Acral Skin Rash Caused by Altered Mercaptopurine Metabolism in Maintenance Therapy for B-Cell Acute Lymphoblastic Leukemia

Newcome, Jennifer; Geib, Kristen B; Thompson, Patrick A.; Gold, Stuart; Alexander, Thomas

doi:10.1097/mph.0000000000002434

Cited by 4 publications

(11 citation statements)

References 21 publications

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“…13 Studies have shown that 6MP is preferentially metabolized to its therapeutically active metabolite, 6TG, when allopurinol is used. 9,10,14 The combination of 6MP dose reduction with allopurinol has been shown to improve chemotoxic effects of hypoglycemia, hepatotoxicity, and recurrent pancreatitis. 11 A recent report demonstrated resolution in cutaneous lesions following utilization of the combination therapy as maintenance therapy of B-cell ALL.…”

Section: Discussionmentioning

confidence: 99%

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Chemotherapeutic metabolism presenting as a recalcitrant case of hand–foot syndrome and mucositis

Kwan,

Skokan,

Blesh-Boren

et al. 2024

J Oncol Pharm Pract

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Introduction Mercaptopurine (6MP) and methotrexate (MTX) are commonly used for maintenance chemotherapy for acute lymphoblastic leukemia (ALL). These medications have been associated with various side effects such as myelosuppression, colitis, and thyroiditis in addition to numerous cutaneous adverse events. Cutaneous side-effects most reported include mucositis, alopecia, xerosis, and pruritus. We report an interesting case of hand–foot syndrome to 6MP in a child on maintenance therapy for B-cell ALL from an alteration in medication metabolism. Case We report a 10-year-old male on maintenance chemotherapy for pre-Bcell ALL who presented to the hospital with worsening oral lesions and erythematous, fissured plaques on the palms and soles. Maintenance therapy consisted of IV vincristine and 5-day pulse of steroids every 12 weeks, daily 6MP, and weekly MTX, which were increased to ≥ 150% of standard dosing due to persistent absolute neutrophil counts > 1500. Metabolites obtained on admission demonstrated elevated 6MMP metabolites at 35,761 (normal < 5700). TPMT and NUDT15 enzyme activity were normal and no alterations in genotyping were discovered. Outcome Patient's oral chemotherapy, including both 6MP and MTX, were stopped and allopurinol 100 mg daily was initiated, which lead to overall improvement. Discussion Clinical findings of acute mucositis and worsening of hand–foot syndrome, in the setting of inadequate myelosuppression in a child on maintenance therapy for ALL should raise concerns to consider altered metabolism pathway leading to toxic metabolite buildup. Allopurinol can play in improving cutaneous manifestation and chemotherapeutic dosing in patients with altered metabolism.

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Section: Discussionmentioning

confidence: 99%

“…11 A recent report demonstrated resolution in cutaneous lesions following utilization of the combination therapy as maintenance therapy of B-cell ALL. 14…”

Section: Discussionmentioning

confidence: 99%

Chemotherapeutic metabolism presenting as a recalcitrant case of hand–foot syndrome and mucositis

Kwan,

Skokan,

Blesh-Boren

et al. 2024

J Oncol Pharm Pract

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“…5,6 The result of higher dosing and super shunting in ALL patients yields extraordinarily elevated 6-MMP and skin toxicity. 6,7 There is currently a paucity of information regarding this dermatologic reaction. Two publications, consisting of six cases total, have demonstrated similar findings in pediatric patients with ALL.…”

Section: Case Reportmentioning

confidence: 99%

Distal toxic acral erythema and mucositis secondary to 6‐mercaptopurine in a thiopurine methyltransferase “super shunter”

Smith,

Grove

2024

Pediatric Dermatology

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Toxic erythema of chemotherapy is a broad but useful diagnosis used to summate the non‐infectious, non‐allergic, and reproducible reaction of certain chemotherapeutics. Due to overlapping chemotherapy side effects and often multiple drug exposures, identification of a singular culprit drug is challenging for dermatologists. Herein, we report a patient with 6‐mercaptopurine (6‐MP) toxic erythema confirmed via toxic metabolite markers secondary to increased levels of thiopurine methyltransferase activity, or so called “super shunting.” Consulting dermatologists should be aware of “super shunting” in pediatric patients and consider testing for metabolites in patients with toxic acral erythema and mucositis in the setting of 6‐MP.

