Main Article Content

Matteo Parma
Clara Vigano'
Monica Fumagalli
Federica Colnaghi
Arianna Colombo
Federica Mottadelli
Vincenzo Rossi
Elena Elli
Elisabetta Terruzzi
Angelo Belotti
Giovanni Cazzaniga
Enrico Maria Pogliani
Pietro Pioltelli


Acute Lymphoblastic Leukemia, Bone marrow transplantation, Minimal Residual Disease


Background and Objectives: Acute lymphoblastic leukaemia (ALL) carrying t(9;22) or t(4;11) genetic abnormalities represents a very high risk subtype of disease (VHR-ALL). Hematopoietic stem cell transplantation (HSCT) still remains the only curative option also in the Imatinib era. In the last years low molecular level of minimal residual disease (MRD) before HSCT was reported as one of the best favourable indexes for survival in ALL. Here we observed that even these patients can show a favourable outcome, if submitted to HSCT with very low MRD. Methods: We considered 18 consecutive VHR-ALL patients eligible to HSCT. 16 of them were transplanted upon first remission, as soon as possible, employing myelo-ablative conditioning regimens. Molecular MRD has been evaluated before and after HSCT.Results: Immediately before HSCT MRD revealed: complete molecular remission (MRDneg) for 5 patients and a level <1x10-3 for 7 patients; 100 days after HSCT we had: MRDneg for 7 patients and a decrease for all the others after HSCT. After tapering of immunosuppressive drugs, 13 patients reached the MRDneg in a median time of 8 months (range 3-16); Based on intention to treat analysis: 14/18 patients are alive and disease free at the time of analysis, overall survival and event free survival is of 78% and 66% respectively, with an average follow-up of 45 months (range 6-84) since HSCT. Conclusion: Early transplantation with low MRD level seems to be correlated with a favourable outcome also in VHR-ALL


Download data is not yet available.

Abstract 1801
PDF Downloads 818
HTML Downloads 1141


[1] Ferrando AA, Look AT. Clinical implications of recurring chromosomal and associated molecular abnormalities in acute lymphoblastic leukemia, Semin Hematol 2000; 37: 381-395.

[2] Moorman AV; Chilton L, Wilkinson J, Ensor HM, Bown N, Proctor SJ. A population-based cytogenetic study of adults with acute lymphoblastic leukaemia. Blood 2010; 115: 206-214.

[3] Marchesi F, Girardi K, Avvisati G. Pathogenetic, clinical and prognostic features of adult t(4;11)(q21q23)/MLL-AF4 positive B cell acute lymphoblastic leukemia. Advances in Hematology 2011; ID 621627.

[4] Gleissner B, Goekbuget N, Rieder H, Arnold R, Schwartz S, Diedrich H, Schoch C, Heinze B, Fonatsch C, Bartram CR, Hoelzer D. CD10- pre-B acute lymphoblastic leukemia (ALL) is a distinct high-risk subgroup of adult ALL associated with a high frequency of MLL aberrations: results of the German Multicenter Trials for Adult ALL (GMALL). Blood 2005; 106: 4054-4056.

[5] Bertrand FE, Vogtenhuber C, Shah N, Le Bien TW. Pro–B-cell to pre-B-cell development in B-lineage acute lymphoblastic leukemia expressing the MLL/AF4 fusion protein. Blood 2001; 98: 3398-3405.

[6] Markx DI, Moorman AV, Chilton L, Paletta E, Enshaie A, DeWald G, Harrison CJ, Fielding AK, Foroni L, Goldstone AH, Litzow MR, Luger SM, McMillan AK, Racevskis J, Rowe JM, Tallman MS, Wiernik P, Lazarus HM. The clinical characteristics, therapy and outcome of 85 adults with acute lymphoblastic leukemia and t(4;11)(q21q23)/MLL-AFF1 prospectively treated in the UKALLXII/ECOG2993 trial. Haematologica 2013; 98: 945-952.

[7] Vey N, Thomas X, Picard C, Kavascovicz T, Charin C, Cayuela JM, Dombret H, Dastugue N, Huguet F, Bastard C, Stamatoulas A, Giollant M, Tournilhac O, Macintyre E, Buzyn A, Bories D, Kuentz M, Dreyfus F, Delannoy A, Raynaud S, Gratecos N, Bordessoule D, de Botton S, Preudhomme C, Reman O, Troussard X, Pigneux A, Bilhou C, Vernant JP, Boucheix C, Gabert J. Allogeneic stem cell transplantation improves the outcome of adults with t(1;19)/E2A-PBX1 and t(4;11)/MLL-AF4 positive B-cell acute lymphoblastic leukemia: results of the prospective multicenter LALA-94 study. Leukemia 2006; 20: 2155-2161.

