Severe, persistent, and fatal T‐cell immunodeficiency following therapy for infantile leukemia

Geerlinks, Ashley V.; Issekutz, Thomas B.; Wahlstrom, Justin T.; Sullivan, Kathleen E.; Cowan, Morton J.; Dvorak, Christopher C.; Fernandez, Conrad V.

doi:10.1002/pbc.26108

Cited by 12 publications

(12 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Fifteen completed the chemotherapy, and 3 discontinued postinduction protocol therapy because of an adverse event (n 5 1), guardian's choice (n 5 1), or protocol violation (n 5 1). Notably, the IR patient who discontinued because of an asparaginase-induced allergic event developed severe cytomegalovirus infection as a result of secondary T-cell immunodeficiency after chemotherapy completion, similar to the reported case series by Geerlinks et al 17 This patient eventually died of infection, although immune reconstitution by HSCT was attempted. In summary, treatment failure observed among the 19 IR patients was 1 death in CR.…”

Section: Outcomes Of Infants With Kmt2a-r Allsupporting

confidence: 80%

A risk-stratified therapy for infants with acute lymphoblastic leukemia: a report from the JPLSG MLL-10 trial

Tomizawa

Miyamura

Imamura

et al. 2020

Blood

103

View full text Add to dashboard Cite

The prognosis of infants with acute lymphoblastic leukemia (ALL), particularly those with KMT2A gene rearrangement (KMT2A-r), is dismal. Continuous efforts have been made in Japan to investigate the role of stem cell transplantation (HSCT) for infants with KMT2A-r ALL, but improvement in outcomes was modest. In the Japanese Pediatric Leukemia/Lymphoma Study Group trial MLL-10 (registered at umin.ac.jp as UMIN000004801), infants with ALL were stratified into three risk groups (low-risk, LR; intermediate-risk, IR; high-risk, HR) according to KMT2A status, age, and presence of central nervous system leukemia. A modified Children's Oncology Group AALL0631 chemotherapy with addition of high-dose cytarabine in early intensification was introduced to KMT2A-r patients, and the option of HSCT was restricted to HR patients. The role of minimal residual disease (MRD) was also evaluated. Ninety eligible infants were stratified into LR (N=15), IR (N=19), or HR (N=56). The 3-year event-free survival (EFS) rate (standard error) for patients with KMT2A-r ALL (IR+HR) was 66.2% (5.6%) and 93.3% (6.4%) for those with KMT2A-g ALL (LR). The 3-year EFS rate was 94.4% (5.4%) for IR and 56.6% (6.8%) for HR patients. In multivariable analysis, female sex and MRD ≧0.01% at end of early consolidation were significant poor prognostic factors. Risk stratification and introduction of intensive chemotherapy in the current study were effective and able to eliminate HSCT for a subset of infants with KMT2A-r ALL. Early clearance of MRD seems to have translated into favorable outcomes and should be incorporated into risk stratifications in future trials.

show abstract

Section: Outcomes Of Infants With Kmt2a-r Allsupporting

confidence: 80%

A risk-stratified therapy for infants with acute lymphoblastic leukemia: a report from the JPLSG MLL-10 trial

Tomizawa

Miyamura

Imamura

et al. 2020

Blood

103

View full text Add to dashboard Cite

show abstract

“…Yet, frequently reported late complications of HSCT recipients in infancy include growth retardation or failure, obesity, gonadal dysfunction, hypothyroidism, and neurocognitive deficits. T‐cell immunodeficiency has also been reported 32 33,34 …”

Section: Discussionmentioning

confidence: 99%

Allogeneic hematopoietic stem cell transplantation in infants is associated with significant morbidity and mortality

Oikonomopoulou

Paisiou

Ioannidou

et al. 2022

Pediatric Transplantation

View full text Add to dashboard Cite

Background: Infants are subjected to hematopoietic stem cell transplantation (HSCT) due to malignant and non-malignant diseases. However, specific data concerning the outcome and transplantation-related complications in infants, as a separate age group, are limited. Our aim was to evaluate the impact of infancy on the outcome, toxicity, and complications after HSCT. Methods:We retrospectively analyzed data of 55 infants that underwent HSCT in our unit from May 1997 until February 2020, emphasizing on the probability of overall survival (OS) and the cumulative incidence (CI) of transplantation-related mortality (TRM) and complications. Results:We report a probability of OS of 61%, a CI of TRM at day 100 and 365 post transplantation of 22% and 30%, respectively, and additionally a CI of graft failure, acute graft-versus-host disease (GvHD), and infectious complications, 18%, 44%, and 39%, respectively. No statistically significant association was detected between the above mentioned parameters and diagnosis, the use of myeloablative or nonmyeloablative/reduced toxicity conditioning regimens or the type of donor. Conclusions:We conclude that HSCT in infancy is associated with significant mortality and morbidity. This is possibly attributed to endogenous, age-related factors.More specifically, infants may be at a higher risk of toxicities due to the immaturity of developing vital organs and the deficiency of the newly adopted immune system that predisposes them to infectious complications. The development of GvHD further augments the danger of infections, in a potential vice-versa relationship. Moreover, there are few data on pharmacokinetics of chemotherapy agents, making safe and efficacious drug administration hard. How to cite this article: Oikonomopoulou C, Paisiou A, Ioannidou E-D, et al. Allogeneic hematopoietic stem cell transplantation in infants is associated with significant morbidity and mortality.

