Abstract
Background aims
The L-index, designed as a quantitative parameter to simultaneously assess the duration
and severity of lymphopenia, and absolute lymphocyte count (ALC) have a prognostic
impact after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However,
discrepancies have been reported in the impact of ALC, and limited information is
currently available on the L-index.
Methods
To search for a better clinical tool, the authors retrospectively compared the simple
L-index at 30 days (sL-index(30)), which aims to make the original L-index more compact,
and ALC at 30 days (ALC(30)) after allo-HSCT in 217 patients who underwent allo-HSCT
at the authors’ institutions.
Results
Median sL-index(30) was 11 712 (range, 4419–18 511) and median ALC(30) was 404 (range,
0–3754). In a multivariate analysis, higher sL-index(30) was associated with a significantly
higher cumulative incidence of relapse (CIR) (hazard ratio [HR], 1.01, 95% confidence
interval [CI], 1.00–1.02, P = 0.02 for every increase of 100 in sL-index(30)) as well as non-relapse mortality
(NRM) (HR, 1.02, 95% CI, 1.00–1.03, P = 0.01 for every increase of 100 in sL-index(30)). Although higher ALC(30) was associated
with significantly lower CIR (HR, 0.94, 95% CI, 0.89–1.00, P = 0.04 for every increase of 100/μL in ALC(30)), it was not extracted as an independent
risk factor for NRM (HR, 0.96, 95% CI, 0.88–1.05, P = 0.39). Higher sL-index(30) was associated with a slightly higher rate of grade
3–4 acute graft-versus-host disease (GVHD) (HR, 1.02, 95% CI, 1.00–1.04, P = 0.12 for every increase of 100 in sL-index(30)) but not chronic GVHD (HR, 1.00,
95% CI, 0.99–1.01, P = 0.63). ALC(30) was not associated with rates of grade 3–4 acute GVHD (HR, 1.02,
95% CI, 0.88–1.17, P = 0.81) or chronic GVHD (HR, 1.02, 95% CI, 0.98–1.06, P = 0.34). In a receiver operating characteristic curve, the cutoff values of sL-index(30)
and ALC(30) for CIR were 9000 and 500, respectively, and the cutoff value of sL-index(30)
for NRM was 12 000.
Conclusions
sL-index(30) is a promising tool that may be applied to various survival outcomes.
A large-scale prospective study is needed to clarify whether medical interventions
based on sL-index(30) values will improve the clinical prognosis of patients.
Key Words
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References
- L-index as a novel index to evaluate both the intensity and duration of lymphopenia after allogeneic hematopoietic stem cell transplantation.Transpl Infect Dis. 2012; 14: 364-373
- Absolute lymphocyte count on day 30 is a surrogate for robust hematopoietic recovery and strongly predicts outcome after T cell-depleted allogeneic stem cell transplantation.Biol Blood Marrow Transplant. 2007; 13: 1216-1223
- Early lymphocyte recovery at 28 d post-transplant is predictive of reduced risk of relapse in patients with acute myeloid leukemia transplanted with peripheral blood stem cell grafts.Eur J Haematol. 2014; 93: 273-280
- Prognostic impact of immune status and hematopoietic recovery before and after fludarabine, IV busulfan, and antithymocyte globulins (FB2 regimen) reduced-intensity conditioning regimen (RIC) allogeneic stem cell transplantation (allo-SCT).Eur J Haematol. 2013; 90: 177-186
- Effect of slow lymphocyte recovery and type of graft-versus-host disease prophylaxis on relapse after allogeneic bone marrow transplantation for acute myelogenous leukemia.Bone Marrow Transplant. 2001; 28: 951-956
- Lymphocyte recovery after allogeneic bone marrow transplantation predicts risk of relapse in acute lymphoblastic leukemia.Leukemia. 2003; 17: 1865-1870
- Absolute lymphocyte count recovery after allogeneic hematopoietic stem cell transplantation predicts clinical outcome.Biol Blood Marrow Transplant. 2015; 21: 873-880
- Early lymphocyte recovery predicts clinical outcome after HSCT with mycophenolate mofetil prophylaxis in the Japanese population.Int J Hematol. 2018; 108: 58-65
- Peripheral blood lymphocyte and monocyte recovery and survival in acute leukemia postmyeloablative allogeneic hematopoietic stem cell transplant.Biol Blood Marrow Transplant. 2012; 18: 600-607
- Lymphocyte reconstitution after allogeneic blood stem cell transplantation for hematologic malignancies.Bone Marrow Transplant. 1998; 21: 33-41
- 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.Transpl Immunol. 2020; 58101262
- Index to predict invasive mold infection in high-risk neutropenic patients based on the area over the neutrophil curve.J Clin Oncol. 2009; 27: 3849-3854
- D-Index-Guided Early Antifungal Therapy Versus Empiric Antifungal Therapy for Persistent Febrile Neutropenia: A Randomized Controlled Noninferiority Trial.J Clin Oncol. 2020; 38: 815-822
- Defining the intensity of conditioning regimens: working definitions.Biol Blood Marrow Transplant. 2009; 15: 1628-1633
- Reduced-intensity conditioning regimen workshop: defining the dose spectrum. Report of a workshop convened by the center for international blood and marrow transplant research.Biol Blood Marrow Transplant. 2009; 15: 367-369
- Validation and refinement of the Disease Risk Index for allogeneic stem cell transplantation.Blood. 2014; 123: 3664-3671
- Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors.Transplantation. 1974; 18: 295-304
- 1994 Consensus Conference on Acute GVHD Grading.Bone Marrow Transplant. 1995; 15: 825-828
- National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report.Biol Blood Marrow Transplant. 2005; 11: 945-956
- National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report.Biol Blood Marrow Transplant. 2015; 21: 389-401
- Analysis of survival by tumor response.J Clin Oncol. 1983; 1: 710-719
- Statistical methods for the analysis and presentation of the results of bone marrow transplants. Part 2: Regression modeling.Bone Marrow Transplant. 2001; 28: 1001-1011
- Investigation of the freely available easy-to-use software 'EZR' for medical statistics.Bone Marrow Transplant. 2013; 48: 452-458
- Factors associated with early molecular remission after T cell-depleted allogeneic stem cell transplantation for chronic myelogenous leukemia.Blood. 2006; 107: 1688-1695
- Increased apoptosis of peripheral blood T cells following allogeneic hematopoietic cell transplantation.Blood. 2000; 95: 3832-3839
- Invasive aspergillosis in allogeneic stem cell transplant recipients: changes in epidemiology and risk factors.Blood. 2002; 100: 4358-4366
- Late cytomegalovirus disease and mortality in recipients of allogeneic hematopoietic stem cell transplants: importance of viral load and T-cell immunity.Blood. 2003; 101: 407-414
- Human herpesvirus 6 infection inhibits specific lymphocyte proliferation responses and is related to lymphocytopenia after allogeneic stem cell transplantation.Bone Marrow Transplant. 1999; 24: 1201-1206
- The incidence, mortality and timing of Pneumocystis jiroveci pneumonia after hematopoietic cell transplantation: a CIBMTR analysis.Bone Marrow Transplant. 2016; 51: 573-580
- Association of the areas over and under the lymphocyte curve with cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation.Transpl Infect Dis. 2021; 23: e13460
Article info
Publication history
Published online: January 03, 2023
Accepted:
November 22,
2022
Received:
August 1,
2022
Publication stage
In Press Corrected ProofIdentification
Copyright
© 2022 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.
