RESUMEN
BACKGROUND: Mantle cell lymphoma (MCL) is aggressive, and relapsed/refractory disease has poor outcomes. PATIENTS AND METHODS: Thirty-nine patients (men = 34, women = 5) at 64 (41-82) years of age with relapsed/refractory MCL, ineligible for high-dose chemotherapy and had received 2 (1-5) prior regimens, were treated with a continuous oral regimen, comprising oral arsenic trioxide (oral-As2O3), chlorambucil and ascorbic acid. RESULTS: Overall response rate was 49% (complete response, CR = 28%; partial response, PR = 21%). Only grade 1/2 toxicities were observed (hematologic: 56%, hepatic: 8%). Response was maintained in 11 patients (CR = 8; PR = 3), after a median of 24 (2-108) months. Independent prognostic factors for response were increased lactate dehydrogenase (P = 0.04) and unfavorable MCL international prognostic index (P = 0.04). At a median follow-up of 21 (1-118) months, the median progression-free survival (PFS) was 16 months, and overall survival (OS) 38 months. Independent prognostic factors for PFS were female gender (P = 0.002), and Eastern Cooperative Oncology Group (ECOG) performance score of 2 (P = 0.009). Independent prognostic factors for OS were female gender (P < 0.001), ECOG performance score of 2 (P = 0.03), non-response (P < 0.001), and disease progression after initial response (P = 0.05). CONCLUSION: An oral regimen of oral-As2O3, chlorambucil and ascorbic acid was active with minimal toxicity in relapsed/refractory MCL, achieving durable responses in â¼30% of cases.
Asunto(s)
Arsenicales/uso terapéutico , Linfoma de Células del Manto/tratamiento farmacológico , Óxidos/uso terapéutico , Terapia Recuperativa , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Trióxido de Arsénico , Arsenicales/administración & dosificación , Humanos , Linfoma de Células del Manto/diagnóstico por imagen , Persona de Mediana Edad , Óxidos/administración & dosificación , Tomografía de Emisión de Positrones , Recurrencia , Análisis de SupervivenciaRESUMEN
Cough mixture abuse is an emerging problem among young men in Oriental countries. Its metabolic consequences have been recognised only recently. Such abusers can develop severe folate deficiency, which may be related to peripheral and central nervous system defects. We report three cough mixture abusers with rhabdomyolysis. All suffered from folate deficiencies and also had a history of anti-psychotic drug use. This represents one more life-threatening side-effect from cough mixture abuse.
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Antitusígenos/efectos adversos , Rabdomiólisis/inducido químicamente , Trastornos Relacionados con Sustancias/complicaciones , Adulto , Antipsicóticos/efectos adversos , Femenino , Deficiencia de Ácido Fólico/inducido químicamente , Deficiencia de Ácido Fólico/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenAsunto(s)
Trasplante de Células Madre Hematopoyéticas , Inmunosupresores/administración & dosificación , Donadores Vivos , Mieloma Múltiple/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiología , Talidomida/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trasplante HomólogoRESUMEN
Arsenic trioxide has been used in traditional Chinese medicine for over 5000 years, but lost its appeal due to its toxicity. It was rediscovered in western medicine and enjoyed a renaissance from 1830 to 1930, as the first effective chemotherapy against syphilis, parasites and leukaemia. These years were also a time of political turmoil in China. The Nanking treaty (29 August 1842) turned Hong Kong into a colony, while the Xinhai Revolution (10 October 1911) gave birth to a republic of China. Arsenic returned to China and Hong Kong with the establishment of the first medical schools from 1887 to 1920. Until 1950, oral arsenic trioxide was the standard anti-leukaemic treatment in Queen Mary Hospital. The advent of alkylating chemotherapeutic agents replaced arsenic trioxide in Hong Kong and around the world. In the 1970s, however, the specific activity of arsenic trioxide against acute promyelocytic leukaemia was re-discovered during the Cultural Revolution in Harbin, China. In 1997, Hong Kong was returned to China. In the same year, arsenic trioxide returned to the world stage. Intravenous arsenic trioxide became the worldwide standard therapy for relapsed acute promyelocytic leukaemia. Oral administration of arsenic trioxide was revived in Hong Kong in 2000. This resulted in the first locally produced, registered, patented prescription drug in Hong Kong. Pending imminent manufacture, this product is poised to revolutionise acute promyelocytic leukaemia care and may hold the key to saving the lives of acute promyelocytic leukaemia patients worldwide. The remarkable journey of arsenic in the setting of medical history of China and Hong Kong is reviewed.
