Significance of Measurable Residual Disease in Adult Philadelphia Chromosome–Positive ALL: A GRAAPH-2014 Study Article Swipe

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Rathana Kim , Yves Chalandon , Philippe Rousselot , Jean‐Michel Cayuela , Françoise Huguet , Marie Balsat , Marie Passet , Patrice Chevallier , Yosr Hicheri , Emmanuel Raffoux , Thibaut Leguay , Sylvain Chantepie , Sébastien Maury , Sandrine Hayette , Françoise Solly , Thorsten Braun , Bernard De Prijck , Victoria Cacheux , Célia Salanoubat , Laure Farnault , Isabelle Guibaud , Mathilde Lamarque , Lauris Gastaud , Emilie Lemasle , Éolia Brissot , Emmanuelle Tavernier , Karine Bilger , Alban Villate , Jean Soulier , Carlos Graux , Véronique Lheritier , Hervé Dombret , Nicolas Boissel , Emmanuelle Clappier ·

YOU? · · 2024 · Open Access · · DOI: https://doi.org/10.1200/jco.24.00108

PURPOSE BCR::ABL1 quantification is widely regarded as the standard for monitoring measurable residual disease (MRD) in Philadelphia chromosome–positive (Ph+) ALL. However, recent evidence of BCR::ABL1 multilineage involvement questions the significance of BCR::ABL1 MRD. We aimed to define the prognostic role of MRD as assessed by BCR::ABL1 or lymphoid-specific immunoglobulin/T-cell receptor ( IG/TR) gene markers. PATIENTS AND METHODS We conducted BCR::ABL1 and IG/TR quantification after each treatment cycle in 264 patients treated in the GRAAPH-2014 trial, which used four cycles of reduced-intensity chemotherapy with nilotinib, followed by hematopoietic stem-cell transplantation (HSCT). RESULTS Comparing BCR::ABL1 and IG/TR MRD revealed residual BCR::ABL1-positive non-ALL cells in 98 (43%) of 228 patients, defining multilineage Ph+ ALL. Despite poorer BCR::ABL1 responses, patients with multilineage Ph+ ALL had similar disease-free survival (DFS; hazard ratio [HR], 0.83 [95% CI, 0.49 to 1.41]; P = .50). Although BCR::ABL1 response failed to predict outcomes, IG/TR positivity (≥0.01%) was strongly associated with lower DFS (after cycle 2, HR, 2.49 [95% CI, 1.40 to 4.40]; P = .002; after cycle 4, HR, 4.13 [95% CI, 1.82 to 9.38]; P = .001). In multivariable analysis, both IG/TR positivity after cycle 2 and initial WBC count ≥30 × 10 9 /L predicted poorer DFS, enabling to define a high-risk group having a 4-year DFS of 56.5% compared with 87.6% (HR, 3.72 [95% CI, 1.93 to 7.15]; P < .001). Moreover, allogeneic HSCT significantly improved DFS in the high-risk group (HR, 0.33 [95% CI, 0.18 to 0.60]; P < .001), whereas the standard-risk group had favorable outcomes regardless of allogeneic HSCT. CONCLUSION Our findings challenge the significance of BCR::ABL1 monitoring in adult Ph+ ALL and demonstrate the prognostic role of IG/TR MRD. This study provides a framework for using MRD to guide treatment strategies in adults with Ph+ ALL.

Related Topics

Medicine

Internal Medicine

Oncology

Hematopoietic Stem Cell Transplantation

Immunology

Leukemia

Concepts

Medicine Hazard ratio Internal medicine Minimal residual disease Oncology Hematopoietic stem cell transplantation Gastroenterology Immunology Transplantation Confidence interval Leukemia

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Type: article
Language: en
Landing Page: https://doi.org/10.1200/jco.24.00108
OA Status: green
Cited By: 27
References: 29
Related Works: 10
OpenAlex ID: https://openalex.org/W4400805570

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OpenAlex ID: https://openalex.org/W4400805570

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DOI: https://doi.org/10.1200/jco.24.00108

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Title: Significance of Measurable Residual Disease in Adult Philadelphia Chromosome–Positive ALL: A GRAAPH-2014 Study

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Type: article

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Language: en

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Publication year: 2024

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Publication date: 2024-07-19

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Authors: Rathana Kim, Yves Chalandon, Philippe Rousselot, Jean‐Michel Cayuela, Françoise Huguet, Marie Balsat, Marie Passet, Patrice Chevallier, Yosr Hicheri, Emmanuel Raffoux, Thibaut Leguay, Sylvain Chantepie, Sébastien Maury, Sandrine Hayette, Françoise Solly, Thorsten Braun, Bernard De Prijck, Victoria Cacheux, Célia Salanoubat, Laure Farnault, Isabelle Guibaud, Mathilde Lamarque, Lauris Gastaud, Emilie Lemasle, Éolia Brissot, Emmanuelle Tavernier, Karine Bilger, Alban Villate, Jean Soulier, Carlos Graux, Véronique Lheritier, Hervé Dombret, Nicolas Boissel, Emmanuelle Clappier

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Landing page: https://doi.org/10.1200/jco.24.00108

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Open access: Yes

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OA status: green

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OA URL: https://hdl.handle.net/2078.1/290100

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Concepts: Medicine, Hazard ratio, Internal medicine, Minimal residual disease, Oncology, Hematopoietic stem cell transplantation, Gastroenterology, Immunology, Transplantation, Confidence interval, Leukemia

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Cited by: 27

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Citations by year (recent): 2025: 22, 2024: 5

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References (count): 29

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Related works (count): 10

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