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“…[16] Furthermore, there have been recent advances in the formulation of mercaptopurine, such as the introduction of a long-acting version of the medicine, which may make it easier for patients to take and may improve its effectiveness. [17][18] These discoveries, however, are still in their early phases, and additional research is required before they can be extensively employed. Moreover, thiotepa has been used for many years to treat specific types of cancer, such as ovarian cancer and bladder cancer.…”

Section: Introductionmentioning

confidence: 99%

“…While mercaptopurine is not a novel medicine, there has been some recent research exploring its use for various purposes, such as the treatment of inflammatory bowel disease and autoimmune illnesses [16] . Furthermore, there have been recent advances in the formulation of mercaptopurine, such as the introduction of a long‐acting version of the medicine, which may make it easier for patients to take and may improve its effectiveness [17–18] . These discoveries, however, are still in their early phases, and additional research is required before they can be extensively employed.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Delivery Potential of Covalent Organic Framework (COF): Intuition from Theoretical Calculations

Mohammadi,

Louis,

Benjamin

et al. 2024

ChemistrySelect

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Regardless of the benefits, pharmaceutical companies are reticent to engage further in covalent organic framework‐based drug development and drug delivery systems, preferring rather to explore preexisting chemical compound libraries for drug delivery. As such, this study aims to account for the efficacy of covalent organic frameworks (COFs) in the delivery of seven conventional drugs: Acetaminophen, Clodronic Acid, Hydroxyurea, Mercaptoporine, Thiotepa, Tioguanine, and Arsenic trioxide. Herein, Gaussian 16 software package is employed for the purpose of optimizing the systems at the DFT/ωB97XD/def2svp level of theory. Substantially, the nature of the inter‐ and intra‐ molecular interactions between the COF and each of the drugs utilized resulted in the re‐adjustment of the molecular orbitals and yielded a distinct set of results for the most reactive and least stable and vice versa as deducible from the magnitudes of the highest occupied molecular orbital and lowest unoccupied molecular orbital (HOMO‐LUMO) gaps. Furthermore, the natural bond orbital (NBO) study indicates that the interacting molecules exhibit similar stability and reactivity, as evidenced by the proximity of their mean stabilization energies. Additionally, the topological analysis revealed that the most positive interaction occurred in Acetaminophen_COF, Clodronic acid_COF, Hydroxyurea_COF, and Tioguanine_COF. Also, the adsorption studies demonstrate that the above‐mentioned drugs have weak interaction kinetics when they interact with the investigated COF. Strong adsorbing contacts were detected in the interactions of Arsenic trioxide, Hydroxyurea, and Tioguanine with the COF in the order Arsenic trioxide_COF < Hydroxyurea_COF < Tiog_COF, with corresponding values of −9.413 kcal/mol, −12.550 kcal/mol, and −17.570 kcal/mol, respectively. Overall, the study hypothesizes that when delivering the various drugs studied through the COF to biological systems, Acetaminophen, Hydroxyurea, Tioguanine, and Mercaptopurine have high reactivity with the COF and would be better adsorbed on it, as well as a longer recovery time of desorption due to their high adsorption on the COF surface.

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Acral Skin Rash Caused by Altered Mercaptopurine Metabolism in Maintenance Therapy for B-Cell Acute Lymphoblastic Leukemia

Cited by 4 publications

References 21 publications

Chemotherapeutic metabolism presenting as a recalcitrant case of hand–foot syndrome and mucositis

Chemotherapeutic metabolism presenting as a recalcitrant case of hand–foot syndrome and mucositis

Distal toxic acral erythema and mucositis secondary to 6‐mercaptopurine in a thiopurine methyltransferase “super shunter”

Therapeutic Delivery Potential of Covalent Organic Framework (COF): Intuition from Theoretical Calculations

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