Successful Healing of Hydroxyurea-Related Leg Ulcers With Topical Granulocyte-Macrophage Colony-Stimulating Factor

Stagno, Fabio; Guglielmo, Patrizia; Consoli, Ugo; Fiumara, Paolo; Russo, Mario Salvatore; Giustolisi, Rosario

doi:10.1182/blood.v94.4.1479

Cited by 32 publications

(23 citation statements)

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“…1 Leg ulcers have recently been reported as a rare complication of HU treatment. [2][3][4][5][6] Leg ulcers induced by HU have common features; most are localized to the malleolar region, are extremely painful, and are refractory to meticulous wound care. [2][3][4][5][6] They usually develop after long-term HU therapy and their resolution usually requires its discontinuation.…”

Section: Discussionmentioning

confidence: 99%

“…[2][3][4][5][6] Leg ulcers induced by HU have common features; most are localized to the malleolar region, are extremely painful, and are refractory to meticulous wound care. [2][3][4][5][6] They usually develop after long-term HU therapy and their resolution usually requires its discontinuation. [2][3][4][5] The clinical characteristics of our three patients were similar to those previously reported (Table 1).…”

Section: Discussionmentioning

confidence: 99%

“…[2][3][4][5][6] They usually develop after long-term HU therapy and their resolution usually requires its discontinuation. [2][3][4][5] The clinical characteristics of our three patients were similar to those previously reported (Table 1). Unfortunately, the cessation of HU therapy was not possible in our patients, as an alternative drug, anagrelide, is not available in Turkey.…”

Section: Discussionmentioning

confidence: 99%

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Leg ulcers and hydroxyurea: report of three cases with essential thrombocythemia

2002

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CASE 1: A 65-year-old woman with essential thrombocythemia (ET) had been taking oral hydroxyurea (HU), 1,000 mg daily, for 7 years. Six months ago, she developed an ulcer on the outer part of her left ankle, which healed spontaneously within 2 months. She presented with a new, tender, shallow ulcer, 2 cm x 2 cm in size, at the same site. Doppler examination revealed thrombosis of the left common femoral vein and a calcified atheroma plaque of the left common femoral artery. The dosage of HU was decreased to 500 mg daily when the platelet counts were found to be within normal levels. The ulcer completely healed within 2 months with occlusive wound dressings, and has not recurred within the follow-up period of 1 year. CASE 2: A 56-year-old women presented with multiple, painful, leg ulcers of 1 year duration. She had been diagnosed as having ET and had been on HU therapy, 1,500 mg/day, for the past 5 years. Interferon-alpha-2b was started 3 months ago, in addition to HU, which was tapered to 1,000 mg daily. She had suffered from hypertension for 20 years treated with nifedipine and enalapril, and had recently been diagnosed with diabetes mellitus which was controlled by diet. Examination revealed three ulcers located on the lateral aspects of both ankles and right distal toe. Arterial and venous Doppler examinations were within normal limits. Histopathology of the ulcer revealed nonspecific changes with a mixed inflammatory cell infiltrate around dermal vessels. The ulcers completely healed within 10 weeks with topical hydrocolloid dressings. After healing, she was lost to follow-up. A year later, it was learned that she had developed a new ulcer at her right heel, 3 months after her last visit (by phone call). This ulcer persisted for 8 months until HU was withdrawn. CASE 3: A 64-year-old woman with ET presented with a painful leg ulcer of 6 months' duration. She had been taking oral HU for 5 years. She had a 20-year history of hypertension treated with lisinopril. Examination revealed a punched-out ulcer of 2 cm x 2 cm over the right lateral malleolus. Doppler examination of the veins revealed insufficiency of the right greater saphenous and femoral veins. Angiography showed multiple stenoses of the right popliteal and femoral arteries. As her platelet count remained high, HU was continued. During the follow-up period of 13 months, the ulcer showed only partial improvement with local wound care.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Leg ulcers and hydroxyurea: report of three cases with essential thrombocythemia

