Online first
Artykuł przeglądowy
Opublikowany online: 2025-02-12
Wyświetlenia strony
29
Wyświetlenia/pobrania artykułu
19
Nowe algorytmy leczenia pierwszej linii dorosłych chorych na ostrą białaczkę limfoblastyczną
1
Streszczenie
Leczenie pierwszej linii dorosłych chorych na ostrą białaczkę limfoblastyczną (ALL, acute lymphoblastic leukemia) zależy od podtypu choroby, profilu prognostycznego oraz wieku i stanu biologicznego pacjenta. W przypadku ALL z linii limfocytów B bez chromosomu Filadelfia (Filadelfia-ujemnej postaci B-ALL) dotychczasowa strategia zakładała stosowanie intensywnej chemioterapii wzorowanej na protokołach pediatrycznych, którą w przypadku wysokiego ryzyka nawrotu choroby uzupełniano transplantacją allogenicznych komórek krwiotwórczych (allo-HCT, allogeneic hematopoietic cell transplantation). W tej grupie chorych nowy standard wyznaczyły wyniki badania ECOG-ARIN E1910, w pełni uzasadniające dołączenie blinatumomabu w sekwencji z chemioterapią konsolidującą. W przypadku Filadelfia-dodatniej postaci B-ALL podstawą terapii jest stosowanie inhibitorów kinazy tyrozynowej, przy czym możliwe jest zredukowanie intensywności chemioterapii. Najlepsze wyniki dotyczą jednak protokołów całkowicie pozbawionych chemioterapii systemowej, w których jest ona zastąpiona stosowaniem blinatumombu. W przypadku ALL z linii limfocytów T, wobec braku dostępnych form immunoterapii, standardem postepowania pozostaje konwencjonalna chemioterapia z lub bez allo-HCT.
Słowa kluczowe: ostra białaczka limfoblastycznaleczenieimmunoterapiablinatumomab
Referencje
- Alaggio R, Amador C, Anagnostopoulos I, et al. International Agency for Research on Cancer/World Health Organization. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms. Leukemia. 2022; 36(7): 1720–1748.
- Arber DA, Orazi A, Hasserjian RP, et al. International Consensus Classification of Myeloid Neoplasms and Acute Leukemias: integrating morphologic, clinical, and genomic data. Blood. 2022; 140(11): 1200–1228.
- Yi M, Zhou L, Li A, et al. Global burden and trend of acute lymphoblastic leukemia from 1990 to 2017. Aging (Albany NY). 2020; 12(22): 22869–22891.
- Gökbuget N, Boissel N, Chiaretti S, et al. Diagnosis, prognostic factors, and assessment of ALL in adults: 2024 ELN recommendations from a European expert panel. Blood. 2024; 143(19): 1891–1902.
- Gökbuget N, Boissel N, Chiaretti S, et al. Management of ALL in adults: 2024 ELN recommendations from a European expert panel. Blood. 2024; 143(19): 1903–1930.
- Siegel SE, Stock W, Johnson RH, et al. Pediatric-inspired treatment regimens for adolescents and young adults with Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia: A review. JAMA Oncol. 2018; 4(5): 725–734.
- Bender C, Maese L, Carter-Febres M, et al. Clinical utility of pegaspargase in children, adolescents and young adult patients with Acute Lymphoblastic Leukemia: a review. Blood Lymphat Cancer. 2021; 11: 25–40.
- Piatkowska-Jakubas B, Krawczyk-Kuliś M, Giebel S, et al. Polish Adult Leukemia Group. Use of L-asparaginase in Acute Lymphoblastic Leukemia: Recommendations of the Polish Adult Leukemia Group. Pol Arch Med Wewn. 2008; 118(11): 664–669.
- Giebel S, Krawczyk-Kuliś M, Adamczyk-Cioch M, et al. Polish Adult Leukemia Group. Prophylaxis and therapy of central nervous system involvement in adult Acute Lymphoblastic Leukemia: Recommendations of the Polish Adult Leukemia Group. Pol Arch Med Wewn. 2008; 118(6): 356–361.
- Giebel S, Labopin M, Socié G, et al. Improving results of allogeneic hematopoietic cell transplantation for adults with Acute Lymphoblastic Leukemia in first complete remission: an analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Haematologica. 2017; 102(1): 139–149.
- Giebel S, Marks DI, Boissel N, et al. Hematopoietic stem cell transplantation for adults with Philadelphia chromosome-negative acute lymphoblastic leukemia in first remission: a position statement of the European Working Group for Adult Acute Lymphoblastic Leukemia (EWALL) and the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplant. 2019; 54(6): 798–809.
- Szczepański T. Why and how to quantify minimal residual disease in acute lymphoblastic leukemia? Leukemia. 2007; 21(4): 622–626.
- van Dongen JJM, van der Velden VHJ, Brüggemann M, et al. Minimal residual disease diagnostics in Acute Lymphoblastic Leukemia: Need for sensitive, fast, and standardized technologies. Blood. 2015; 125(26): 3996–4009.