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Arsénico/historia , Medicina Tradicional China/historia , China , Historia del Siglo XVI , Historia del Siglo XVIII , Historia del Siglo XIX , Historia del Siglo XX , Historia del Siglo XXI , Historia Antigua , Hong Kong , HumanosRESUMEN
OBJECTIVE: To provide a synopsis of current thalassaemia major patient care in Hong Kong. DESIGN: Retrospective study. SETTING: All haematology units of the Hospital Authority in Hong Kong. PATIENTS: All patients with thalassaemia major with regular transfusion. RESULTS: To date, there were 363 thalassaemia major patients under the care of the Hospital Authority. Prenatal diagnosis has helped to reduce the number of indigenous new cases, but in recent years immigrant cases are appearing. The patients have a mean age of 23 (range, 1-52) years, and 78% of them are adults. In 2009, they received 18 782 units of blood. This accounted for 9.5% of all blood consumption from the Hong Kong Red Cross. In the past, cardiac iron overload was the major cause of death (65%) and few patients survived beyond the age of 45 years. The availability of cardiac iron assessment by magnetic resonance imaging (T2 MRI) to direct the use of oral deferiprone chelation has reduced the prevalence of heart failure and cardiac haemosiderosis, which should reduce mortality and improve life expectancy. CONCLUSION: The future for thalassaemia care in Hong Kong is bright. With better transfusion and chelation, it should be possible to avoid growth and endocrine deficiencies in younger patients.
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Talasemia/terapia , Adolescente , Adulto , Niño , Preescolar , Transfusión de Eritrocitos , Hong Kong , Humanos , Lactante , Sobrecarga de Hierro/etiología , Persona de Mediana Edad , Osteoporosis/etiología , Estudios Retrospectivos , Talasemia/complicaciones , Talasemia/mortalidadRESUMEN
OBJECTIVE: To provide a synopsis of current haemophilia care in Hong Kong. DESIGN: Retrospective survey. SETTING: All haematology units of the Hospital Authority in Hong Kong. PATIENTS: All patients with haemophilia A and haemophilia B. RESULTS: To date, there were 222 mild-to-severe haemophilia patients (192 type A, 30 type B) under regular public care in Hong Kong (43% were considered severe, 33% moderate, and 24% mild), which gave a crude prevalence of 6.8/100 000 male inhabitants. A total of 12.8 million units of Factor VIII and 3 million units of Factor IX were prescribed annually. This amounts to 1.83 units of FVIII per capita of the population, which is comparable to that of other developed countries. Leading causes of mortality were human immunodeficiency virus-related complications (10 cases) and cerebral bleeding (2 cases). The life expectancy of patients with severe haemophilia in Hong Kong is improving; currently the oldest patient is 60 years old. Such improved survival may be due to enhanced factor availability, prompt treatment of bleeding episodes at home, safer factor products, and better antiviral treatment. Primary prophylaxis is the accepted standard of care for severe and moderate cases, and "Factor First" has become hospital policy. However, 12 patients continue to present treatment challenges, due to the documented presence of factor inhibitors. In all, 28, 100, and 14 cases respectively were positive for human immunodeficiency virus, hepatitis C virus, and hepatitis B virus; the youngest patients with the corresponding infections being 28, 13, and 22 years old. Comprehensive care with dedicated physiotherapy, surgical support, and radionucleotide synovectomy may reduce morbidity further. CONCLUSION: A multidisciplinary approach can further improve the future care for haemophilia patients in Hong Kong.