show abstract

“…Total leukocyte and lymphocyte counts were found to be comparable to healthy children after 1 year ( 21 ). However, flow cytometry investigations demonstrated that recovery of specific subsets might take much longer ( 22 ), CD3+, CD4+, CD8+ cells were affected most ( 23 – 25 ). Recovery of naive T cells to age-related normal levels was found to take 1-6 months ( 22 , 26 ), which can be explained by the ability of the thymus to produce new naive cells in childhood.…”

Section: Discussionmentioning

confidence: 99%

Baseline CD3+CD56+ (NKT-like) Cells and the Outcome of Influenza Vaccination in Children Undergoing Chemotherapy

et al. 2021

View full text Add to dashboard Cite

BackgroundIn children undergoing chemotherapy yearly influenza vaccination is recommended by treatment protocols. We investigated the relationship between cellular immunity and the antibody response to inactivated influenza vaccines.Methods25 patients (age: 2-18 years) undergoing chemotherapy for different malignancies participated in our study. Flow cytometric detection of peripheral blood lymphocyte subpopulations together with hemagglutination inhibition antibody titers were measured before and 21-28 days after vaccination. We examined the ratio and total numbers of CD3+, CD4+, CD8+ T cells, activated helper (CD3+CD4+CD25low), regulatory (CD3+CD4+CD25high), naive (CD3+CD45RA+) and memory (CD3+CD45RO+) T cells, CD56+NK, and CD3+CD56+ (NKT-like) cells. Relationships between specific antibody responses (seroprotection, seroconversion, geometric mean titer (GMT), geometric mean fold increase (GMFI)) and the ratios and counts of lymphocyte subpopulations were evaluated using one-way ANOVA and the paired sample t test after dichotomization according to age-related reference values.ResultsPatients with CD4+ lymphocyte levels in the normal age-specific range showed significantly better response regarding postvaccination GMT elevation for H1N1 and H3N2 strains (97.52 vs. 19.2, p=0.019, 80 vs. 14.43, p=0.021, respectively). GMFI results were significant only against B strain (2.69-fold vs. 1.23-fold, p=0.046). Prevaccination CD3+CD56+ (NKT-like) cells above predicted values according to age showed significant associations both in postvaccination GMT elevation (H1N1: 75.11 vs. 14.14, p=0.010; H3N2: 62.18 vs. 11.22, p=0.012; B: 22.69 vs. 6.67, p=0.043) and GMFI against all three strains (H1N1: 3.76-fold vs. 1.06-fold, p=0.015; H3N2: 2.74-fold vs. 1, p=0.013; B: 2.57-fold vs. 1, p=0.008). By one-way ANOVA, we found a positive relation between absolute lymphocyte cell count above 1000/µl and the postvaccination GMT elevation against H3N2 (12.81 vs. 56.56, p=0.032), and GMFI regarding H1N1 (1.22-fold vs. 3.48-fold, p=0.044).ConclusionsIn addition to verifying the predictive value of absolute lymphocyte count above 1000/µl, our results suggest an association between NKT-like cell counts and the specific antibody response against all three investigated influenza strains in highly immunosuppressed patients. Furthermore, prevaccination CD4+ lymphocyte levels in the normal age-specific range may influence seroresponse.

show abstract

Severe, persistent, and fatal T‐cell immunodeficiency following therapy for infantile leukemia

Cited by 12 publications

References 18 publications

A risk-stratified therapy for infants with acute lymphoblastic leukemia: a report from the JPLSG MLL-10 trial

A risk-stratified therapy for infants with acute lymphoblastic leukemia: a report from the JPLSG MLL-10 trial

Allogeneic hematopoietic stem cell transplantation in infants is associated with significant morbidity and mortality

Baseline CD3+CD56+ (NKT-like) Cells and the Outcome of Influenza Vaccination in Children Undergoing Chemotherapy

Contact Info

Product

Resources

About