SUPPLEMENTAL TABLE II. Literature of ALC During Induction Therapy of ALL

Reference / Nr. of pts. / Therapy protocol / Age at Dx (median, range) / Specific features of patient group / Analysed variables / Survival within entire cohort / ALC- cutoff values with prognostic significance for survival / Survival in patient groups divided by ALC cutoff values (lower ALC vs. higher ALC) / Hazard Ratio (95% CI) / Survival in Cox multivariate analysis / Other measeurments
De Angulo et al. (2007)[1] / 89 / CCG-1952/CCG-1961, CCG-1991,
hyper-CVAD / 11 (0.25-21) / 55% (n=49) of patients age 10-21y at Dx / ALC-15, ALC-21, ALC-28
ANC-15, ANC-21, ANC-28
PLT-15,
PLT-21,
PLT-28 / 6y OS 72%
6y RFS 64% / ALC-15 <350 cells/µL for 6y OS and RFS
ALC-21 <350 cells/µL for 6y RFS
ALC-28 <350 cells/µL for 5y RFS
ALC
<350 cells/µL
at all time points
for 5y RFS / OS 55% vs. 87% (p=0.018)
RFS 43% vs. 80% (p=0.002)
RFS 47% vs. 80%
(p=0.03)
RFS 57% vs. 76% (p=0.03)
RFS 51% vs. 89% (p=0.018) / 4.1 (1.3–13)
4.5 (1.7–12)
2.9 (1.1–7.5)
3.3 (1.1–9.5)
6 (1.4–26) / ALC-15
associated with 6y RFS after adjusting for
age, initial WBC, treatment regimen, BM blast %
on d7, unfavorable cytogenetics
(HR 5.2; p=0.008) / ALC-15 <350 cells/µL
had a 6-year RFR of
47% vs. 82%
(HR 4.8, p=0.003)
Differences in OS according ALC cutoff 350 cells/µL on d21 and 28 were not significant
ANC and PLT values were not prognostic for survival
Martínez et al. (2011) [2] / 105 / nr / 5 (1-17) / ALC-15, ALC-28 / 5y OS 85%
5y EFS 84% / ALC-15 <1000 cells/µL for 6y OS and RFS
ALC-28 <1000 cells/µL for 6y OS and RFS / OS 59% vs. 89% (p=0.001)
RFS 51% vs. 83%
(p=0.002)
OS 66% vs. 86% (p=0.01)
RFS 55% vs. 82% (p=0.04) / 8.89
(1.64-11.00) p=0.003
7.95
(1.46–8.40)
p=0.005
5.27
(1.17-1.17) p=0.022
3.743
(0.98-5.61) p=0.049 / ALC-15
associated with 5y OS and RFS after adjusting forinitial WBC, response to treatment (absolute blast count on d8, BM blast %
at d15 and d33), unfavorable cytogenetics
(OS 10.60 (1.94-14.58) p=0.001
RFS 7.5 (1.4-8.7) p=0.006
Rabin et al. (2012) [3] / 171 / COG P9904-P9906 / 5.4 (1-17) / 1-21y o pts; BCP-ALL / ALC-1,
ALC-15, ALC-22, ALC-29
ANC-1,
ANC-15, ANC-22, ANC-29
PLT-1,
PLT-15,
PLT-22,
PLT-29 / nr / ALC-29 <1500 cells/µL for 6y OS and RFS / OS 74% vs. 96% (p=0.001)
EFS 62% vs 80% (p=0.018) / 7.0 (2.2-22.3)
2.2 (1.1-4.2) / ALC-29 remains prognostic for OS (but not for RFS) after adjusting for age at Dx, initial WBC and cytogenetics / ALC-29 <1500 cutoff helps redefine risk stratification in combination with MRD-29 results; with use of the two markers 4 patient groups can be determined with statistically significant differences in OS and EFS
PLT-29 <100.000 is associated with dismal OS (65% vs. 95%; 9.1 (3.1-26.3; p<0.001) and RFS (65% vs. 80%; 2.4 (0.99-5.70; p=0.053) in univariate but not in multivariate analysis
Alkayed et al. (2012) [4] / 136 / St.Jude Total XIII and XV / nr (1-18) / 7-drug induction, arabic ethnicity / ALC-0, ALC-15, ALC-36 / no significance / no significance / ALC-0/15/36 <1500 cutoff values were not prognostic for OS and EFS
Sun et al. (2012) [5] / 198 / various / 38 (18-64) / Adult pts / ALC-28 / median OS 29.5 months and median EFS 24.9 months / ALC-28 <350 cells/µL / median OS 17.6 m vs. 47.4 m (p=0.007)
median EFS 13.9m vs. 42.1m (p=0.006) / 1.98
2.08 / ALC-28 remains prognostic for lenght of OS and EFS after adjusting for initial WBC and cytogenetics
Shen et al. (2013) [6] / 140 / NPCAC97 / 4.1 (1.1-14.3) / BCP-ALL / ALC-0,
ALC-8,
ALC-22 / nr / nr / nr / nr / nr / ALC-22 correlates with level of MRD-22 in Spearman's rank correlation
ALC-22/ALC-8 ratio correlates with level of MRD-22
ALC-0 correlates with level of MRD-22 in the CD45neg group
Rubnitz et al. (2013) [7] / St. Jude Total XV / nr / ALC-43 / 5y OS93.5%
5y EFS85.6% / ALC-43 <500 cells/µLa / OS 82.4% vs. 95% (p=0.023) / 2.82
(1.15-6.91) / no significance / EFS not significant
ALC-43 >500 cells/µL is associated with negative MRD-43 results, B-ALL and lower risk in stratification;
higher ALC-43 results tested as a continuous variable are associated with younger age (1-9), B-ALL and low risk ALL;
pts with lower ALC-43 results tend to have lower PLT-43 and WBC-43 as well
ALC-43 as a continuous variable is associated with OS, but not with EFS
ALC-43 >500 cells is associated with OS in the MRD-43 negative group
Hatzipantelis et al. (2007) [8] / 117 / BFM ALLIC 2009 / 5.8 (0.6-17) / ALC-29 / 5y OS 90.6%,
5y EFS 88.9% / ALC-29 <350 cells/µL / OS 69.2% vs. 92.3% (p=0.05) / 2.2
Cheng et al (2014) [9] / 119 / NPCAC97 / 4.4 (1.1-14.3) / B-ALL / ALC-0,
ALC-22, ALC-36
ALC-22/ALC-0 ratio / 5y OS 89.9%,
5y EFS 79.8% / ALC-0 <15700 cells µL
ALC-22 <900 cells/µL / OS nr
EFS nr
OS 80% vs. 94.9% (p=0.027) / 6.01
(3.01-13.33)
p=0.0022
3.31 (1.51-7.7)
p=0.0131
3.63
(1.06-12.42) p=0.0396 / ALC-22: no significance / ALC-22/ALC-0 <10% associated with OS (72.9% vs. 95.6%, p<0.05) and EFS (62.2% vs. 87.8%, p=0.0026);
ALC-22/ALC-0 <10% remains significant in uni- and multivariate anlyses
ALC-22 with <900 cells/µL cutoff: not significant for EFS
Gupta et al. (2015) [10] / 212 / BFM / 6 (1-18) / ALC-15, ALC-29 / 5y OS 81.4%,
5y EFS 72.1%
5y RFS 75.6% / ALC-15 <500 cells/µL
ALC-29 <1000 cells/µL / OS 54.4% vs. 84.1% (p<0.001)
EFS 34.8% vs. 72.3%
(p<0.001)
RFS 41.3% vs. 79.2%
(p<0.001)
OS 47.8% vs. 88.1% (p<0.001)
EFS 32.6% vs. 77.8%
(p<0.001)
RFS 35.2% vs. 86.6%
(p<0.001) / 2.0 (1.1-3.7)
2.5 (1.5-4.2)
3.43 (1.8-6.4)
2.3 (1.3-4.1)
2.2 (1.3-3.7)
2.54 (1.4-4.7) / ALC-15, ALC-29 and PLT-29 (106 cells/µL) remain prognostic in multivariate analysis / Lower ALC-15 and ALC-29 werewere also associated
with lower ANC and PLC on
these days
ALC-15 <500 cells/µL was significantly associated with older age (10 y and older), HR group and nervous system disease
ALC-29 <1000 cells/µL was significantly associated with
older age (10 y and older) and HR group
PLT-29 <106 cells/µL is associated with worse OS, EFS and RFS

