Early Lymphocyte Recovery as a Prognostic Indicator for High-risk Ewing Sarcoma

Angulo, Guillermo De; Hernandez, Mike; Morales-Arias, Jaime; Herzog, Cynthia E.; Anderson, Peter M.; Wolff, Johannes; Kleinerman, Eugenie S.

doi:10.1097/mph.0b013e31802d3e3e

Cited by 63 publications

(51 citation statements)

References 13 publications

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“…We and others have shown that many standard cytotoxic regimens for cancer induce profound prolonged alterations in T-cell number, function and repertoire diversity (15,16). Numerous correlative studies link lymphocyte depletion with adverse outcomes in cancer, (18)(19)(20)(21)(22)(23)(25)(26)(27)(28) and animal models demonstrate diminished sarcoma metastases following immune reconstitution (31). These facts raise the dual possibilities that tumor recurrence may be enhanced by cancer therapy-induced immune depletion and that immunotherapies administered to lympho-depleted hosts might prove effective at eradicating less immune sculpted residual cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…Standard cytotoxic regimens administered for pediatric sarcomas incorporate highdose alkylators and induce profound, prolonged lymphocyte depletion (15)(16)(17). Several studies demonstrate correlations between lymphopenia and diminished survival in cancer (18)(19)(20)(21)(22)(23)(24)(25)(26), including ES (27,28), but it remains unclear whether lymphopenia plays a causal role in this observation. Numerous animal studies demonstrate that naturally acquired immune responses contribute to control of cancer (29,30), and in a murine model of osteosarcoma, lymphopenia enhanced metastatic recurrence, whereas immune reconstitution diminished metastatic recurrence (31).…”

Section: Introductionmentioning

confidence: 99%

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Adjuvant Immunotherapy to Improve Outcome in High-Risk Pediatric Sarcomas

Merchant

Bernstein

Amoako

et al. 2016

Clinical Cancer Research

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Purpose: Patients with metastatic or relapsed pediatric sarcomas receive cytotoxic regimens that induce high remission rates associated with profound lymphocyte depletion, but ultimately few survive long term. We administered adjuvant immunotherapy to patients with metastatic and recurrent pediatric sarcomas in an effort to improve outcomes.Experimental Design: Mononuclear cells were collected via apheresis, and tumor lysate was acquired via percutaneous biopsy at enrollment. Participants received standard antineoplastic therapy, followed by autologous lymphocytes, tumor lysate/keyhole limpet hemocyanin-pulsed dendritic cell vaccinations AE recombinant human IL7. Primary outcomes were toxicity and vaccine responses. Secondary outcomes were immune reconstitution, event-free survival, and overall survival (OS).Results: Forty-three patients enrolled and 29 received immunotherapy. The regimen was well tolerated. Intent-to-treat analysis demonstrated 5-year OS of 51% with significant differences based upon histologic group (63% vs. 0% for Ewing/ rhabdomyosarcoma vs. other sarcomas) and response to standard therapy (74% no residual disease vs. 0% residual disease). Five-year intent-to-treat OS of patients with newly diagnosed metastatic Ewing/rhabdomyosarcoma was 77%, higher than previously reported in this population and higher than observed in a similar group treated with an earlier adjuvant immunotherapy regimen (25% 5-year OS). T-cell responses to autologous tumor lysate were identified in 62% of immunotherapy recipients, and survival was higher in those patients (73% 5-year OS with vs. 37% without immune response, P ¼ 0.017). Immune reconstitution, measured by CD4 count recovery, was significantly enhanced in subjects treated with recombinant human IL7.Conclusions: Adjuvant immunotherapy may improve survival in patients with metastatic pediatric sarcoma. Clin Cancer Res; 22(13); 3182-91. Ó2016 AACR.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Adjuvant Immunotherapy to Improve Outcome in High-Risk Pediatric Sarcomas

Merchant

Bernstein

Amoako

et al. 2016

Clinical Cancer Research

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“…In addition, we also demonstrated the predictive ability of ALC in Ewing sarcoma, a bone tumor. 41 Similarly, we have discovered that this predictive ability holds true for young patients with non-Hodgkin lymphoma (unpublished data, G. De Angulo). These studies, when combined with several studies in adults by Porrata et al and Behl et al, suggest that there is a generalized posttherapy ALC phenomenon, relevant to a wide range of malignancies and ages.…”

