Persistence of lymphoblasts in bone marrow on day 15 and days 22 to 25 of remission induction predicts a dismal treatment outcome in children with acute lymphoblastic leukemia

Abstract

We determined the prognostic importance of morphologically identifiable persistent disease at day 15 and days 22 to 25 of remission induction in childhood acute lymphoblastic leukemia (ALL). Among 546 patients entered on 2 consecutive protocols, 397 patients had evaluable bone marrow (BM) examinations on day 15 (؎ 1 day) and 218 on days 22 to 25 (؎ 1 day). Fifty-seven patients (14%) had persistent lymphoblasts (> 1%) in the BM on day 15 and 27 patients (5.5%) had persistent lymphoblasts on days 22 to 25. The 5-year event-free survival (EFS) was significantly worse for patients with lymphoblasts on day 15 (40% ؎ 6%) or on days 22 to 25 (4% ؎ 3%) as compared to those without lymphoblasts on these dates (78% ؎ 2% and 76% ؎ 2%, respectively, P < .001 for both comparisons). A worse prognosis was observed even for patients with a low percentage of lymphoblasts (ie, 1%-4%) at either day 15 (5-year EFS ‫؍‬ 56% ؎ 8%) or days 22 to 25 (5-year EFS ‫؍‬ 0%) compared to those without morphologically identifiable persistent lymphoblasts at these times (P < .001 for both comparisons). The prognostic impact of persistent lymphoblasts on both dates remained significant after adjusting for other known risk factors, including treatment protocol, age, white blood cell count, DNA index, cell lineage, and central nervous system status, and National Cancer Institute/ Rome criteria simultaneously. Hence, persistence of lymphoblasts (even 1%-4%) on day 15 of remission induction was associated with a poor prognosis and on days 22 to 25 signified a particularly dismal outcome; these very highrisk patients require novel or more intensive therapy to improve outcome. (Blood. 2002;100:43-47)

Antimetabolite therapy for lesser-risk B-lineage acute lymphoblastic leukemia of childhood: a report from Children's Oncology Group Study P9201

“…This supports multiple prior observations regarding the prognostic value of early response, whether measured by peripheral blasts on day-8 or day-15 bone marrow aspiration. 11,12 In this study, only 9 patients had more than 100 blasts/L at day 8, too few to allow meaningful statistical analysis, although 2 of these 9 patients have relapsed.…”

“…This supports multiple prior observations regarding the prognostic value of early response, whether measured by peripheral blasts on day-8 or day-15 bone marrow aspiration. 11,12 In this study, only 9 patients had more than 100 blasts/L at day 8, too few to allow meaningful statistical analysis, although 2 of these 9 patients have relapsed.There were no statistically significant differences in EFS based upon sex, CNS status, ethnicity, or initial WBC value (Ͻ 10 ϫ 10 9 /L versus 10-50 ϫ 10 9 /L [Ͻ 10 000 /L versus 10 000-50 000 /L]). The great majority of patients on this study were CNS1 (595/649 or 91.7%).…”

Tolerance and efficacy of autologous or donor-derived T cells expressing CD19 chimeric antigen receptors in adult B-ALL with extramedullary leukemia

“…Moreover, leukemia infiltration into extramedullary sites may also reduce leukemia responsiveness to induction chemotherapy, 3,4 whereas persisting blasts correlate with decreased overall survival and confer poor prognosis in patients with ALL. 5,6 For this reason, new therapeutic regimens for this patient population are needed.…”

Prediction of outcome by early bone marrow response in childhood acute lymphoblastic leukemia treated in the ALL-BFM 95 trial: differential effects in precursor B-cell and T-cell leukemia

“…[14][15][16][17][18][19] The St. Jude Total Therapy Study Group showed that even the persistence of low percentages (1-4%) of BM lymphoblasts on Day 15 (corresponding to Day 22 of the BFM protocol without prednisone prephase) and Days 22 to 25 of induction therapy was associated with a significantly poorer 5-year event free survival rate compared to patients without detectable BM blasts (40±6% vs. 78±2%). 20 In the ALL-BFM 95 trial, cytomorphological response in BM on Day 15 (BMd15) was prospectively assessed without being used for risk stratification. In the present study, the prognostic value of BMd15 in ALL-BFM 95 was evaluated in comparison and combined with PR, cytomorphological BM response to induction therapy (Day 33), age and white blood cell count (WBC) at diagnosis; all factors included in the ALL-BFM 95 risk stratification.…”