Abbrevations:

a)Dx indicates diagnosis, b) ALC Absolute Lymphocyte Count, c) y Years, d) ANC Absolute Neutrophil Count, e) PLT Platelet Count,
f) OS Overall Survival, g) RFS Relapse Free Survival, h) BM Bone Marrow, i) d Day, j) RFR Relapse Free Rate, k) EFS event Free Survival, l) nr Not Reported, m) pts Patients, n) m Months, o) HR Hazard Ratio, p) MRD Minimal Residual Disease

Reference List:

  1. De Angulo G, Yuen C, Palla SL, Anderson PM, Zweidler-McKay PA. Absolute lymphocyte count is a novel prognostic indicator in ALL and AML: implications for risk stratification and future studies. Cancer 2008:112:407-415.
  2. Anoceto Martínez A, González Otero A, Guerchicoff de Svarch E, Arencibia Nuñez A, Jaime JC, Dorticos E, Sarduy S, González L. [Absolute lymphocyte count as a prognostic factor in children with acute lymphoblastic leukemia]. Anales de pediatria (Barcelona, Spain : 2003) 2012:2011/08/25:10.
  3. Rabin KR, Gramatges MM, Borowitz MJ, Palla SL, Shi X, Margolin JF, Zweidler-McKay PA. Absolute lymphocyte counts refine minimal residual disease-based risk stratification in childhood acute lymphoblastic leukemia. Pediatric blood & cancer 2012:2011/11/22:468-474.
  4. Alkayed K, Halalsheh H, Khattab E, Abualruz AR, Ibrahim A, Madanat F.Lack of prognostic significance of absolute lymphocyte count after intensive induction therapy in childhood acute lymphoblastic leukemia.Pediatr Blood Cancer. 2012 Aug;59(2):351. doi: 10.1002/pbc.24120. Epub 2012 Feb 29.
  5. Sun D, Elson P, Liedtke M, Medeiros BC, Earl M, Alizadeh A, Bates J, Sekeres MA, Coutre S, Kalaycio M, Sobecks R, Copelan E, Advani AS. Absolute lymphocyte count at day 28 independently predicts event-free and overall survival in adults with newly diagnosed acute lymphoblastic leukemia. American journal of hematology 2012:2012/06/26:957-960.
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  8. Hatzipantelis E, Pana ZD, Vlachou M, Papageorgiou T, Tragiannidis A, Athanassiadou F. Peripheral blood lymphocyte recovery and overall survival in pediatric acute lymphoblastic leukemia. Pediatric blood & cancer 2014:2013/09/17:181-183.
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  10. Gupta A, Kapoor G, Jain S, Bajpai R. Absolute Lymphocyte Count Recovery Independently Predicts Outcome in Childhood Acute Lymphoblastic Leukemia: Experience From a Tertiary Care Cancer Center of a Developing Country. Journal of pediatric hematology/oncology 2015:2015/07/23:e143-e149.