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Coagulantes/uso terapéutico , Hemofilia A/terapia , Hemofilia B/terapia , Adolescente , Adulto , Anciano , Niño , Preescolar , Factor IX/uso terapéutico , Factor VIII/uso terapéutico , Hemofilia A/epidemiología , Hemofilia A/fisiopatología , Hemofilia B/epidemiología , Hemofilia B/fisiopatología , Hong Kong/epidemiología , Humanos , Lactante , Esperanza de Vida , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
Bronchiolitis obliterans syndrome (BOS) is an important complication after hematopoietic SCT (HSCT). Recent observations suggested that azithromycin might improve lung function in BOS after HSCT. We conducted a randomized double-blinded placebo-controlled study on azithromycin in patients with BOS after HSCT. The treatment group (n=10) received oral azithromycin 250 mg daily while the control group (n=12) received placebo daily for 12 weeks. Respiratory symptoms were assessed by the St George Respiratory Questionnaires and spirometry at baseline (drug commencement), 1, 2, 3 (drug cessation) and 4 months (1 month after drug cessation). There was no significant difference in the baseline demographic characteristics between the treatment and the control groups in age, gender, time from HSCT to BOS, time since diagnosis of BOS, chronic GVHD, baseline respiratory symptom scores and baseline forced expiratory volume in 1 s (FEV(1)). Throughout and after 3 months of treatment, there were no significant changes in respiratory symptom scores and FEV(1) measurements between the treatment and the control groups. In conclusion, there was no significant benefit of 3 months of oral azithromycin on the respiratory symptoms and lung function in patients with relatively late BOS after HSCT in this randomized placebo-controlled study.
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Antibacterianos/administración & dosificación , Azitromicina/administración & dosificación , Bronquiolitis Obliterante/tratamiento farmacológico , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas , Administración Oral , Adulto , Bronquiolitis Obliterante/etiología , Enfermedad Crónica , Método Doble Ciego , Femenino , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/etiología , Humanos , Masculino , Persona de Mediana Edad , Síndrome , Factores de Tiempo , Trasplante HomólogoRESUMEN
Natural killer (NK) cell lymphomas/leukemias are rare neoplasms with an aggressive clinical behavior. The majority of the cases belong to extranodal NK/T-cell lymphoma, nasal type (ENKTL) in the current WHO classification scheme. Gene-expression profiling (GEP) of 21 ENKTL and NK-cell lymphoma/leukemia patients, 17 NK- and T-cell lines and 5 indolent NK-cell large-granular-lymphocytic proliferation was performed and compared with 125 peripheral T-cell lymphoma (PTCL) patients previously studied. The molecular classifier derived for ENKTL patients was comprised of 84 transcripts with the majority of them contributed by the neoplastic NK cells. The classifier also identified a set of γδ-PTCLs both in the ENKTL cases as well as in cases initially classified as PTCL-not otherwise specified. These γδ-PTCLs expressed transcripts associated with the T-cell receptor (TCR)/CD3 complex, suggesting T cell rather than NK-cell lineage. They were very similar to NK-cell tumors by GEP, but were distinct from cytotoxic (αß)-PTCL and hepatosplenic T-cell lymphoma, indicating derivation from an ontogenically and functionally distinct subset of γδ T cells. They showed distinct expression of Vγ9, Vδ2 transcripts and were positive for TCRγ, but negative for TCRß by immunohistochemistry. Targeted inhibition of two oncogenic pathways (AURKA and NOTCH-1) by small-molecular inhibitors induced significant growth arrest in NK-cell lines, thus providing a rationale for clinical trials of these inhibitors in NK-cell malignancies.
