on the intensity of conditioning regimens. Patients and methods: Between 12/2000 and 09/2019 at RM Gorbacheva Research Institute a total of 235 children with ALL (median age of 10 years (0,5-18), underwent allo-HSCT. MAC (busulfan- or treosulfan-based) were used in 163 pts: 1st CR - 30 pts (MRD+ n=13), 2nd CR - 58 pts, 3rd or 4 CR - 27 pts, relapse - 48 pts. Allo-HSCT with RIC were performed in 72 pts: 1st CR - 12 pts (MRD+ n=9), 2nd CR - 29 pts, 3rd or 4 CR - 14 pts, relapse -17 pts. RIC consisted of fludarabine (30 mg/m2/d x 5 days) + melphalan (70 mg/m2/d x 2 days) or fludarabine (30 mg/m2/d x 5 days) + busulfan (4 mg/kg/d x 2 days). Matched related allo-HSCT was performed in 37 pts (16%), matched unrelated - in 128 pts (54%), haploidentical-in 70 pts (30%). Cumulative incidence functions were used to estimate relapse incidence and NRM in a competing risk setting. Univariate analyses were performed using Grey test for cumulative incidences. Multivariate analyses were performed using the Cox proportional-hazard model. Results: Median follow-up was 5,4 and 4,5 years for МАС and RIC, respectively. Relapses were diagnosed in 105 pts (44%) during 1-39 months after allo-HSCT (median 7.5 months) (90% relapses were during first 18 mo), 74 pts after MAC; 31 pts after RIC (p=0,549). Relapses occurred significantly less frequent (p=0,007) in patients who had CR at the moment of allo-HSCT - 61 pts (35%) (RIC -32%; MAC -37%) compared patients who had a relapse or primary resistance 44 pts (68%) (RIC-74%; MAC - 65%). The risk of relapse after MAC is influenced by the presence of acute GVHD (p=0,007), the source of HSCs (PBSC vs BM, p=0,032), and the status of the disease (CR vs relapse) at the moment of allo-HSCT (p=0,001). The risk of relapse after RIC is influenced by the presence of acute GVHD (p=0,042), age at the moment of allo-HSCT 1-10 years (p=0,032), and the status of the disease (CR vs relapse) at the moment of allo-HSCT (p=0,001). Multivariable analysis confirmed a significant impact of disease status at the moment of allo-HSCT whit MAC (p=0,001) and with RIC (p=0,002). Presence of aGVHD was additional factor associated with lower relapse risk in multivariate analysis in pts after MAC (p=0,005). Patients with active disease at the moment of HSCT had higher relapse-free survival after RIC (RIC-23% vs MAC- 12%, p=0,012). Salvage patients in whom the relapse was documented after HSCT had 28% and 38% probability of long-term OS after RIC and MAC, respectively (p=0,572). Conclusion: Relapse incidence after allo-HSCT with MAC and with RIC is comparable. The most significant factor affecting the risk of relapse is the status of the disease at the moment of allo-HSCT. No relevant conflicts of interest to declare.</abstract><pub>Elsevier Inc</pub><doi>10.1182/blood-2020-139466</doi><tpages>2</tpages><oa>free_for_read</oa></addata></record>
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title Factors Affecting Post-Transplant Relapse of Acute Lymphoblastic Leukemia (ALL) in Children According on the Intensity of Conditioning
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