[8] Ljungman P, Bregni M, Brune M, Cornelissen J, de Witte T, Dini G Einsele H, Gaspar HB, Gratwohl A, Passweg J, Peters C, Rocha V, Saccardi R, Schouten H, Sureda A, Tichelli A, Velardi A, Niederwieser D. Allogeneic and autologous transplantation for hematological disease, solid tumors and immune disorders: current practice in Europe. Bone Marrow Transplantation, 2010; 45: 219-234.

[9] Bassan R, Rossi G, Pogliani EM, Di Bona E, Angelucci E, Cavattoni I, Lambertenghi-Deliliers G, Mannelli F, Levis A, Ciceri F, Mattei D, Borlenghi E, Terruzzi E, Borghero C, Romani C, Spinelli O, Tosi M, Oldani E, Intermesoli T, Rambaldi A. Chemotherapy-phased Imatinib pulses improve long-term outcome of adult patient with Philadelphia chromosome-positive acute lymphoblastic leukaemia: Northern Italy Leukemia Group Protocol 09/00. J. Clin. Oncol. 2010; 22: 3644-3651.

[10] Fielding AK, Rowe JM, Buck G, Foroni L, Gerrard G, Litzow MR, Lazarus H, Luger SM, Marks DI, McMillan AK, Moorman AV, Patel B, Paietta E, Tallman MS, Goldstone AH. UKALLXII/ECOG2993: addition of Imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia. Blood 2014; 123: 843-850.

[11] Pinana JL, Sanz J, Picardi A, Ferrà C, Martino R, Barba P Gonzalez-Vicent M, Pascual MJ, Martín C, Verdeguer A, de Heredia CD, Montesinos P, Ribera JM, Sanz M, Arcese W, Sanz G. Umbilical cord blood transplantation from unrelated donors in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Haematologica 2014; 99: 378-384.

[12] Bassan R, Spinelli O, Oldani E, Intermesoli T, Tosi M, Peruta B Rossi G, Borlenghi E, Pogliani EM, Terruzzi E, Fabris P, Cassibba V, Lambertenghi-Deliliers G, Cortelezzi A, Bosi A, Gianfaldoni G, Ciceri F, Bernardi M, Gallamini A, Mattei D, Di Bona E, Romani C, Scattolin AM, Barbui T, Rambaldi A. Improved risk classification for risk specific therapy-based on the molecolar study of minimal residual disease (MRD) in adult acute lymphoblastic leukemia. Blood 2009; 113: 4153-4169.

[13] Cortes JE, Kim DW, Pinilla-Ibartz J, le Coutre P, Paquette R, Chuah C Nicolini FE, Apperley JF, Khoury HJ, Talpaz M, DiPersio J, DeAngelo DJ, Abruzzese E, Rea D, Baccarani M, Müller MC, Gambacorti-Passerini C, Wong S, Lustgarten S, Rivera VM, Clackson T, Turner CD, Haluska FG, Guilhot F, Deininger MW, Hochhaus A, Hughes T, Goldman JM, Shah NP, Kantarjian H. A Phase 2 trial of Ponatinib in Philadelphia Chromosome positive Leukemias. N Engl J Med 2013; 369: 1783-1769.

[14] Gabert J, Beillard E, van der Velden VHJ, Bi W, Grimwade D, Pallisgaard N, Barbany G, Cazzaniga G, Cayuela JM, Cavé H, Pane F, Aerts JL, De Micheli D, Thirion X, Pradel V, González M, Viehmann S, Malec M, Saglio G, van Dongen JJ. Standardization and quality control studies of ’real-time’ quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia- A Europe Against Cancer Program. Leukemia 2003;17: 2318-2357.

[15] Van Dongen JJM, Macintyre EA, Gabert JA, Delabesse E, Rossi V, Saglio G Gottardi E, Rambaldi A, Dotti G, Griesinger F, Parreira A, Gameiro P, Diáz MG, Malec M, Langerak AW, San Miguel JF, Biondi A. Standardized RT-PCR analysis of fusion gene transcripts from chromosome aberrations in acute leukemia for detection of minimal residual disease. Leukemia 1999; 13:1901-1928.

[16] Biondi A, Rambaldi A, Rossi V, Elia L, Caslini C, Basso G, Battista R, Barbui T, Mandelli F and Masera G. Detection of ALL-1/AF4 fusion transcript by reverse polymerase chain reaction for diagnosis and monitoring of acute leukemias with the t(4;11) translocation. Blood 1993; 82: 2943-2947.

Similar Articles

1 2 > >> 

You may also start an advanced similarity search for this article.