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A Pilot Study of the Combination of Retinoic Acid and Interferon-Alpha2a for the Treatment of Lymphoproliferative Disorders in Children With Immunodeficiency Syndromes

2014-08-27 03:59:35 | BioPortfolio

Summary

Patients with congenital or acquired immunodeficiencies are at an increased risk to develop polyclonal or oligoclonal lymphoid malignancies. Some develop a lymphoproliferative disorder that can follow a clinically aggressive course and may represent a pre-malignant lesion. Although most of these lymphoproliferative disorders are of B-cell origin, T-cell or non-B-non-T-cell processes have also been observed. The pathogenesis is only partially understood.

In the case of pre-malignant conditions it is often difficult to know when and whether a therapeutic intervention is necessary and a careful consideration of potential treatment-associated morbidity is indicated. Therapies have ranged from influencing the possible infectious etiology (by treating with acyclovir), decreasing the amount of immunosuppression (in transplant patients), to the use of immunomodulatory agents, including interferons and interleukins. Recent data have indicated that the use of differentiating agents, such as the retinoids, might offer yet another treatment option. In the current study we will try to get a better understanding of the pathogenesis and natural course of lymphoproliferative disorders in immunodeficient children.

The study will have two parts: an initial observation period to obtain information on the natural course of these disorders, and then a six month treatment period with the combination of a differentiating agent (13-cis-retinoic acid was used until all-trans-retinoic acid became available on 7/96) with an immunomodulatory agent (interferon-alpha2a, IFN-alpha2a).

Description

Patients with congenital or acquired immunodeficiencies are at an increased risk to develop polyclonal or oligoclonal lymphoid malignancies. Some develop a lymphoproliferative disorder that can follow a clinically aggressive course and may represent a pre-malignant lesion. Although most of these lymphoproliferative disorders are of B-cell origin, T-cell or non-B-non-T-cell processes have also been observed. The pathogenesis is only partially understood. The Epstein-Barr virus (EBV) is thought to play an important role but the human herpes virus type 6 (HHV-6) has been implicated as well. An imbalance in the expression of several cytokines is observed and it is currently not clear whether this sustains the aberrant proliferation or is a result thereof. In the case of pre-malignant conditions it is often difficult to know when and whether a therapeutic intervention is necessary and a careful consideration of potential treatment-associated morbidity is indicated. Therapies have ranged from influencing the possible infectious etiology (by treating with acyclovir), decreasing the amount of immunosuppression (in transplant patients), to the use of immunomodulatory agents, including interferons and interleukins. Recent data have indicated that the use of differentiating agents, such as the retinoids, might offer yet another treatment option. In the current study we will try to get a better understanding of the pathogenesis and natural course of lymphoproliferative disorders in immunodeficient children. The study will mainly be open to children infected with the human immunodeficiency virus but patients who develop a lymphoproliferative disorder post-transplant or as part of another immunodeficiency state may also be enrolled. The study will have two parts: an initial observation period to obtain information on the natural course of these disorders, and then a six month treatment period with the combination of a differentiating agent (13-cis-retinoic acid was used until all-trans-retinoic acid became available on 7/96) with an immunomodulatory agent (interferon-alpha2a, IFN-alpha2a).

Study Design

Endpoint Classification: Safety/Efficacy Study, Primary Purpose: Treatment

Conditions

HIV Infections

Intervention

all-trans-retinoic acid with IFN-alpha2a

Location

National Cancer Institute (NCI)
Bethesda
Maryland
United States
20892

Status

Completed

Source

National Institutes of Health Clinical Center (CC)

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:59:35-0400

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Medical and Biotech [MESH] Definitions

A cytochrome P450 enzyme that resides in the ENDOPLASMIC RETICULUM. It catalyzes the conversion of trans-RETINOIC ACID to 4-hydroxyretinoic acid.

Proteins in the nucleus or cytoplasm that specifically bind RETINOIC ACID or RETINOL and trigger changes in the behavior of cells. Retinoic acid receptors, like steroid receptors, are ligand-activated transcription regulators. Several types have been recognized.

A subtype of RETINOIC ACID RECEPTORS that are specific for 9-cis-retinoic acid which function as nuclear TRANSCRIPTION FACTORS that regulate multiple signalling pathways.

A metalloflavoprotein enzyme involved the metabolism of VITAMIN A, this enzyme catalyzes the oxidation of RETINAL to RETINOIC ACID, using both NAD+ and FAD coenzymes. It also acts on both the 11-trans- and 13-cis-forms of RETINAL.

A cytochrome P450 enzyme family whose members function in the metabolism of RETINOIC ACID. It includes RETINOIC ACID 4-HYDROXYLASE.

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