Severe cutaneous ulceration following treatment with thalidomide for GVHD

Schlossberg, H. R.; Tr, Klumpp; P, Sabol; Herman, Jay H.; Mangan, Kenneth F.

doi:10.1038/sj.bmt.1702756

Cited by 11 publications

(3 citation statements)

References 3 publications

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“…Furthermore, they suggested a link between ulcer formation and regression of sclerosis. Thalidomide has also been related to skin ulcers 16 as well as the emergence or worsening of sclerosis. 17 While it is difficult to absolutely exclude the role of drugs, the chronology of the ulcers in our cases makes this unlikely.…”

Section: Discussionmentioning

confidence: 99%

Skin ulcers related to chronic graft-versus-host disease: clinical findings and associated morbidity

et al. 2014

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Section: Discussionmentioning

confidence: 99%

Skin ulcers related to chronic graft-versus-host disease: clinical findings and associated morbidity

et al. 2014

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“…Thalidomide should not however be considered in patients with preexisting neuropathy and the associated sedative effects and constipation may not be well tolerated (5). However, caution should be taken as Schlossberg et al reported two cases of severe leg ulceration in patients treated with thalidomide for SGVHD (11). They proposed that the etiology of this ulceration was secondary to the anti- angiogenic properties of thalidomide and urged careful attention to skin breakdown in SGVHD on this drug.…”

Section: Discussionmentioning

confidence: 99%

Sclerodermatous Chronic Graft‐Versus‐Host Disease—A Report of Four Pediatric Cases

Tolland

Devereux

Jones

et al. 2008

Pediatric Dermatology

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The sclerodermatous variant of chronic graft-versus-host disease postallogeneic bone marrow transplantation is rare. We present four pediatric cases of sclerodermatous variant of chronic graft-versus-host disease describing their clinical appearance, management, and outcomes. We compare the pharmacologic and supportive therapies administered to these patients with the management suggested in the current literature. Several key findings were noted. There was a significantly higher mortality rate observed in this series compared with previous reports, with three of the four patients dying ultimately as a result of sclerodermatous variant of chronic graft-versus-host disease. The development of widespread ulceration, in two of the four patients, appeared to be associated with an overall deterioration in the clinical condition. In two patients high-dose thalidomide at 12 mg/kg/day seemed to halt the progression of cutaneous disease. Optimal care of sclerodermatous variant of chronic graft-versus-host disease patients required a multidisciplinary team. A lack of community services observed in this case series led to the need for unnecessarily prolonged inpatient admissions.

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“…It is likely that the neuropathy leads to non-perceived repetitive trauma, and exacerbates the inadequate blood supply associated with cGVHD. Schlossberg et al 2 reported two cases of severe bilateral leg ulcers following treatment of skin GVHD with thalidomide. Although these lesions were present before initiating thalidomide, they were exacerbated by the drug, and it is possible that this worsening was a consequence of thalidomide-associated sensory neuropathy.…”

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confidence: 99%

Neuropathic dermatomes and cutaneous ulceration in patients with chronic GVHD

Kamble

Scholoff

et al. 2014

Bone Marrow Transplant

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We report two cases of severe ulcerative cutaneous chronic GVHD (cGVHD) that involved areas of sensory loss. The report highlights the importance of meticulous wound care and injury prevention measures to reduce the risk of this complication.Patient #1 is a 56-year-old African-American female who received an allogeneic transplant using matched related donor PBSCs in February 2009 as treatment for stage IVB diffuse large B-cell lymphoma who had failed initial therapy with R-CHOP in 2005, and then relapsed after a salvage regimen of rituximab, ifosphamide, cisplatin and etoposide followed by carmustine, etoposide, cytosine arabinoside, melphalan and rituximab with autologous SCT in 2006. Before her allogeneic transplant, she received fully ablative conditioning with 60 mg/kg/day for 2 days of CY and TBI (1200 cGy), and tacrolimus (targeted to 10 μg/L) and methotrexate (5 mg/m 2 on day +1, +6, +9 and +11) were used as GVHD prophylaxis. Neutrophil and platelet engraftment were on days 17 and 11, respectively and blood STRs confirmed 100% donor chimerism by day 17. On day 31 she developed, grade III acute GVHD with diffuse rash, liver enzyme elevation and diarrhea; colonoscopy and biopsy confirmed acute GVHD (aGVHD). With tapering steroid therapy, aGvHD improved but she continued on 10 mg prednisone daily.From day 100 onward, she complained of sensory loss of subacute onset below both knees. An electron myography and nerve conduction (EMG-NC) study revealed decreased sensory responses in the right sural nerve and superficial peroneal nerve; but a left-sided study could not be performed owing to extensive and multiple cutaneous ulcers that developed from day 150 onward (Figure 1). Although the patient had received XRT (36 cGy over 20 fractions) to a left inguinal mass in 2006, no cause for the bilateral neuropathy could be determined; however, the histology of biopsies from the ulcers was consistent with that of GVHD. Subsequently, four apparently identical ulcers appeared on the right leg. Oral prednisone was continued at 10 mg and she was given standard wound care. Although these lesions have persisted for~3 years, they are slowly improving without surgical intervention. 1 At her 60-month follow-up, the patient remains in CR.Patient #2 is a 24-year-old Caucasian female who received an HLA-matched related donor PBSC transplant in August 2009 after entering CR2 of AML with diploid cytogenetics. Conditioning was with BU/CY (BU 0.8 mg/kg every 6 h × 4days with blood levels, CY 60 mg/kg/day for 2 days) and she received tacrolimus (targeted to 10 μg/L) and MTX (5 mg/m 2 on day +1, +6, +9 and +11) as GVHD prophylaxis. Following engraftment, she developed grade I aGVHD that resolved after treatment with prednisone. She had no cGvHD. Unfortunately, 35 months later, she relapsed with isolated meningeal disease and a left ileopsoas granulocytic sarcoma (GS), which produced a motor deficit and sensory loss affecting the L4/5 nerve root distribution (left upper lateral thigh and knee). BM biopsy was negative for disease. She rec...

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Severe cutaneous ulceration following treatment with thalidomide for GVHD

Cited by 11 publications

References 3 publications

Skin ulcers related to chronic graft-versus-host disease: clinical findings and associated morbidity

Skin ulcers related to chronic graft-versus-host disease: clinical findings and associated morbidity

Sclerodermatous Chronic Graft‐Versus‐Host Disease—A Report of Four Pediatric Cases

Neuropathic dermatomes and cutaneous ulceration in patients with chronic GVHD

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