Abstract Trisomy 12 (tri12) is the second most frequent chromosomal aberration (15%‐20%) in chronic lymphocytic leukemia (CLL). Tri12 confers an intermediate prognosis but is a heterogeneous entity. We examined whether additional mutational or chromosomal alterations might impact tri12 patient outcomes. This retrospective study, carried out by the French Innovative Leukemia Organization, included 188 tri12 patients with comprehensive information on immunoglobulin heavy chain ( IGHV ) gene status, karyotypic/FISH abnormalities, and NOTCH1 , TP53 , SF3B1 , and MYD88 mutations. The main cytogenetic abnormalities associated with tri12 were del(13q) (25%), additional trisomies (14%) (including tri19 (10%) and tri18 (4%)), 14q32 translocations (10%), del(17p) (6.5%), del(14q) (4%), and del(11q) (4%). Unmutated (UM) IGHV , NOTCH1 , and TP53 , mutations were identified in respectively 66%, 25%, and 8.5% of cases. Multivariate analyses showed that additional trisomies (HR = 0.43, 95% CI = 0.23‐0.78, P = .01) were associated with a significantly longer time to first treatment in Binet stage A patients and with a lower risk of relapse (HR = 0.37, 95% CI = 0.15‐0.9, P = .03) in the overall tri12 population. Binet stage B/C, TP53 disruption, and UM IGHV status were associated with a shorter time to next treatment, while Binet stage B/C (HR = 4, 95% CI = 1.6‐4.9, P = .002) and TP53 disruption (HR = 5, 95% CI = 1.94‐12.66, P = .001) conferred shorter overall survival in multivariate comparisons. These data indicate that additional cytogenetic and mutational abnormalities, and particularly additional trisomies, IGHV status, and TP53 disruption, influence tri12 patient outcomes and could improve risk stratification in this population.
Background: Pediatric low-grade glioma (pLGG) represents the most common brain tumor in childhood. Previous studies have reported that a therapeutic strategy on the basis of the association of bevacizumab alone (B) or in combination with irinotecan (BI) could produce rapid tumor response and clinical improvement in children with pLGG. Nevertheless, a majority of patients relapses shortly (median, 5 mo) after stopping B or BI treatment. We proposed metronomic maintenance with weekly vinblastine added after a 6 months induction of B/BI to prevent early relapse. Patients and Methods: Monocentric retrospective analysis of a patient with pLGG treated with B or BI for 6 months followed by a 12-month maintenance with weekly vinblastine (6 mg/m²) from October 2012 to September 2019 in a single institution. Results: In total, 18 patients (7 males and 11 females) were identified. Because of progression during the B or BI induction 2/18 children were excluded. In total, 16 patients were analyzed with a median age of 10 years (range, 4 to 16 y). A total of 13 patients received BI and 3 patients received B alone. The mean duration of induction was 6.2 months (range, 2 to 12 mo). After induction 5/16 patients had a partial radiologic response, 11/16 patients had stable disease. All patients started maintenance (median duration, 12 mo; range, 3 to 12 mo). With a median follow-up of 3.9 years after the end of B or BI (range, 11 mo to 7.2 y), 15/16 patients were alive and 9/16 patients were progression-free. Seven of 16 children progressed with a median time to progression of 23 months (ranges, 5 to 39 mo). Three of 16 (18%) children progressed during vinblastine maintenance and 4/16 (25%) patients after the end of maintenance. After the total duration of treatment, clinical improvement was noted in 4 patients, 9 patients had stable symptoms, and only 3 patients progressed. One and 2-year event-free survival were, respectively, 81.2% and 56.2%. Two-year overall survival was 93.7%. Conclusions: We report here, the potential benefit and the improvement of progression-free survival by adding metronomic maintenance with weekly vinblastine after initial induction with B or BI in children with low-grade glioma.
Les syndromes myelodysplasiques (SMD) sont un groupe heterogene d’hemopathies clonales, caracterisees par la presence de cytopenies malgre une moelle riche du fait d’une hematopoiese inefficace, et un exces de blastes variable. Il s’agit d’une pathologie du sujet âge. Le risque evolutif est la transformation en leucemie aigue myeloide. De nouveaux marqueurs par cytometrie de flux, et surtout en biologie moleculaire permettent d’affiner le pronostic et la decision therapeutique. Au cours des dix dernieres annees, des avancees therapeutiques liees a l’enregistrement de nouvelles molecules et a l’elargissement de l’eligibilite des patients a l’allogreffe de cellules souches hematopoietiques, ont ameliore la prise en charge des patients atteints de SMD.
L’Allogreffe de Cellules Souches Hematopoietiques a change le pronostic des enfants atteints de Leucemie Aigue. Cependant, la strategie therapeutique apres rechute post allogreffe reste mal definie. Nous avons cherche a comparer les strategies therapeutiques chez 334 enfants atteints de leucemie aigue apres echec d’allogreffe sur une periode recente de dix ans.
Au total, 288 enfants traites dans l’un des 33 centres de la SFGM-TC ont ete analysables (157 Leucemie Aigue Lymphoblastique, 123 Leucemie Aigue Myeloide et 8 biphenotypiques). L’âge median etait de 8,16 ans lors de la premiere allogreffe.
Le delai median entre la premiere allogreffe et la rechute ou progression etait de 182 jours. Les enfants
ont recu 5 traitements differents : a) une chimiotherapie seule (n = 108), b) une chimiotherapie suivie par une deuxieme allogreffe (n = 70), c) des soins palliatifs (n = 67), d)la combinaison d’une chimiotherapie et la reinjection de lymphocytes du donneur (DLI) (n =30), e) la reinjection isolee de DLI (n = 13). La duree mediane de survie apres une rechuteetait de 164 jours et differait en fonction du traitement : DLI + chimiotherapie = 385 jours (j),deuxieme allogreffe = 391j, chimiotherapie seule = 174j, DLI seul = 140j, soins palliatifs =43j.
Une seconde allogreffe ou la combinaison de chimiotherapie + DLI donne des resultats comparables (HR = 0,85, p = 0,53) contrairement a la chimiotherapie seule (HR 1,43 p =0,04), aux soins palliatifs (HR = 4,24, p <0,0001) ou aux DLI seuls (HR = 1,94, p <0,04).
Cette etude montre l’impact positifde l’immunotherapie : la survie la plus prolongee est assuree par une deuxieme allogreffe ou par une combinaison associant chimiotherapie et DLI.