2002

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“…Among them, painful skin ulcers have been reported for many years in several single cases or unicentric small cohorts of patients. [10][11][12][13][14][15][16][17][18][19][20][21][22] Currently, the occurrence of skin ulcers during HU treatment is considered a treatment failure 24 ; nonetheless, a full and specific evaluation of symptomatic mucocutaneous toxicity during HU treatment in a large multicentric study focusing on incidence, clinical features, and follow-up is still lacking.…”

Section: Discussionmentioning

confidence: 99%

“…The occurrence of painful leg ulcers is a rare complication that has been described in patients receiving highdose, long-term HU treatment, often leading to drug discontinuation. 9 To the best of our knowledge, to date only single case reports [10][11][12][13][14][15][16][17][18] or single-center experiences [19][20][21][22] have been published regarding this phenomenon, with a reported incidence ranging from 5% to 10% of the treated patients. A 5% incidence of skin ulcers during HU treatment also has been reported in a large randomized trial in patients with essential thrombocythemia.…”

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confidence: 99%

Symptomatic mucocutaneous toxicity of hydroxyurea in Philadelphia chromosome‐negative myeloproliferative neoplasms

Latagliata

Spadea

Cedrone³

et al. 2011

Cancer

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SMPC Ph1 neg BACKGROUND:The current study was conducted to evaluate severe mucocutaneous toxicity during treatment with hydroxyurea (HU) in a large cohort of patients with Philadelphia chromosome-negative myeloproliferative neoplasms (MPN). METHODS: Among 993 consecutive patients newly diagnosed with MPN at 4 centers in Rome between January 1980 and December 2009, 614 patients (277 men and 337 women with a median age of 64.4 years [interquartile range (IR), 54.4 years-72.7 years]) received HU. HU was administered as first-line treatment in 523 patients (85.2%) and as ! second-line treatment in 91 patients (14.8%). RESULTS: Mucocutaneous toxicity was reported in 51 patients (8.3%) after a median period from the initiation of HU treatment of 32.1 months (IR, 10.5 months-74.6 months) and a mean HU dose of 1085 mg (AE 390 mg); 30 patients (58.8%) developed a painful ulcerative skin toxicity, mainly located in the perimalleolar area; 11 patients (21.6%) had oral aphthous ulcers; and 10 patients (19.6%) developed a nonulcerative skin toxicity with erythema and skin infiltration. After the mucocutaneous toxicity occurred, HU treatment was continued at the same dose in 5 patients (9.8%), reduced in 12 patients (23.5%), and temporarily discontinued in 7 patients (13.7%); the remaining 27 patients (52.9%) required a permanent drug discontinuation. After a median period of 4.3 months (IR, 2.4 months-9.0 months) from the onset of the skin toxicity, 39 patients (76.5%) had a complete resolution and 12 patients (23.5%) had improvement without complete resolution. CONCLUSIONS: Mucocutaneous toxicity during HU treatment is more common than expected and may present with different clinical features. Moreover, it often requires a permanent drug discontinuation and only a partial resolution is reported to occur in approximately 25% of patients. Cancer 2012;118:404-

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Granulocyte–Macrophage Colony‐Stimulating Factor for Treating Gastrostomy Tube Site Healing in a Child With Glycogen Storage Disease Type Ib

Steinmetz,

Martin,

Roberts

2001

J. pediatr. gastroenterol. nutr.

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Successful Healing of Hydroxyurea-Related Leg Ulcers With Topical Granulocyte-Macrophage Colony-Stimulating Factor

Cited by 32 publications

References 7 publications

Leg ulcers and hydroxyurea: report of three cases with essential thrombocythemia

Leg ulcers and hydroxyurea: report of three cases with essential thrombocythemia

Symptomatic mucocutaneous toxicity of hydroxyurea in Philadelphia chromosome‐negative myeloproliferative neoplasms

Granulocyte–Macrophage Colony‐Stimulating Factor for Treating Gastrostomy Tube Site Healing in a Child With Glycogen Storage Disease Type Ib

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