Section: Alc As a Prognostic Factor In A Range Of Malignanciesmentioning

confidence: 98%

Absolute lymphocyte count is a novel prognostic indicator in ALL and AML

Angulo¹,

Yuen²,

Palla³

et al. 2007

Cancer

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112

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BACKGROUND.Leukemia is the leading cause of disease‐related death in children, despite significant improvement in survival and modern risk stratification. The prognostic significance of absolute lymphocyte counts (ALC) was evaluated in young patients with acute myeloblastic leukemia (AML) and acute lymphoblastic leukemia (ALL).METHODS.In all, 171 consecutive de novo cases of AML and ALL, age ≤21 years, were analyzed. Age, initial white blood cell count, cytogenetics, and bone marrow response were compared with lymphocyte, neutrophil, and platelet counts at weekly intervals during induction chemotherapy.RESULTS.ALC is a significant independent predictor of relapse and survival. For example, in patients with AML an ALC on Day 28 of induction (ALC‐28) <350 cells/μL predicts very poor survival, with a 5‐year relapse‐free survival (RFS) of only 10% (hazard ratio [HR] 3.7, P = .003). In contrast, an ALC‐15 >350 cells/μL carries an excellent prognosis, with a 5‐year overall survival (OS) of 85% (HR 0.2, P = .012). Similarly in ALL, an ALC‐15 <350 cells/μL predicts poor survival, with a 6‐year RFS of 43% (HR 4.5, P = .002), whereas an ALC‐15 >350 cells/μL predicts excellent outcome, with a 6‐year OS of 87% (HR 0.2, P = .018). Importantly, ALC remains a strong predictor in multivariate analysis with known prognostic factors.CONCLUSIONS.ALC is a simple, statistically powerful measurement for patients with de novo AML and ALL. The results, when combined with previous studies, demonstrate that ALC is a powerful new prognostic factor for a range of malignancies. These findings suggest a need for further exploration of postchemotherapy immune status and immune‐modulating cancer therapies. Cancer 2008. © 2007 American Cancer Society.

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“…[20]. In pediatric patients with Ewing sarcoma that achieved an ALC at day 15 after initial chemotherapy, treatment of ≥500 cells/µL had a 3-year overall survival of 68% compared with 32% for patients with an ALC < 500 cells/µL at day 15 after initial chemotherapy treatment [21,22]. In NHL patients that relapse after standard chemotherapy, higher ALC at the time of relapse has been associated with better clinical outcome and survival after further treatment has been implemented after relapse [23,24].…”

Section: Absolute Lymphocyte Count and Chemotherapymentioning

confidence: 99%

Is Absolute Lymphocyte Count Just Another Prognostic Factor in Cancer?

Porrata¹,

Markovic²

2010

SRX Medicine

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The role of host immunity in cancer clinical outcomes has been wellestablished in animal models. In humans, the impact of the immune system as a therapeutic maneuver to treat malignancies has been proven by the development of graft-versus-tumor effect observed in the allogeneic stem cell transplantation. However, with few notable exceptions, no definitive conclusions have been reached as to the role of host immunity in humans and its impact on cancer outcomes. This article reviews the clinical evidence of how human immunity can affect cancer clinical outcomes using the absolute lymphocyte count as a surrogate maker of host immune competence.

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Early Lymphocyte Recovery as a Prognostic Indicator for High-risk Ewing Sarcoma

Abstract: The data demonstrate that an ALC > or =500 cells/microL on day 15 of the first course of chemotherapy is an independent prognostic factor associated with superior OS in high-risk Ewing sarcoma.

Cited by 63 publications

References 13 publications

Adjuvant Immunotherapy to Improve Outcome in High-Risk Pediatric Sarcomas

Adjuvant Immunotherapy to Improve Outcome in High-Risk Pediatric Sarcomas

Absolute lymphocyte count is a novel prognostic indicator in ALL and AML

Is Absolute Lymphocyte Count Just Another Prognostic Factor in Cancer?

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