- Shaver AC, Greig BW, Mosse CA, et al. B-ALL minimal residual disease flow cytometry: an application of a novel method for optimization of a single-tube model. Am J Clin Pathol. 2015; 143(5): 716–724.
- Vidriales MB, Pérez JJ, López-Berges MC, et al. Minimal residual disease in adolescent (older than 14 years) and adult acute lymphoblastic leukemias: early immunophenotypic evaluation has high clinical value. Blood. 2003; 101(12): 4695–4700.
- Holowiecki J, Krawczyk-Kulis M, Giebel S, et al. Status of minimal residual disease after induction predicts outcome in both standard and high-risk Ph-negative adult acute lymphoblastic leukaemia. The Polish Adult Leukemia Group ALL 4-2002 MRD Study. Br J Haematol. 2008; 142(2): 227–237.
- Brüggemann M, Raff T, Flohr T, et al. German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia. Clinical significance of minimal residual disease quantification in adult patients with standard-risk acute lymphoblastic leukemia. Blood. 2006; 107(3): 1116–1123.
- Gökbuget N, Dombret H, Giebel S, et al. Minimal residual disease level predicts outcome in adults with Ph-negative B-precursor acute lymphoblastic leukemia. Hematology. 2019; 24(1): 337–348.
- Shem-Tov N, Peczynski C, Labopin M, et al. Haploidentical vs. unrelated allogeneic stem cell transplantation for acute lymphoblastic leukemia in first complete remission: on behalf of the ALWP of the EBMT. Leukemia. 2020; 34(1): 283–292.
- Nagler A, Labopin M, Houhou M, et al. Outcome of haploidentical versus matched sibling donors in hematopoietic stem cell transplantation for adult patients with acute lymphoblastic leukemia: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. J Hematol Oncol. 2021; 14(1): 53.
- Pavlů J, Labopin M, Niittyvuopio R, et al. Measurable residual disease at myeloablative allogeneic transplantation in adults with acute lymphoblastic leukemia: a retrospective registry study on 2780 patients from the acute leukemia working party of the EBMT. J Hematol Oncol. 2019; 12(1): 108.
- Peters C, Dalle JH, Locatelli F, et al. Total body irradiation or chemotherapy conditioning in childhood ALL: A multinational, randomized, noninferiority phase III study. J Clin Oncol. 2021; 39(4): 295–307.
- Nagler A, Kanate AS, Labopin M, et al. Post-transplant cyclophosphamide versus anti-thymocyte globulin for graft-versus-host disease prevention in haploidentical transplantation for adult acute lymphoblastic leukemia. Haematologica. 2021; 106(6): 1591–1598.
- Giebel S, Labopin M, Salmenniemi U, et al. Posttransplant cyclophosphamide versus antithymocyte globulin in patients with acute lymphoblastic leukemia treated with allogeneic hematopoietic cell transplantation from matched unrelated donors: A study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Cancer. 2023; 129(23): 3735–3745.
- Maury S, Chevret S, Thomas X, et al. for GRAALL. Rituximab in B-Lineage Adult Acute Lymphoblastic Leukemia. N Engl J Med. 2016; 375(11): 1044–1053.
- Marks DI, Kirkwood AA, Rowntree CJ, et al. Addition of four doses of rituximab to standard induction chemotherapy in adult patients with precursor B-cell acute lymphoblastic leukaemia (UKALL14): a phase 3, multicentre, randomised controlled trial. Lancet Haematol. 2022; 9(4): e262–e275.
- Gökbuget N, Dombret H, Bonifacio M, et al. Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood. 2018; 131(14): 1522–1531.
- Aldoss I, Forman SJ, Pullarkat V. Acute Lymphoblastic Leukemia in the Older Adult. J Oncol Pract. 2019; 15(2): 67–75.
- Chiaretti S, Della St, Santoro A, et al. Preliminary results of the GIMEMA LAL2317 sequential chemotherapy-blinatumomab frontline trial for newly diagnosed adult Ph-negative B-lineage ALL patients. Blood. 2023; 142(Supplement 1): 826.
- Boissel N, Huguet F, Leguay T, et al. Blinatumomab during Consolidation in High-Risk Philadelphia Chromosome (Ph)-Negative B-Cell Precursor (BCP) Acute Lymphoblastic Leukemia (ALL) Adult Patients: A Two-Cohort Comparison within the Graall-2014/B Study. Blood. 2022; 140(Supplement 1): 507–509.
- Jabbour E, Short NJ, Jain N, et al. Hyper-CVAD and sequential blinatumomab for newly diagnosed Philadelphia chromosome-negative B-cell acute lymphocytic leukaemia: a single-arm, single-centre, phase 2 trial. Lancet Haematol. 2022; 9(12): e878–e885.
- Stelljes M, Raffel S, Alakel N, et al. Inotuzumab Ozogamicin as Induction Therapy for Patients Older Than 55 Years With Philadelphia Chromosome-Negative B-Precursor ALL. J Clin Oncol. 2024; 42(3): 273–282.
- Chevallier P, Leguay T, Delord M, et al. Inotuzumab Ozogamicin and Low-Intensity Chemotherapy in Older Patients With Newly Diagnosed CD22 + Philadelphia Chromosome–Negative B-Cell Precursor Acute Lymphoblastic Leukemia. J Clin Oncol. 2024; 42(36): 4327–4341.
