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THE IMPACT OF RISK STRATIFICATION BY EARLY BONE-MARROW RESPONSE IN CHILDHOOD T- ACUTE LYMPHOBLASTIC LEUKAEMIA (A SINGLE INSTITUTION EXPERIENCE IN AZIZA OTHMANA HOSPITAL, TUNIS, TUNISIA).
Author(s): ,
Ben Abdennebi Yosr
Affiliations:
Clinical Hematology, Aziza Othmana Hospital,Hospital Aziza Othmana,Tunis,Tunisia;Clinical Hematology, Aziza Othmana Hospital,Hospital Aziza Othmana,Tunis,Tunisia
,
Khayati Yasmine
Affiliations:
Clinical Hematology, Aziza Othmana Hospital,Hospital Aziza Othmana,Tunis,Tunisia
,
Jaidi Rim
Affiliations:
Clinical Hematology, Aziza Othmana Hospital,Hospital Aziza Othmana,Tunis,Tunisia
,
Charef Ons
Affiliations:
Clinical Hematology, Aziza Othmana Hospital,Hospital Aziza Othmana,Tunis,Tunisia
,
Bahri Marwa
Affiliations:
Clinical Hematology, Aziza Othmana Hospital,Hospital Aziza Othmana,Tunis,Tunisia
,
Bchir Manel
Affiliations:
Clinical Hematology, Aziza Othmana Hospital,Hospital Aziza Othmana,Tunis,Tunisia
,
Kefi Salma
Affiliations:
Clinical Hematology, Aziza Othmana Hospital,Hospital Aziza Othmana,Tunis,Tunisia
,
Achour Mariem
Affiliations:
Clinical Hematology, Aziza Othmana Hospital,Hospital Aziza Othmana,Tunis,Tunisia
,
Ben Lakhal Rayhane
Affiliations:
Clinical Hematology, Aziza Othmana Hospital,Hospital Aziza Othmana,Tunis,Tunisia
,
Meddeb Balkis
Affiliations:
Clinical Hematology, Aziza Othmana Hospital,Hospital Aziza Othmana,Tunis,Tunisia
Aissaoui Lamia
Affiliations:
Clinical Hematology, Aziza Othmana Hospital,Hospital Aziza Othmana,Tunis,Tunisia
EHA Library. Abdennebi Yosr B. 06/09/21; 324056; PB1371
Ben Abdennebi Yosr
Ben Abdennebi Yosr
Contributions
Abstract

Abstract: PB1371

Type: Publication Only

Session title: Acute lymphoblastic leukemia - Clinical

Background
T-cell acute lymphoblastic leukemia (T-ALL) represents approximately  15% of all newly diagnosed  ALL  cases in pediatric patients. Although historically, outcomes for T-ALL were inferior to those of B lymphoblastic leukemia (B-ALL), the prognosis of T-ALL has been steadily improving in recent years due to increased chemotherapy protocols in particular with the use of high doses of Methotrexate and Asparaginase.

Aims
This study aimed to assess the therapeutic  outcomes of children and adolescents with T-ALL treated according to the EORTC 58951 protocol, patients were stratified by age, WBC at diagnosis, immunophenotype, karyotype and steroids response in peripheral smears after 7 days of corticosteroid and one IT dose of MTX.  The stratification strategy was extended by additional use of early response to therapy: blast cell count in the bone marrow (BM) was examinated on D19 during remission induction, and determination of MRD measured by FCM in the BM at the end of induction (D35). All patients were assigned to a DXM based induction. Patients whose blast cells were ≥ 25% in BM (M3 marrow) at D 19, or whose MRD was positive at the end of induction, had their treatment one step upgraded.

Methods
Between January 2006 and  December 2017, 377 children and adolescents with previously untreated ALL were treated according to the EORTC 58951 protocol, 93 (24.6%) have T-ALL.  Median age was 13 years (18months to 25 years), the ratio of male to female was 4.1: 1 , 7.5% and 2.7% have initial system nervous system and testicular involvement, Median WBC was 61.5 G/l ( 1.5 – 960 G/l) and  40.9% with a WBC ≥ 100 Giga/l.

