Time-Series Reconstruction of CBC Profile of Pediatric Cancer Patients for Two Years after Hematopoietic Stem Cell Transplantation Using Language Programming

In this single center and retrospective study, we analyzed every single patient totaling 249 patients who was admitted and undergone hematopoietic stem cell transplantation (HSCT) at our institution from year 2013 to 2019. Twenty three patients were excluded mainly due to returning home country after HSCT without further follow up at our institution. We re-analyzed the remaining 226 patients (169 alive patients and 57 expired patients) and re-constructed time-series laboratory data of white blood cell (WBC) count (Figure 1), hemoglobin, platelet, absolute neutrophil count (ANC), monocytes number, blood urea nitrogen, creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, lactate dehydrogenase (LDH), cyclosporine level, and/or tacrolimus level for up to two years since their last HSCT. These large sets of data were visualized by custom-written codes using language programming. We performed subgroup analysis of these patients' laboratory data according to the tumor type, which was grouped into acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), other types of leukemia not aforementioned, lymphoma, solid tumor, aplastic anemia and other diseases including neurologic disease or immunodeficiency. We also compared these patients' laboratory data according to immunosuppressant used (cyclosporine versus tacrolimus), and hematopoietic stem cell transplantation procedures employed (allogeneic peripheral blood stem cell transplantation (PBSCT), autologous PBSCT or bone-marrow transplantation).

In all patients analyzed who remain alive after HSCT (male 100 patients (59%), female 69 patients (41%), the median WBC engraftment time was 13 days with interquartile range (IQR) of 11-15 days). Both WBC and ANC steadily increased after engraftment up to 400 days since HSCT and reached plateau level at 7,000cells/uL for WBC and 3,000cells/uL for ANC. Hemoglobin and platelet showed faster recovery time since HSCT as hemoglobin level of 12 g/dL and platelet count of 200x10^9/L both reached at 300 days since HSCT. Patients underwent HSCT due to the occurrence of solid tumor generally showed shorter WBC engraftment time of 11 days with IQR of 10-12 days while those with hematologic malignancy showed relatively longer WBC engraftment time of 14 days with IQR of 12-16 days. In subgroup analysis of hematologic malignancy categorized into ALL, AML, other leukemia not aforementioned and lymphoma, no significant differences in engraftment time or general trend over two-year time-course of WBC, ANC, hemoglobin and platelet. In sharp contrast, 57 patients who have expired since HSCT showed WBC recovery after engraftment - the median WBC engraftment time was 13 days with IQR of 11-16 days - up to 3,000cells/uL but the WBC count did not increase thereafter in the following two years. The hemoglobin and platelet plateau for these expired patients were markedly lower than those alive as hemoglobin level was maintained around 9 g/dL (Figure 2) and platelet count ranged from 50 to 90x10^9/L since HSCT.

HSCT is not the end but the beginning of return to normal daily activities for many patients and vigilant long-term care of these patients is crucial not only for the patients but also for their families. As analogous to Fenton growth chart being used for premature babies and their parents to visually aid their growth progression at outpatient clinic, we aimed at constructing time-series laboratory data of HSCT patients since transplantation to serve as reference curves for HSCT patients at our institution with hope that these reference curves as a visual aid may better assist and assure those patients and their families with successful recovery and for those without successful course, early intervention and further treatment may be better understood and accepted by the patients and their families.

Figure 1. Time course of white blood cell count for each patient after HSCT. Each line is color-coded differently and represents a single patient. Red curve is the median of all patients with error bars denoting interquartile range. Shaded area also represents interquartile range.

Figure 2. Time course of hemoglobin trend for two years after HSCT. Median average of 169 alive patients' data (red) was compared with that of 57 expired patients (blue). Error bars represent interquartile ranges.

No relevant conflicts of interest to declare.