Limits...
Prediction of outcomes by early treatment responses in childhood T-cell acute lymphoblastic leukemia: a retrospective study in China.

Wei W, Chen X, Zou Y, Chang L, An W, Wan Y, Liu T, Yang W, Chen Y, Guo Y, Zhu X - BMC Pediatr (2015)

Bottom Line: Prednisone poor responder was strongly associated with increased chance of induction failure (14.8%) and decreased survival rate (5 year EFS rate, 51.1 % (SE, 10.5)).MRD ≥ 10(-2) at TP1 or MRD ≥ 10(-3) at TP2 was significantly related to dismal prognosis.Risk groups classified by MRD at two time points could stratify patients into different groups: 29.0% of the patients were MRD standard risk (MRD < 10(-4) at both time points) with 3-year EFS rate of 100%, 29.0% were MRD high risk (MRD ≥ 10(-2) at TP1 or MRD ≥ 10(-2) at TP2) with 3-year EFS rate of 55.6% (SE, 16.6) , and the rest of patients were defined as MRD intermediate risk with 3-year EFS rate of 85.7% (SE, 13.2).

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin, 300020, Peoples Republic of China. weiwei2013pumc@gmail.com.

ABSTRACT

Background: Early treatment responses are important prognostic factors in childhood T-cell acute lymphoblastic leukemia (T-ALL) patients. The predictive values of early treatment responses in Chinese childhood T-ALL patients were still unknown.

Methods: From January 2003 to December 2012, 74 consecutive patients aged ≤ 15 years with newly diagnosed T-ALL were treated with BCH-2003 protocol or CCLG-2008 protocol in the Department of Pediatric, Institute of Hematology and Blood Diseases Hospital in China. Predictive values of early treatment responses, including prednisone response, bone marrow morphology at day 15 and day 33 during induction chemotherapy, and minimal residual disease (MRD) monitored by flow cytometry after induction therapy (time point 1, TP1) and before consolidation therapy (time point 2, TP2), were analyzed.

Results: The 5-year event free survival (EFS) and overall survival (OS) rates for these patients were 62.5% (SE, 6.4) and 62.7% (SE, 6.6), respectively. Prednisone poor responder was strongly associated with increased chance of induction failure (14.8%) and decreased survival rate (5 year EFS rate, 51.1 % (SE, 10.5)). Patients with ≥ 25% blast cells in bone marrow at day 15 were more likely to have an inferior outcome. 93.2% of the T-ALL patients achieved complete remission at day 33 while patients with resistant disease all died of disease progression. MRD ≥ 10(-2) at TP1 or MRD ≥ 10(-3) at TP2 was significantly related to dismal prognosis. Risk groups classified by MRD at two time points could stratify patients into different groups: 29.0% of the patients were MRD standard risk (MRD < 10(-4) at both time points) with 3-year EFS rate of 100%, 29.0% were MRD high risk (MRD ≥ 10(-2) at TP1 or MRD ≥ 10(-2) at TP2) with 3-year EFS rate of 55.6% (SE, 16.6) , and the rest of patients were defined as MRD intermediate risk with 3-year EFS rate of 85.7% (SE, 13.2).

Conclusion: Our study demonstrated that MRD was the most powerful predictor of treatment outcome in childhood T-ALL patients and conventional morphological assessments of treatment response still played important roles in predicting treatment outcome and tailoring treatment intensity especially in countries with inadequate skills or financial resources for MRD monitoring.

No MeSH data available.


Related in: MedlinePlus

Kaplan-Meier estimate of event-free survival according to bone marrow morphology at day 15 during induction chemotherapy in 65 T-ALL patients. a Patients classified into three groups: M1 (bone marrow blast <5 %), M2 (bone marrow blast 5 % and <25 %), and M3 (bone marrow blast ≥25 %). b Patients classified into two groups: M1 + M2 (bone marrow blast <25 %) and M3 (bone marrow blast ≥25 %). SE, standard error
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4502910&req=5

Fig3: Kaplan-Meier estimate of event-free survival according to bone marrow morphology at day 15 during induction chemotherapy in 65 T-ALL patients. a Patients classified into three groups: M1 (bone marrow blast <5 %), M2 (bone marrow blast 5 % and <25 %), and M3 (bone marrow blast ≥25 %). b Patients classified into two groups: M1 + M2 (bone marrow blast <25 %) and M3 (bone marrow blast ≥25 %). SE, standard error

Mentions: Bone marrow smears at day 15 of induction therapy were eligible for evaluation in 65 patients. 36 (55.4 %) patients were defined as M1 status, 19 (29.2 %) patients were classified as M2 status and 10 (15.4 %) patients were defined as M3 status. The 5-year EFS rates were 61.2 % (SE, 9.2), 73.7 % (SE, 13.7) and 50.0 % (SE, 15.8) for the patients with M1, M2 and M3 status, respectively (P = 0.129, Fig. 3a). M3 status at day 15 is internationally recognized as a poor prognostic factor and there was no difference in treatment outcome between M1 and M2 patients in our study. Thus, we combined M1 and M2 patients into one group to compare with M3 patients. The 5-year EFS rate for M3 patients was lower than that for M1/2 patients with borderline significance (50 % (SE, 15.8) VS 65.3 % (SE, 7.7), P = 0.073, Fig. 3b). The relationships between clinical features and BM status at day 15 were also analyzed and no significant correlation was found (Additional file 1: Table S6).Fig. 3


Prediction of outcomes by early treatment responses in childhood T-cell acute lymphoblastic leukemia: a retrospective study in China.