- Goekbuget N, Stoltefuß A, Topp M, et al. Dose reduced chemotherapy in sequence with blinatumomab for newly diagnosed older patients with b-precursor adult lymphoblastic leukemia (ALL): Results of the ongoing GMALL bold trial. Blood. 2021; 138(Supplement 1): 3399–3399.
- Robak T, Szmigielska-Kapłon A, Wrzesień-Kuś A, et al. Acute lymphoblastic leukemia in elderly: the Polish Adult Leukemia Group (PALG) experience. Ann Hematol. 2004; 83(4): 225–231.
- Litzow MR, Sun Z, Mattison RJ, et al. Blinatumomab for MRD-Negative Acute Lymphoblastic Leukemia in Adults. N Engl J Med. 2024; 391(4): 320–333.
- Burmeister T, Schwartz S, Bartram CR, et al. GMALL study group. Patients' age and BCR-ABL frequency in adult B-precursor ALL: a retrospective analysis from the GMALL study group. Blood. 2008; 112(3): 918–919.
- Thomas DA, Faderl S, Cortes J, et al. Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood. 2004; 103(12): 4396–4407.
- de Labarthe A, Rousselot P, Huguet-Rigal F, et al. Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL). Imatinib combined with induction or consolidation chemotherapy in patients with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia: results of the GRAAPH-2003 study. Blood. 2007; 109(4): 1408–1413.
- Chiaretti S, Foà R. How I treat adult Ph+ ALL. Blood. 2025; 145(1): 11–19.
- Chalandon Y, Thomas X, Hayette S, et al. Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL). Randomized study of reduced-intensity chemotherapy combined with imatinib in adults with Ph-positive acute lymphoblastic leukemia. Blood. 2015; 125(24): 3711–3719.
- Giebel S, Czyz A, Ottmann O, et al. Use of tyrosine kinase inhibitors to prevent relapse after allogeneic hematopoietic stem cell transplantation for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: A position statement of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Cancer. 2016; 122(19): 2941–2951.
- Shen S, Chen X, Cai J, et al. Effect of dasatinib vs imatinib in the treatment of pediatric philadelphia chromosome-positive acute lymphoblastic leukemia: A randomized clinical trial. JAMA Oncol. 2020; 6(3): 358–366.
- Jabbour E, Kantarjian HM, Aldoss I, et al. Ponatinib vs imatinib in frontline philadelphia chromosome-positive acute lymphoblastic leukemia: A randomized clinical trial. JAMA. 2024; 331(21): 1814–1823.
- Foà R, Bassan R, Vitale A, et al. GIMEMA Investigators. Dasatinib-Blinatumomab for Ph-Positive Acute Lymphoblastic Leukemia in Adults. N Engl J Med. 2020; 383(17): 1613–1623.
- Jabbour E, Short NJ, Jain N, et al. Ponatinib and blinatumomab for Philadelphia chromosome-positive acute lymphoblastic leukaemia: a US, single-centre, single-arm, phase 2 trial. Lancet Haematol. 2023; 10(1): e24–e34.
- Advani AS, Moseley A, O'Dwyer KM, et al. Dasatinib/prednisone induction followed by blinatumomab/dasatinib in Ph+ acute lymphoblastic leukemia. Blood Adv. 2023; 7(7): 1279–1285.
- Foà R, Bassan R, Elia L, et al. Long-Term Results of the Dasatinib-Blinatumomab Protocol for Adult Philadelphia-Positive ALL. J Clin Oncol. 2024; 42(8): 881–885.
- Ghobadi A, Slade M, Kantarjian H, et al. The role of allogeneic transplant for adult Ph+ ALL in CR1 with complete molecular remission: a retrospective analysis. Blood. 2022; 140(20): 2101–2112.
- Nishiwaki S, Sugiura I, Fujisawa S, et al. Japan Adult Leukemia Study Group. Utility of allogeneic stem cell transplantation for adult Ph+ALL with complete molecular remission. Am J Hematol. 2024; 99(5): 806–815.
- Kim R, Chalandon Y, Rousselot P, et al. Significance of Measurable Residual Disease in Adult Philadelphia Chromosome-Positive ALL: A GRAAPH-2014 Study. J Clin Oncol. 2024; 42(26): 3140–3150.
- Rowntree C, Kirkwood A, Clifton-Hadley L, et al. First analysis of the UKALL14 randomized trial to determine whether the addition of nelarabine to standard chemotherapy improves event free survival in adults with t-cell acute lymphoblastic leukaemia (CRUK/09/006). Blood. 2021; 138(Supplement 1): 366–366.
- Morita K, Jain N, Kantarjian H, et al. Outcome of T-cell acute lymphoblastic leukemia/lymphoma: Focus on near-ETP phenotype and differential impact of nelarabine. Am J Hematol. 2021; 96(5): 589–598.
- Sebastian G. How I treat newly diagnosed acute lymphoblastic leukemia. Clin Hematol Int. 2024; 6(2): 51–61.