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Células Asesinas Naturales/patología , Linfoma no Hodgkin/patología , Linfoma de Células T Periférico/patología , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Receptores de Antígenos de Linfocitos T gamma-delta , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Aurora Quinasa A , Aurora Quinasas , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de Proteínas Quinasas/farmacología , Receptores Notch/antagonistas & inhibidores , Transducción de Señal , Células Tumorales Cultivadas , Adulto JovenAsunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Sistema Hematopoyético , Agonistas Mieloablativos/uso terapéutico , Regeneración , Adolescente , Adulto , Femenino , Humanos , Linfoma/terapia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Quimera por Trasplante , Trasplante Homólogo , Adulto JovenAsunto(s)
Infecciones por Virus de Epstein-Barr/complicaciones , Herpesvirus Humano 4/genética , Linfoma Extranodal de Células NK-T/complicaciones , ARN Viral/genética , Neoplasias Cutáneas/complicaciones , Carcinoma , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/genética , Humanos , Linfoma Extranodal de Células NK-T/diagnóstico , Linfoma Extranodal de Células NK-T/genética , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/complicaciones , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/genética , Neoplasias Primarias Múltiples/diagnóstico , Neoplasias Primarias Múltiples/genética , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/etiología , Neoplasias Cutáneas/genéticaRESUMEN
The first case of haematopoietic stem cell transplant (HSCT) was performed at the Bone Marrow Transplant Center, Queen Mary Hospital (QMH) in 1990. Since then three more transplant centres have been established: Prince of Wales Hospital (1991) mainly in paediatric transplant, Queen Elizabeth Hospital (1995) and Tuen Mun Hospital (2006) in adult autologous transplant. Up to the end of 2008, a little over 2000 transplants have been performed in Hong Kong, and QMH takes up about 85% of the total number of cases. A unified HSCT registry in Hong Kong is desirable and is yet to be established. At QMH, by the end of 2008, a total of 1708 transplant procedures have been performed with 83% (1417) being first-time transplants and the rest (291, 17%) are repeat transplants mostly for relapsed patients. The numbers of male and female patients are 955 and 753, respectively. The median age is 35.4 years (range, 3 months to 67 years) with 85.8% of the transplants performed in adults (> 18 years). The type of donor includes 34% autologous, 1% syngeneic, 38% related allogeneic and 27% unrelated allogeneic. The top five indications of the first-time transplants are acute myeloid leukaemia (25.8%), chronic myeloid leukaemia (15.9%), lymphoma (14.6%), acute lymphoblastic leukaemia (14.5%), and myeloma (8.6%). With the development of peripheral blood stem cell collection, in recent years it is performed in 50% of the allogeneic and 80% of the autologous cases. Bone marrow harvest in autologous cases is only for patients who fail peripheral blood stem cell mobilisation. Transplant outcomes are reported to the Center for International Blood and Marrow Transplant Research and long-term survivals are in general comparable to international standard.
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Trasplante de Células Madre Hematopoyéticas/tendencias , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Trasplante de Células Madre Hematopoyéticas/etnología , Trasplante de Células Madre Hematopoyéticas/estadística & datos numéricos , Hong Kong/epidemiología , Humanos , Incidencia , Lactante , Leucemia/terapia , Linfoma no Hodgkin/terapia , Masculino , Persona de Mediana Edad , Trasplante de Células Madre de Sangre Periférica/estadística & datos numéricos , Trasplante de Células Madre de Sangre Periférica/tendencias , Trasplante Homólogo/tendencias , Adulto JovenRESUMEN
Deficiency in glucose-6-phosphate dehydrogenase (G6PD), an X-linked recessive red cell enzymopathy, is endemic in Southern Chinese. Universal screening of newborn is done in Hong Kong, Taiwan and Singapore, among other places. In Hong Kong, 4.8% of males are affected and seven common G6PD alleles account for over 99% of all defects. Male hemizygotes suffer from severe deficiency, while female heterozygotes may also be affected. Deficiency of G6PD may affect haematopoietic stem cell transplantation (HSCT) recipients and donors, before and after HSCT. Female patients with clonal erythropoiesis (eg myelodysplasia/myeloproliferative diseases) will have the male population incidence of G6PD. Quantitative enzyme level screening is prudent for donors and recipients, and should be repeated after engraftment. Cotrimoxazole prophylaxis should be avoided in known male and female carriers, including those with low-normal G6PD enzyme levels. Our experience suggested that G6PD-deficient marrow, stem cell and cord blood donor units have no engraftment problems. Post-engraftment G6PD levels correlate with those in donors. An acquired change in G6PD status may serve as a surrogate marker for engraftment. For female heterozygote donors with normal G6PD levels, skewing of lyonized X-chromosome ratio during engraftment may result in over-expression of the deficient allele. This can result in unexpected significant G6PD deficiency. Hence, a repeat G6PD screening at stable engraftment is recommended, especially before commencement of oxidative medications.