Wei W, Chen X, Zou Y, Chang L, An W, Wan Y, Liu T, Yang W, Chen Y, Guo Y, Zhu X - BMC Pediatr (2015)

Kaplan-Meier estimate of event-free survival according to bone marrow morphology at day 15 during induction chemotherapy in 65 T-ALL patients. a Patients classified into three groups: M1 (bone marrow blast <5 %), M2 (bone marrow blast 5 % and <25 %), and M3 (bone marrow blast ≥25 %). b Patients classified into two groups: M1 + M2 (bone marrow blast <25 %) and M3 (bone marrow blast ≥25 %). SE, standard error
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4502910&req=5

Fig3: Kaplan-Meier estimate of event-free survival according to bone marrow morphology at day 15 during induction chemotherapy in 65 T-ALL patients. a Patients classified into three groups: M1 (bone marrow blast <5 %), M2 (bone marrow blast 5 % and <25 %), and M3 (bone marrow blast ≥25 %). b Patients classified into two groups: M1 + M2 (bone marrow blast <25 %) and M3 (bone marrow blast ≥25 %). SE, standard error
Mentions: Bone marrow smears at day 15 of induction therapy were eligible for evaluation in 65 patients. 36 (55.4 %) patients were defined as M1 status, 19 (29.2 %) patients were classified as M2 status and 10 (15.4 %) patients were defined as M3 status. The 5-year EFS rates were 61.2 % (SE, 9.2), 73.7 % (SE, 13.7) and 50.0 % (SE, 15.8) for the patients with M1, M2 and M3 status, respectively (P = 0.129, Fig. 3a). M3 status at day 15 is internationally recognized as a poor prognostic factor and there was no difference in treatment outcome between M1 and M2 patients in our study. Thus, we combined M1 and M2 patients into one group to compare with M3 patients. The 5-year EFS rate for M3 patients was lower than that for M1/2 patients with borderline significance (50 % (SE, 15.8) VS 65.3 % (SE, 7.7), P = 0.073, Fig. 3b). The relationships between clinical features and BM status at day 15 were also analyzed and no significant correlation was found (Additional file 1: Table S6).Fig. 3

Bottom Line: Prednisone poor responder was strongly associated with increased chance of induction failure (14.8%) and decreased survival rate (5 year EFS rate, 51.1 % (SE, 10.5)).MRD ≥ 10(-2) at TP1 or MRD ≥ 10(-3) at TP2 was significantly related to dismal prognosis.Risk groups classified by MRD at two time points could stratify patients into different groups: 29.0% of the patients were MRD standard risk (MRD < 10(-4) at both time points) with 3-year EFS rate of 100%, 29.0% were MRD high risk (MRD ≥ 10(-2) at TP1 or MRD ≥ 10(-2) at TP2) with 3-year EFS rate of 55.6% (SE, 16.6) , and the rest of patients were defined as MRD intermediate risk with 3-year EFS rate of 85.7% (SE, 13.2).

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin, 300020, Peoples Republic of China. weiwei2013pumc@gmail.com.

ABSTRACT

Background: Early treatment responses are important prognostic factors in childhood T-cell acute lymphoblastic leukemia (T-ALL) patients. The predictive values of early treatment responses in Chinese childhood T-ALL patients were still unknown.

Methods: From January 2003 to December 2012, 74 consecutive patients aged ≤ 15 years with newly diagnosed T-ALL were treated with BCH-2003 protocol or CCLG-2008 protocol in the Department of Pediatric, Institute of Hematology and Blood Diseases Hospital in China. Predictive values of early treatment responses, including prednisone response, bone marrow morphology at day 15 and day 33 during induction chemotherapy, and minimal residual disease (MRD) monitored by flow cytometry after induction therapy (time point 1, TP1) and before consolidation therapy (time point 2, TP2), were analyzed.

Results: The 5-year event free survival (EFS) and overall survival (OS) rates for these patients were 62.5% (SE, 6.4) and 62.7% (SE, 6.6), respectively. Prednisone poor responder was strongly associated with increased chance of induction failure (14.8%) and decreased survival rate (5 year EFS rate, 51.1 % (SE, 10.5)). Patients with ≥ 25% blast cells in bone marrow at day 15 were more likely to have an inferior outcome. 93.2% of the T-ALL patients achieved complete remission at day 33 while patients with resistant disease all died of disease progression. MRD ≥ 10(-2) at TP1 or MRD ≥ 10(-3) at TP2 was significantly related to dismal prognosis. Risk groups classified by MRD at two time points could stratify patients into different groups: 29.0% of the patients were MRD standard risk (MRD < 10(-4) at both time points) with 3-year EFS rate of 100%, 29.0% were MRD high risk (MRD ≥ 10(-2) at TP1 or MRD ≥ 10(-2) at TP2) with 3-year EFS rate of 55.6% (SE, 16.6) , and the rest of patients were defined as MRD intermediate risk with 3-year EFS rate of 85.7% (SE, 13.2).

Conclusion: Our study demonstrated that MRD was the most powerful predictor of treatment outcome in childhood T-ALL patients and conventional morphological assessments of treatment response still played important roles in predicting treatment outcome and tailoring treatment intensity especially in countries with inadequate skills or financial resources for MRD monitoring.

No MeSH data available.


Related in: MedlinePlus