Results
All patients received phase IA RM2- VHR according to the EORTC58951 protocol, with a 4-drug induction containing dexamethasone and an early introduction of Methotrexate high dose on day 8 and Cyclophosphamide on day 9.  42.4% were steroid poor responders at  day 8 in in the peripheral blood (pB) . On day 19, 18.4% had M3 marrow. The CR was 88,2%, induction failure and induction death rates were 6.5% and 5.3% respectively. MRD results detected by a simplified flow cytometric assay, sensitivity of 0,01%, between 0,01% and 0,1% , between 0,1% and  >1%  was achieved respectively in 40.3%, 34.7%, 20.8% and 4.2%.

 


41.4%  were assigned to the average 2 risk (AR2) group , 37.9% to the very high risk (VHR) group and 20.7% had received sibling stem cell transplantation in 1st CR.


 The 5-year OS, EFS and RFS were 72.9%, 66.4%  and 77.7% respectively. In Univariate analyses, WBC< 100 G/l, no M3 bone marrow on day 19 and complete remission at the end of induction have a significantly better OS. The prognostic value of morphological assessment of bone marrow blasts on day 19 during remission induction and the achieving of complete remission at the end of induction were the most prognostic factors for EFS and RFS.The 5-year OS was 90% for patients assigned to AR2 group, 66.4% for VHR and 76.9% for sibling stem cell transplant in CR1 (p : 0.04).

Conclusion
 Early treatment response as assessed by morphological examination has important prognostic significance, and can be performed in a resource poor patient population.

Keyword(s):

Abstract: PB1371

Type: Publication Only

Session title: Acute lymphoblastic leukemia - Clinical

Background
T-cell acute lymphoblastic leukemia (T-ALL) represents approximately  15% of all newly diagnosed  ALL  cases in pediatric patients. Although historically, outcomes for T-ALL were inferior to those of B lymphoblastic leukemia (B-ALL), the prognosis of T-ALL has been steadily improving in recent years due to increased chemotherapy protocols in particular with the use of high doses of Methotrexate and Asparaginase.

Aims
This study aimed to assess the therapeutic  outcomes of children and adolescents with T-ALL treated according to the EORTC 58951 protocol, patients were stratified by age, WBC at diagnosis, immunophenotype, karyotype and steroids response in peripheral smears after 7 days of corticosteroid and one IT dose of MTX.  The stratification strategy was extended by additional use of early response to therapy: blast cell count in the bone marrow (BM) was examinated on D19 during remission induction, and determination of MRD measured by FCM in the BM at the end of induction (D35). All patients were assigned to a DXM based induction. Patients whose blast cells were ≥ 25% in BM (M3 marrow) at D 19, or whose MRD was positive at the end of induction, had their treatment one step upgraded.

Methods
Between January 2006 and  December 2017, 377 children and adolescents with previously untreated ALL were treated according to the EORTC 58951 protocol, 93 (24.6%) have T-ALL.  Median age was 13 years (18months to 25 years), the ratio of male to female was 4.1: 1 , 7.5% and 2.7% have initial system nervous system and testicular involvement, Median WBC was 61.5 G/l ( 1.5 – 960 G/l) and  40.9% with a WBC ≥ 100 Giga/l.

Results
All patients received phase IA RM2- VHR according to the EORTC58951 protocol, with a 4-drug induction containing dexamethasone and an early introduction of Methotrexate high dose on day 8 and Cyclophosphamide on day 9.  42.4% were steroid poor responders at  day 8 in in the peripheral blood (pB) . On day 19, 18.4% had M3 marrow. The CR was 88,2%, induction failure and induction death rates were 6.5% and 5.3% respectively. MRD results detected by a simplified flow cytometric assay, sensitivity of 0,01%, between 0,01% and 0,1% , between 0,1% and  >1%  was achieved respectively in 40.3%, 34.7%, 20.8% and 4.2%.

 


41.4%  were assigned to the average 2 risk (AR2) group , 37.9% to the very high risk (VHR) group and 20.7% had received sibling stem cell transplantation in 1st CR.


 The 5-year OS, EFS and RFS were 72.9%, 66.4%  and 77.7% respectively. In Univariate analyses, WBC< 100 G/l, no M3 bone marrow on day 19 and complete remission at the end of induction have a significantly better OS. The prognostic value of morphological assessment of bone marrow blasts on day 19 during remission induction and the achieving of complete remission at the end of induction were the most prognostic factors for EFS and RFS.The 5-year OS was 90% for patients assigned to AR2 group, 66.4% for VHR and 76.9% for sibling stem cell transplant in CR1 (p : 0.04).

Conclusion
 Early treatment response as assessed by morphological examination has important prognostic significance, and can be performed in a resource poor patient population.

Keyword(s):

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