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Deficiencia de Glucosafosfato Deshidrogenasa/etnología , Trasplante de Células Madre Hematopoyéticas/etnología , Células Madre Hematopoyéticas/enzimología , China/epidemiología , Selección de Donante , Femenino , Deficiencia de Glucosafosfato Deshidrogenasa/genética , Humanos , Masculino , Polimorfismo de Nucleótido Simple/genética , PrevalenciaRESUMEN
Natural killer (NK)-cell malignancies are among the most aggressive lymphoid neoplasms with very poor prognosis. We performed array comparative genomic hybridization analysis on a number of NK cell lines and primary tumors to gain better understanding of the pathogenesis and tumor biology of these malignancies. We also obtained transcriptional profiles of genes residing in these regions and compared them with normal and activated NK cells. Only 30-50% of the genes residing in the gained or deleted regions showed corresponding increased or decreased expression. However, many of the upregulated genes in regions of gain are functionally important for the proliferation and growth of the neoplastic population. Genes downregulated in regions of loss included many transcription factors or repressors, tumor suppressors or negative regulators of the cell cycle. The minimal common region of deletion in 6q21 included three known genes (PRDM1, ATG5 and AIM1) showing generally low expression. Mutations resulting in truncated PRDM1 and changes in conserved amino-acid sequences of AIM1 were detected. Highly methylated CpG islands 5' of PRDM1 and AIM1 correlated with low expression of the transcripts. Reversal of methylation by Decitabine induced expression of PRDM1 and cell death. In conclusion, we have shown a general tumor-promoting effect of genetic alterations and have identified PRDM1 as the most likely target gene in del6q21. ATG5, an essential gene for autophagy and AIM1, a gene implicated in melanoma, may also participate in the functional abnormalities.
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Hibridación Genómica Comparativa , Cristalinas/genética , Regulación Neoplásica de la Expresión Génica , Genes Supresores de Tumor , Células Asesinas Naturales/patología , Linfoma/genética , Proteínas de la Membrana/genética , Proteínas Asociadas a Microtúbulos/genética , Proteínas Represoras/genética , Adulto , Anciano , Proteína 5 Relacionada con la Autofagia , Proliferación Celular , Cromosomas Humanos Par 6 , Perfilación de la Expresión Génica , Humanos , Linfoma/patología , Persona de Mediana Edad , Factor 1 de Unión al Dominio 1 de Regulación Positiva , Células Tumorales CultivadasRESUMEN
We performed MRI assessment in 37 adult Chinese patients with thalassemia intermedia and hemoglobin H disease. Despite abnormal ferritin and liver T2*, only 5% of patients had cardiac hemosiderosis. The two patients with reduced ejection fraction had normal cardiac T2*. Half of the cases showed pituitary and pancreatic iron loading. Subclinical endocrine abnormalities (HOMA, insulin growth factor) showed correlation with pancreatic, pituitary, and cardiac MRI values. Prospective data with serial functional and imaging monitoring is needed to verify the utility for chelation to improve cardiac and endocrine function in this group of patients.
