Prospective validation of the L-index reflecting both the intensity and duration of lymphopenia and its detailed evaluation using a lymphocyte subset analysis after allogeneic hematopoietic stem cell transplantation

Kimura, Shun‐ichi; Sato, Miki; Misaki, Yukiko; Yoshimura, Kazuki; Gomyo, Ayumi; Akahoshi, Yu; Harada, Naonori; Tamaki, Masaharu; Kusuda, Machiko; Kameda, Kazuaki; Kawamura, Koji; Terasako‐Saito, Kiriko; Kikuchi, Misato; Tanihara, Aki; Nakasone, Hideki; Kako, Shinichi

doi:10.1016/j.trim.2019.101262

Cited by 5 publications

(11 citation statements)

References 29 publications

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“…This is why ALC values at day 14 and day 21 were well‐correlated with area‐based lymphocyte reconstitution indexes. Lymphocyte reconstitution dynamics in this study were similar to those in previous studies using a lymphocyte subset analysis for detailed evaluation, which showed that ALC, particularly the CD4 + T cell count from day 14, played an important role in protecting against CMV reactivation 9,28 . ALC values at day 14 and day 21 might reflect the recovery of CD4 + T cells.…”

Section: Discussionsupporting

confidence: 85%

“…In our previous studies, the L‐index(30), which is L_AOC during lymphopenia (<700/µL), from the start of the conditioning regimen to day 30 after HSCT was significantly associated with CMV reactivation 8,9 . Although this larger retrospective study confirmed that the L‐index(30) was higher in patients with CMV reactivation with borderline significance, ALC before HSCT did not affect CMV reactivation according to the lymphocyte reconstitution dynamics.…”

Section: Discussionmentioning

confidence: 47%

“…Lymphocyte reconstitution is important for the clinical outcome after allogeneic hematopoietic stem cell transplantation (HSCT), including preventing opportunistic infections such as cytomegalovirus (CMV) infection and attacking residual tumor cells 1‐7 . We previously reported that the L‐index(30), which is the area over the lymphocyte curve (L_AOC) during lymphopenia (<700/µL) from the start of the conditioning regimen to day 30 after HSCT and thus simultaneously reflects both the intensity and duration of lymphopenia, was associated with CMV reactivation 8,9 . Watanabe et al reported that the area under the lymphocyte curve (L_AUC) from day 0 to day 30 after HSCT was useful for predicting CMV reactivation in allogeneic HSCT recipients 10 .…”

Section: Introductionmentioning

confidence: 99%

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Association of the areas over and under the lymphocyte curve with cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation

Kimura

Nakamura

Kawamura

et al. 2020

Transplant Infectious Dis

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Background We retrospectively compared the impact of the areas over and under the lymphocyte curve (L_AOC vs L_AUC) on cytomegalovirus (CMV) reactivation after allogeneic hematopoietic stem cell transplantation (HSCT). Methods Among 394 consecutive patients who underwent their first allogeneic HSCT at our center between 2007 and 2018, 301 patients met the inclusion criteria. L_AOC was calculated as the area over the lymphocyte curve during lymphopenia (absolute lymphocyte count [ALC] <700/μL). We calculated L_AOC and L_AUC from day 0 to day 15 (L_AOC15, L_AUC15) and from day 0 to day 30 (L_AOC30, L_AUC30). Results CMV antigenemia was defined as more than 3 cells/2 slides by the C10/11 method and detected in 204 cases (CMV reactivation) at a median of 39 days after HSCT. Although there were significant differences in L_AOC15, L_AOC30, L_AUC15, and L_AUC30 between patients with and without CMV reactivation, there was no difference in accuracy for predicting CMV reactivation between L_AOC and L_AUC. In a multivariate analysis, L_AOC15 and L_AUC15 were each identified as independent predictive factors for CMV reactivation, along with advanced age and CMV serostatus. However, ALC at day 14 or day 21 was as accurate as area‐based indexes such as L_AOC15 and L_AUC15. L_AOC15 and L_AUC15 were significantly associated with longer duration of anti‐CMV antiviral therapy while ALC was not. Conclusions L_AOC15 and L_AUC15 had similar impacts on CMV reactivation. Although these area‐based indexes were not superior to ALC for predicting CMV reactivation, they might predict patients who need longer duration of antiviral therapy more accurately.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 47%

