Importance of the day 7 bone marrow biopsy as a prognostic measure of the outcome in children with acute lymphoblastic leukemia

Schultz, Kirk R.; Massing, Bonnie G.; Spinelli, John J.; Gaynon, Paul S.; Wadsworth, Louis D.

doi:10.1002/(sici)1096-911x(199707)29:1<16::aid-mpo3>3.0.co;2-v

Cited by 26 publications

(14 citation statements)

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“…In approximately 50% of these cases (both at day 15 and day [22][23][24][25], the percentage of lymphoblasts was less than 5% (ie, 1%-4%). The 6% frequency of 5% lymphoblasts or more on day 15 in our study is similar to the 8% frequency on day 14, reported by CCG (study 105) for average-risk patients receiving similar 4-drug induction therapy.…”

Section: Discussionmentioning

confidence: 96%

“…[21][22][23][24][25][26][27][28][29] For example, in a Berlin-Frankfurt-Münster (BFM) trial, a blast cell count of 1000/L or more in the peripheral blood after a 7-day exposure of prednisone and one intrathecal dose of methotrexate identified a group of patients with a significantly worse prognosis. In a subsequent trial, this group of patients was targeted for more aggressive therapy.…”

Section: Introductionmentioning

confidence: 99%

“…27 Others have assessed the bone marrow (BM) lymphoblast percentage to assess early response to therapy. [22][23][24][25][26]28,29 The Children's Cancer Group (CCG) has examined the prognostic importance of persistent lymphoblasts on day 7 and day 14 of a 4-or 5-drug induction therapy for patients with high-risk ALL (presence of lymphomatous features). They found that among high-risk cases, the day 7 result had greater prognostic impact than the day 14 result; although the day 14 result provided additional information regarding the prognosis of the day 7 slow responders.…”

Section: Introductionmentioning

confidence: 99%

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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

Sandlund

Harrison

Rivera

et al. 2002

Blood

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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)

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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

Sandlund

Harrison

Rivera

et al. 2002

Blood

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“…7 A baseline leucocytosis 450 G/l, a patient's age of less than 12 months or the presence of at least one risk factor (poor response to 7-day prednisone treatment: a decrease in peripheral blood blasts by less than 50%, a delayed start of remission and translocations) allocate a child to a high-risk (HR) group. [8][9][10] The treatment protocol for the HR group patients (New York II scheme) 11 is quite different from that of the LR group (ALL-BFM-90 programme). 12 Despite extensive recognition of the molecular bases of bone marrow proliferative diseases, the mechanisms responsible for disease progression need further investigation.…”

Section: Introductionmentioning

confidence: 99%

Substance P – a potent risk factor in childhood lymphoblastic leukaemia

Nowicki

B²

2003

Leukemia

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The study focused on determining the expression of substance P (SP) in neoplastic bone marrow cells in childhood acute lymphoblastic leukaemia (ALL) in terms of its mRNA and the level of protein production. An attempt has also been made to demonstrate a correlation of SP with leukaemia risk factors and treatment failure. The study group comprised 120 children treated for ALL. Expression of SP was examined by in situ hybridisation with a 5 0 -biotinylated probe and by immunocytochemistry with specific anti-human SP antibody. Out of 80 patients with common ALL, the expression of SP was demonstrated in 33 cases (41.2%). In the group of 24 children with pre-B ALL, the presence of SP was noted in six cases (25.0%). Of 16 patients with T-cell leukaemia, SP expression was demonstrated in 13 cases (81.2%). The percentage of immunopositive cells in the SP-positive cases ranged from 79.8 to 97.3. Treatment failure in the children with ALL was closely related to the expression of SP observed at the beginning of treatment. The results showed a connection between the presence of SPpositive blasts and leukaemia relapse. This may indicate that SP expression, involved in the proliferation of the tumour cells, may represent a novel risk factor in ALL.

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“…[6][7][8][9] Assays for minimal residual disease (MRD) can extend the usefulness of this prognostic factor by measuring the initial response to therapy in patients who have achieved complete remission by morphologic standards. The potential clinical value of these assays was conclusively demonstrated by recently reported prospective studies showing that levels of MRD during clinical remission are strongly and independently associated with treatment outcome.…”

Section: Introductionmentioning

confidence: 99%

Tandem application of flow cytometry and polymerase chain reaction for comprehensive detection of minimal residual disease in childhood acute lymphoblastic leukemia

et al. 1999

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Children with acute lymphoblastic leukemia (ALL) with у0.01% leukemic cells in the bone marrow after remission induction are at a greater risk of relapse. The most promising methods of detecting minimal residual disease (MRD) are flow cytometric identification of leukemia-associated immunophenotypes and polymerase chain reaction (PCR) amplification of antigenreceptor genes. However, neither assay can be applied to all patients. Moreover, both assays carry the risk of false-negative findings due to clonal evolution. The simultaneous use of both assays might resolve these problems, but the correlation between the methods is unknown. We studied serial dilutions of normal and leukemic cells by flow cytometry and PCR amplification of IgH genes and found the two methods highly sensitive (one leukemic cell among 10 4 or more normal cells), accurate (r 2 was 0.999 for flow cytometry and 0.960 for PCR by regression analysis) and concordant (r 2 = 0.962). We then examined 62 bone marrow samples collected from children with ALL in clinical remission. In 12 samples, both techniques detected MRD levels у1 in 10 4 . The percentages of leukemic cells measured by the two methods correlated well (r 2 = 0.978). Of the remaining 50 samples, 48 had MRD levels Ͻ1 in 10 4 . In only two samples results were discordant: 2 in 10 4 and 5 in 10 4 leukemic cells by PCR but Ͻ1 in 10 4 by flow cytometry. We conclude that immunologic and molecular techniques can be used in tandem for universal monitoring of MRD in childhood ALL.

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Importance of the day 7 bone marrow biopsy as a prognostic measure of the outcome in children with acute lymphoblastic leukemia

Cited by 26 publications

References 10 publications

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

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

Substance P – a potent risk factor in childhood lymphoblastic leukaemia

Tandem application of flow cytometry and polymerase chain reaction for comprehensive detection of minimal residual disease in childhood acute lymphoblastic leukemia

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