Single Centre, Retrospective Analysis of Treatment Outcomes and Prognostic Factors in Blastic Phase Chronic Myeloid Leukemia (CML-BP) Following Systemic Therapy
Notice bibliographique
Résumé
Introduction: Despite the introduction of BCR-ABL1 tyrosine kinase inhibitors (TKI), the prognosis of blastic phase chronic myeloid leukemia (CML-BP) remains dismal. Due to its low incidence, prospective evaluation of outcomes of CML-BP following systemic treatment is challenging. Thus, we aimed to evaluate the outcomes of CML-BP following systemic therapy, and to analyze prognostic factors affecting treatment outcomes. Methods: We retrospectively identified 55 patients with CML-BP per the European LeukaemiaNet 2013 criteria who treated at the Princess Margaret Cancer Centre in Toronto, Canada between 2000 and 2022. Patient and disease characteristics at the time of CML-BP diagnosis are presented in Table 1. Multiparametric flow cytometry data are described below, with percentages reflecting the proportion of positive antigen expression in evaluable patients. Treatment outcomes measured included: complete response (CR), leukaemia-free survival (LFS) and overall survival (OS). Prognostic factors evaluated include: age, transformation from chronic/accelerated phase (CP/AP), clonal evolution (CE), additional cytogenetic abnormalities (ACA), ABL1 KD mutation, extramedullary disease, blast immunophenotype, systemic treatment modality (intensive chemotherapy (IC) +/- TKI vs TKI monotherapy) and allogeneic haematopoietic stem cell transplantation (HCT). Results: Among the 55 patients, the median age at time of CML-BP diagnosis was 45 years (17 - 68) and included 35 (64%) cases of CML in myeloid BP (MBP) and 20 (36%) cases of lymphoid BP (LBP). 40 (72%) patients had transformed from a previous CP/AP with a median time of 2.4 years (0.1 - 19.3) from initial diagnosis to transformation. Extramedullary disease was present in 18/53 (34%) patients. The blast immunophenotype of MBP patients (n=31) was: CD34+ (84%), CD117+ (52%), HLA-DR+ (68%), CD13+ (87%), CD33+ (97%), MPO+ (40%), CD38+ (100%) and CD123+ (50%). Nine MBP patients (36%) had aberrant CD7 expression. Among 17 evaluable LBP patients, the immunophenotypic profile was: CD34+ (94%), HLA-DR+ (76%), CD19+ (94%), CD20+ (41%), CD10+ (94%), TdT (88%), CD38+ (100%) and CD7+ (18%). Nine patients (53%) had aberrant CD13 expression and five (29%) displayed aberrant CD33 expression. At CML-BP diagnosis, 21/42 (50%) had an ACA, of which 11 (26%) patients had high risk ACA, defined as −7/7q, 11q23 or 3q26.2 aberrations, or complex karyotype. Among transformed patients, CE was present in 16/43 (37%) patients. In 18 patients evaluated with Sanger sequencing at time of BP transformation, 9 patients (50%) had an ABL1-KD mutation. 54/55 received systemic therapy: 31 (57%) intensive chemotherapy (IC) + TKI, 7 (13%) IC alone, and 16 (30%) TKI monotherapy. Two patients died before response assessment, one after IC and one after TKI monotherapy. Among 46 patients with available post-treatment bone marrow assessments, CR/CRi rates were similar in those treated with IC+ TKI (29/31; 94%), IC only (5/6; 83%) or TKI only (7/9; 78%). Overall, 40/54 (74%) patients proceeded to allogeneic HCT after achieving CR/CRi or second CP. After a median follow-up of 39 months, the 3-year LFS and OS rates of all patients were 34.9% (20.7-49.6%) and 44.9% (95% CI, 30.4-58.4%), respectively. Patients with CML-LBP had a significantly higher OS compared to those with CML-MBP (p=0.0463), however, no significant difference in LFS was seen (p= 0.0913). Median duration of LFS and OS was 1.56 and 2.51 years, respectively. The following variables were found to be independently prognostic for OS: Transformation from CP/AP (p=0.0489, HR 4.328 [1.007, 18.60]), CD117 expression at time of CML-BP (p=0.0291, HR 2.809 [1.111, 7.102]), and IC + TKI (vs TKI monotherapy) (p=0.0068, HR 0.268 [0.104, 0.689]). CE at BP, transformation from CP/AP and IC +TKI (vs TKI monotherapy) were prognostic for LFS by univariate analysis, however, none was identified as independent risk factors. Conclusion The prognosis of CML-BP remains poor despite systemic therapy. Transformation from CP/AP, CD117 positivity at diagnosis of CML-BP and TKI monotherapy were identified as independent, adverse prognostic risk factors for OS. However, treatment with IC + TKI appeared to improve survival outcomes compared with TKI therapy alone. Therefore, combination therapy with IC + TKI should be considered the optimal strategy in treatment patients with CML-BP. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,001 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».