Marks, David I;
Moorman, Anthony V;
Chilton, Lucy;
Paietta, Elisabeth;
de Wald, Gordon;
Fielding, Adele K;
Goldstone, Anthony H.;
Litzow, Mark R;
Luger, Selina M.;
McMillan, Andrew;
Rowe, Jacob M.;
Tallman, Martin S;
Lazarus, Hillard M.
Biology and Outcome of 85 Adults with Acute Lymphoblastic Leukemia (ALL) with t(4;11)/MLL-AF4 Treated in the UKALL XII/ECOG 2993 Study
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Media type:
E-Article
Title:
Biology and Outcome of 85 Adults with Acute Lymphoblastic Leukemia (ALL) with t(4;11)/MLL-AF4 Treated in the UKALL XII/ECOG 2993 Study
Contributor:
Marks, David I;
Moorman, Anthony V;
Chilton, Lucy;
Paietta, Elisabeth;
de Wald, Gordon;
Fielding, Adele K;
Goldstone, Anthony H.;
Litzow, Mark R;
Luger, Selina M.;
McMillan, Andrew;
Rowe, Jacob M.;
Tallman, Martin S;
Lazarus, Hillard M.
Description:
<jats:title>Abstract</jats:title>
<jats:p>Abstract 663</jats:p>
<jats:sec>
<jats:title>Introduction:</jats:title>
<jats:p>The biology and outcome of adult t(4;11) ALL are poorly understood. We report here 85 patients treated uniformly on the prospective trial (UKALL XII/ECOG 2993) with the aim of describing outcome and identifying prognostic factors and optimal therapy.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Patients and methods:</jats:title>
<jats:p>1914 adult patients (≥15 years) with ALL were registered on the UKALL XII/ECOG 2993 study in the UK or United States from 1993–2006. Cell lineage was classified by local institutions (UK) or central immunophenotyping (ECOG). Cytogenetic, FISH and RT-PCR analyses of pre-treatment samples were either performed locally and reviewed centrally or performed centrally.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Results:</jats:title>
<jats:p>The 85 patients with t(4;11) were predominantly female (68%). Median age was 38 years (vs 32 years in the non-t(4;11) group) and 42% were >40 years. They had high white cell counts with 87% >30 and 66% >100 × 109/l (vs 7% in the non-t(4;11) group).</jats:p>
<jats:p>Among the 27 ECOG patients, 22 (81%) had the typical pro-B (CD10NEG) immunophenotype, compared to 12% in t(4;11)NEG patients. Aside from expression of myeloid antigens, CD65 and CD15, which is part of the pro-B immunophenotype, t(4;11)POS lymphoblasts showed a unique combination of stem cell antigens: lower expression of CD34 and CD105, but higher expression of CD133 and CD135 compared to t(4;11)NEG blasts (p<0.0001).</jats:p>
<jats:p>Additional cytogenetic abnormalities (ACAs) were present in 31/75 (41%) evaluable cases. Most common ACAs were gain of chromosome X (n=13), i(7)(q10) (n=7) and abnormalities of 1p (n=4). Deletion of IKZF1 or CDKN2A/B was present in 18% of patients tested; neither affected outcome.</jats:p>
<jats:p>Seventy seven evaluable patients attained complete remission (CR1, 93%). Treatment received in CR1 was either chemotherapy (n=46, 59%) or a myeloablative allograft (N=31, 16 matched sibling, 1 mismatched related and 15 unrelated donors UD). CR1 treatment received strongly correlated with age with the number of allografts decreasing with age: <25 years 12/17 patients; 24–39 years 13/29 and 40+ years 6/31 (p=0.001).</jats:p>
<jats:p>At median follow up of 5.4 years, five year EFS was 34% (24–44%, 95% CI) and OS 35% (25–45%). Five year relapse rate was 45% (33–58%); only 1 relapsed patient survived, nearly all events had occurred by 2 years. The 46 patients who received chemotherapy had 24% survival and 69% relapsed but 5 year OS of patients who had sibling or UD allografts was 56% and 67% respectively (p=0.013) and only 3/31 relapsed. An allograft improved OS, EFS and relapse in the <40 year group. Age was also strongly associated with outcome (figure).</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Conclusions:</jats:title>
<jats:p>This is the largest series of adult t(4;11) ALL patients treated uniformly. Allograft in CR1 from sibling or unrelated donors is an effective strategy. Current prospective trials of intensive pediatric-type regimens in younger patients will determine if CR1 allografts are necessary. Older patients have a poor outcome and different strategies such as reduced intensity allografting should be explored.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Disclosures:</jats:title>
<jats:p>No relevant conflicts of interest to declare.</jats:p>
</jats:sec>