Pushpam Deepam, Rajput Nishi, Chopra Anita, Vishnubhatla Sreenivas, Kumari Mamta, Kumar Rajive, Bakhshi Sameer
a Department of Medical Oncology , Dr. B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences , New Delhi , India.
b Department of Laboratory Oncology , Dr. B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences , New Delhi , India.
Pediatr Hematol Oncol. 2019 Apr;36(3):138-150. doi: 10.1080/08880018.2019.1594469. Epub 2019 May 3.
Absolute lymphocyte count (ALC) has been associated with overall survival (OS) and event-free survival, but we do not know if ALC is associated with minimal residual disease (MRD) at the end of induction (EOI) and whether it can be used as surrogate marker in resource limited settings. Immunological differences between MRD-positive and MRD-negative B ALL patients at the EOI are not known at present. This prospective study evaluated the association of ALC and peripheral blood lymphocyte subset percentage at the EOI with MRD. ALC was done at baseline, day 8, and day 15 and at EOI. Assessment for MRD and peripheral blood lymphocyte subset was done at EOI. In 2-year study duration, 197 B cell acute lymphoblastic leukemia (ALL) patients were recruited out of which 150 were analyzed. Peripheral lymphocyte subset percentage was available for 58 patients. We found that ALC at baseline, day 8, day 15, and EOI was not associated with MRD. Day 8 ALC was significantly higher in poor steroid responders (day 8 blasts > 1 × 10 cells/l) ( < 0.0001). At the EOI, CD4CD8 cell percentage in peripheral blood were significantly higher in MRD-positive patients than MRD-negative patients ( = 0.01). Our study suggests that ALC at any point is not a surrogate marker for MRD. Immunologically MRD-positive and MRD-negative patients differ in CD4CD8 cells. The role of CD8T and TCRαβCD3T cells in eliminating residual leukemic cells need to be studied further by functional assays.
绝对淋巴细胞计数（ALC）与总生存期（OS）和无事件生存期相关，但我们不知道ALC是否与诱导结束时的微小残留病（MRD）相关，以及它是否可在资源有限的情况下用作替代标志物。目前尚不清楚诱导结束时MRD阳性和MRD阴性的B淋巴细胞白血病（B-ALL）患者之间的免疫学差异。这项前瞻性研究评估了诱导结束时ALC和外周血淋巴细胞亚群百分比与MRD的相关性。在基线、第8天、第15天和诱导结束时进行ALC检测。在诱导结束时进行MRD和外周血淋巴细胞亚群评估。在为期2年的研究期间，招募了197例B细胞急性淋巴细胞白血病（ALL）患者，其中150例进行了分析。58例患者可获得外周淋巴细胞亚群百分比数据。我们发现基线、第8天、第15天和诱导结束时的ALC与MRD无关。在激素反应不佳的患者中（第8天原始细胞>1×10⁹细胞/升），第8天的ALC显著更高（P<0.0001）。在诱导结束时，MRD阳性患者外周血中的CD4⁺CD8⁻细胞百分比显著高于MRD阴性患者（P=0.01）。我们的研究表明，任何时间点的ALC都不是MRD的替代标志物。在免疫学上，MRD阳性和MRD阴性患者在CD4⁺CD8⁻细胞方面存在差异。需要通过功能试验进一步研究CD8⁺T细胞和TCRαβ⁺CD3⁺T细胞在清除残留白血病细胞中的作用。
