Reconstitution of peripheral blood lymphocyte subsets in the long-term disease-free survivors of patients with acute myeloblastic leukemia

Ohnishi, Kazunori; Yamanishi, Hiroaki; Kurio, Naito; Utsumi, Makoto; Yokomaku, S; Hirabayashi, Norio; Ohno, Ryuzo

doi:10.1038/sj.leu.2400891

Cited by 23 publications

(12 citation statements)

References 15 publications

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“…For example, in leukemia patients treated with chemotherapy, NK cell anti-leukemia cytotoxic activity has been directly correlated with disease-free-survival [39]. Several studies have also demonstrated the dynamic changes that occur in both quantitative and qualitative measures of humoral and cellular immunity during leukemia therapy, with effects extending from months to years following completion of therapy [39–42]. Two reports have identified an expanded oligoclonal population of activated regulatory T cells following hematopoietic recovery from intensive therapy in AML[43,44].…”

Section: Discussionmentioning

confidence: 99%

Absolute lymphocyte counts refine minimal residual disease‐based risk stratification in childhood acute lymphoblastic leukemia

Rabin

Gramatges

Borowitz

et al. 2011

Pediatric Blood & Cancer

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Background Several studies have demonstrated the prognostic utility of absolute lymphocyte count (ALC) during therapy for a range of malignancies, with low ALC associated with adverse outcome. Here we investigated whether ALC retained independent prognostic significance with respect to minimal residual disease (MRD) status in children with acute lymphoblastic leukemia (ALL). Procedure We reviewed 171 cases of pediatric ALL treated on the Children’s Oncology Group P9900 series of treatment trials. Variables analyzed included ALC at several time points during Induction, age at diagnosis, cytogenetics, initial white blood cell count, and MRD status at Day 29 of Induction (MRD-29). Results We found high ALC at Induction Day 29 (ALC-29) to be an independent, clinically significant predictor of improved relapse-free and overall survival. Patients with ALC-29 >1,500 cells/μL had a superior 6-year relapse-free survival (80±4% vs. 62±8%, p = 0.018) and overall survival (96±2% vs. 74±8%, p = 0.001). Moreover, ALC-29 identified distinct prognostic subgroups within cases stratified by MRD-29. In subjects with >0.01% MRD, ALC-29 > or < 1,500 cells/μL had a significant 51% difference in 6-year overall survival (92±7% vs. 41±16%, p = 0.0001). Conclusions ALC, a readily obtainable test, constitutes a significant and independent prognostic factor in childhood ALL that may refine current MRD-based risk stratification algorithms and provide key prognostic information in settings where MRD determination is not feasible.

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Section: Discussionmentioning

confidence: 99%

Absolute lymphocyte counts refine minimal residual disease‐based risk stratification in childhood acute lymphoblastic leukemia

Rabin

Gramatges

Borowitz

et al. 2011

Pediatric Blood & Cancer

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“…While the thymus plays a role in PBL reconstitution, 37,38 eventual recovery of CD4 ϩ T cells is thought to be largely thymic independent. [38][39][40] Although our data do show that most early recovering PBLs are peripherally derived, surprisingly, most patients, regardless of age, show a burst of appreciable thymopoiesis during early PBL recovery.…”

Section: Discussionmentioning

confidence: 99%

Early lymphocyte recovery after intensive timed sequential chemotherapy for acute myelogenous leukemia: peripheral oligoclonal expansion of regulatory T cells

Kanakry¹,

Hess

Gocke

et al. 2011

Blood

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Few published studies characterize early lymphocyte recovery after intensive chemotherapy for acute myelogenous leukemia (AML). To test the hypothesis that lymphocyte recovery mirrors ontogeny, we characterized early lymphocyte recovery in 20 consecutive patients undergoing induction timed sequential chemotherapy for newly diagnosed AML. Recovering T lymphocytes were predominantly CD4 ؉ and included a greatly expanded population of CD3 ؉ CD4 ؉ CD25 ؉ Foxp3 ؉ T cells. Recovering CD3 ؉ CD4 ؉ CD25 ؉ Foxp3 ؉ T cells were phenotypically activated regulatory T cells and showed suppressive activity on cytokine production in a mixed lymphocyte reaction. Despite an initial burst of thymopoiesis, most recovering regulatory T cells were peripherally derived. Furthermore, regulatory T cells showed marked oligoclonal skewing, suggesting that their peripheral expansion was antigen-driven. Overall, lymphocyte recovery after chemotherapy differs from ontogeny, specifically identifying a peripherally expanded oligoclonal population of activated regulatory T lymphocytes. These differences suggest a stereotyped immunologic recovery shared by patients with newly diagnosed AML after induction timed sequential chemotherapy. Further insight into this oligoclonal regulatory T-cell population will be fundamental toward developing effective immunomodulatory techniques to improve survival for patients with AML. (Blood. 2011;117(2):608-617)

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“…So whether ALC after therapy reflects the actual hematopoietic recovery remains unclear; (3) various ALC cut-off values and time points have caused difficulties in clinical practice, thus it is necessary to find more appropriate and simpler prognostic indicators to overcome the diversity; (4) natural killer (NK) cells and T cells have been shown to target hematopoietic malignancies and play an important role in maintaining remission [22][23][24], however, it is unclear whether ALC is associated with T cells, NK cells or even B cells responsible for its effect. Notably, in our previous study, we showed that higher ALC at interim of the induction therapy is significantly correlated with lower MRD level at interim of therapy in childhood B-ALL [25].…”

Section: Introductionmentioning

confidence: 99%

The ratio of absolute lymphocyte count at interim of therapy to absolute lymphocyte count at diagnosis predicts survival in childhood B-lineage acute lymphoblastic leukemia

et al. 2015

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Reconstitution of peripheral blood lymphocyte subsets in the long-term disease-free survivors of patients with acute myeloblastic leukemia

Cited by 23 publications

References 15 publications

Absolute lymphocyte counts refine minimal residual disease‐based risk stratification in childhood acute lymphoblastic leukemia

Absolute lymphocyte counts refine minimal residual disease‐based risk stratification in childhood acute lymphoblastic leukemia

Early lymphocyte recovery after intensive timed sequential chemotherapy for acute myelogenous leukemia: peripheral oligoclonal expansion of regulatory T cells

The ratio of absolute lymphocyte count at interim of therapy to absolute lymphocyte count at diagnosis predicts survival in childhood B-lineage acute lymphoblastic leukemia

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