Section: Introductionmentioning

confidence: 99%

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Association of the areas over and under the lymphocyte curve with cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation

Kimura

Nakamura

Kawamura

et al. 2020

Transplant Infectious Dis

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“…It has been reported that calculation of the area over or under the curve regarding the severity of cytopenia or exposure to viremia was useful for accurately evaluating the clinical impact 4,32,33 . In this study, the D‐index and c‐D‐index were each more accurate than the duration of neutropenia and as accurate as the duration of profound neutropenia for predicting IFD.…”

Section: Discussionmentioning

confidence: 66%

“…It has been reported that calculation of the area over or under the curve regarding the severity of cytopenia or exposure to viremia was useful for accurately evaluating the clinical impact. 4,32,33 In This study has some limitations. First, this was a retrospective study from a single institute.…”

Section: Discussionmentioning

confidence: 92%

Impact of neutropenia evaluated in terms of the D‐index on invasive fungal disease while on empiric or preemptive antifungal treatment strategy in the early phase after allogeneic hematopoietic stem cell transplantation

Kimura

Nakamura

Kawamura

et al. 2020

Transplant Infectious Dis

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Background: We retrospectively evaluated the association between the D-index, which reflects both the depth and duration of neutropenia, and proven/probable invasive fungal disease (IFD) early after allogeneic hematopoietic stem cell transplantation (HSCT) at our center (n = 394). Methods: The D-index was defined as the area over the neutrophil curve during neutropenia. The cumulative D-index from the start of neutropenia until the development of infection (c-D-index) was also evaluated as a real-time assessment of neutropenia. Results: There were 19 cases of early proven/probable IFD before and within 1 week after engraftment. Fifteen cases (78.9%) were seen as breakthrough infection while on empiric (n = 7), preemptive (n = 4) or prophylactic (n = 4) antifungal administration with mold-active agents. The c-D-index and lower performance status were identified as independent significant predictive factors for IFD. A receiver operating characteristic (ROC) curve analysis showed that the D-index and c-D-index were more accurate than the simple duration of neutropenia and as accurate as the duration of profound neutropenia for predicting IFD. The sensitivity, specificity, and positive and negative predictive values of the c-D-index using an appropriate cutoff (CO) value (10 644) determined by ROC curve analysis were 73.1%, 63.2%, 9.1%, and 97.9%, respectively. The advantage of the c-D-index to cumulative days of neutropenia in terms of positive and negative predictive values seemed to be small. Conclusions: The appropriate CO value for the c-D-index for predicting IFD was as high as 10 644 in allogeneic HSCT with a more frequent use of empiric antifungal therapy. The c-D-index is useful for assessing the risk of breakthrough IFD.

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Prognostic impact of the simple L-index and absolute lymphocyte count early after allogeneic hematopoietic stem cell transplantation

et al. 2023

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Prospective validation of the L-index reflecting both the intensity and duration of lymphopenia and its detailed evaluation using a lymphocyte subset analysis after allogeneic hematopoietic stem cell transplantation

Cited by 5 publications

References 29 publications

Association of the areas over and under the lymphocyte curve with cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation

Association of the areas over and under the lymphocyte curve with cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation

Impact of neutropenia evaluated in terms of the D‐index on invasive fungal disease while on empiric or preemptive antifungal treatment strategy in the early phase after allogeneic hematopoietic stem cell transplantation

Prognostic impact of the simple L-index and absolute lymphocyte count early after allogeneic hematopoietic stem cell transplantation

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