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Hemosiderosis/etiología , Talasemia alfa/complicaciones , Talasemia beta/complicaciones , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , China , Sistema Endocrino/fisiopatología , Femenino , Corazón/fisiología , Humanos , Hígado/patología , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Especificidad de Órganos , Páncreas/patología , Hipófisis/patología , Adulto JovenAsunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical , Deficiencia de Glucosafosfato Deshidrogenasa/genética , Supervivencia de Injerto , Leucemia Mieloide Aguda/terapia , Quimera por Trasplante/genética , Acondicionamiento Pretrasplante , Humanos , Leucemia Mieloide Aguda/genética , Masculino , Persona de Mediana EdadAsunto(s)
Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Antineoplásicos/administración & dosificación , Citomegalovirus/efectos de los fármacos , Ganciclovir/análogos & derivados , Alemtuzumab , Anticuerpos Monoclonales Humanizados , Evaluación de Medicamentos , Ganciclovir/administración & dosificación , Humanos , Premedicación , Valganciclovir , Activación Viral/efectos de los fármacosRESUMEN
PURPOSE: To assess the feasibility of one-stop evaluation of iron load of myocardium, liver, and anterior pituitary gland in thalassemia patients. MATERIALS AND METHODS: Fifty thalassemia major patients underwent a breath-hold magnetic resonance imaging (MRI) sequence for assessment of T2* for liver and myocardium, a short axis cine trueFISP sequence covering base to apex to assess the ejection fraction of left ventricle, and a turbo spin echo T2-weighted sequence for the anterior pituitary gland. The MRI parameters were correlated with serum growth hormone, insulin growth factor-1 (IGF-1), insulin growth factor binding protein-3 (IGFBP-3), and endocrine failure. RESULTS: Ferritin was found to be associated with T2* liver (P < 0.005), T2SI (signal intensity) pituitary (P = 0.001), and T2 pituitary/fat (P = 0.001), but not with T2* heart. There was significant correlation of T2SI pituitary with IGF-1 and IGFBP-3. T2* liver (P < 0.001), T2* heart (P < 0.001), pituitary SI (P < 0.001) and pituitary/fat SI (P = 0.002) were also found to be significantly correlated with a history of hypogonadism. T2* heart was also found to be significantly correlated with IGF-1. CONCLUSION: A quick MRI protocol for assessment of T2* liver, T2* heart, and T2SI pituitary is technically feasible. This might form an objective basis to monitor the response to different organs to chelation therapy.
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Hierro/análisis , Hígado/química , Imagen por Resonancia Magnética , Miocardio/química , Adenohipófisis/química , Talasemia/metabolismo , Adolescente , Adulto , Niño , Estudios de Factibilidad , Femenino , Humanos , MasculinoAsunto(s)
Predisposición Genética a la Enfermedad , Linfoma de Células B/complicaciones , Linfoma de Células B/genética , Trastornos Mieloproliferativos/complicaciones , Trastornos Mieloproliferativos/genética , Anciano , Humanos , Linfoma de Células B/patología , Masculino , Trastornos Mieloproliferativos/patologíaRESUMEN
Graft-versus-host disease (GVHD) often complicates allogeneic stem cell transplantation (SCT) and affects mainly the gut, liver, lung and skin. The microscopic morphological features of late-phase sclerodermatous chronic GVHD in the skin, namely epidermal atrophy, lymphoplasmacytic infiltration, dense dermal fibrosis and adnexal atrophy, are histologically indistinguishable from those in sporadic systemic sclerosis, morphoea and the related condition of lichen sclerosus. Mucosal orifices including those of the genitourinary system may be severely affected. We present three SCT recipients with chronic GVHD and severe posthitis leading to phimosis requiring surgery. The excised prepuces showed features of lichen sclerosus including epidermal atrophy and a subepidermal zone of eosinophilic, homogeneous and hyalinized collagen above a band-like lymphoplasmacytic infiltrate. These cases add further evidence to support the notion that penile lichen sclerosus should be included within the expanding sclerodermoid spectrum of late-stage cutaneous chronic GVHD.