[Clinical study of anti-human T cell porcine immunoglobulin with recombinant human tumor necrosis factor-α receptor II: IgG Fc in the treatment of 35 cases of grade III/IV acute graft-versus-host disease after allo-HSCT].

Objective: To evaluate the efficacy and safety of anti-human T lymphocyte porcine immunoglobulin (P-ATG) with recombinant human tumor necrosis factor-α receptor Ⅱ:IgG Fc fusion protein (rhTNFR∶Fc, Etanercept) on grade Ⅲ/Ⅳ acute graft-versus-host disease (aGVHD) after allogenic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Thirty-five patients with Grade Ⅲ/Ⅳ aGVHD who received P-ATG with etanercept therapy after allo-HSCT were retrospectively analyzed. P-ATGs (5 mg·kg(-1)·d(-1)) were administrated for 3 to 5 days, and then 5mg/kg was sequentially administrated, QOD to BIW. Etanercepts were administrated 25 mg, twice a week (12.5 mg, BIW for pediatric patients) . Results: Among the 35 patients with grade Ⅲ/Ⅳ aGVHD, 21 were males and 14 females, with a median age of 10 (3-54) years. A total of 19 cases of acute myeloid leukemia, 13 of acute lymphoblastic leukemia, 1 of severe aplastic anemia, 1 of myelodysplastic syndrome, and 1 of mixed phenotypic acute leukemia were noted. The overall response (OR) rate of P-ATG with etanercept was 85.7% (30/35) , with complete response (CR) and partial response (PR) rates of 34.3% (12/35) and 51.4% (18/35) , respectively, on day 28. The OR rate of grade Ⅲ aGVHD group was higher than of grade IV aGVHD group [100% (19/19) vs. 68.8% (11/16) , P=0.004]. On day 56, the OR rate became 77.2% (27/35) , with CR and PR rates of 62.9% (22/35) and 14.3% (5/35) , respectively. The OR rate of grade Ⅲ aGVHD group was also higher than of grade Ⅳ aGVHD group [89.5% (17/19) vs. 62.5% (10/16) , P=0.009]. Thirty-five patients had no adverse effects such as fever, chills, and rash during the P-ATG infusion, and no obvious liver and kidney function damage was observed after treatment. The main treatment-related complication was infection. The reactivation rates of CMV and EBV were 77.1% (27/35) and 22.9% (8/35) , respectively, and the bacterial infection rate was 48.6% (17/35) . With a median follow-up time of 13 (1-55) months after HSCT, the 1-year and 2-year OS rates were (68.1±8.0) % and (64.3±8.4) % , respectively. The 1-year OS rate of grade Ⅲ aGVHD group was superior to grade Ⅳ aGVHD group [ (84.2±8.4) % vs. (47.6±13.1) % , χ(2)=3.38, P=0.05]. Conclusion: This study demonstrated that P-ATG with etanercept was effective and safe in treating grade Ⅲ-Ⅳ aGVHD after allo-HSCT.

CD200 is a useful diagnostic marker for identifying atypical chronic lymphocytic leukemia by flow cytometry.

INTRODUCTION: Immunophenotyping by flow cytometry is routinely employed in distinguishing between chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). Inclusion of CD200 has been reported to contribute to more reliable differentiation between CLL and MCL. We investigated the value of CD200 in assessment of atypical CLL cases. METHODS: CD200 expression on mature B cell neoplasms was studied by eight-color flow cytometry in combination with a conventional panel of flow cytometry markers. The study included 70 control samples, 63 samples with CLL or atypical CLL phenotype, 6 MCL samples, and 40 samples of other mature B cell neoplasms. RESULTS: All CLL samples were positive for CD200, whereas MCL samples were dim or negative for CD200. Of the CLL samples, 7 were atypical by conventional flow cytometry, with Matutes scores ≤3. These cases were tested for evidence of a t(11;14) translocation, characteristic of MCL, and all were negative, consistent with their classification as atypical CLL. All these atypical CLL samples were strongly positive for CD200. CONCLUSION: CD200 proved to be a useful marker for differentiation between CLL and MCL by flow cytometry. In particular, CD200 was useful in distinguishing CLL samples with atypical immunophenotypes from MCL.

LncRNA HOTAIR contributes to the tumorigenesis of nasopharyngeal carcinoma via up-regulating FASN.

OBJECTIVE: The therapeutic options for nasopharyngeal carcinoma (NPC) treatment have been restricted mainly to radiotherapy or chemotherapy, and the clinical treatment effect remains unsatisfactory. The primary purpose of this study was to investigate the molecular mechanisms of NPC and to find effective novel therapeutic targets for NPC. PATIENTS AND METHODS: In order to analyze the expression level of lncRNA HOTAIR and FASN in human NPC clinical tissues or NPC cells, total RNA was extracted with TRIzol and the relative mRNA expression levels were detected by quantitative Real-time PCR. The endogenous expression of HOTAIR was modulated using lentivirus vectors transfection. The protein levels of Fatty acid synthase (FASN), p21 and MMP-9 in NPC cells were determined by Western blot when HOTAIR was knockdown. A free Fatty acid quantitation assay was performed to detect the intracellular free Fatty acid in NPC cells. The CCK-8 and colony formation assays were performed for cell viability and proliferation determination. The cell cycle of NPC cells was also determined by flow cytometric analysis. A matrigel invasion assay was performed to analyze the invasive ability of NPC cells. RESULTS: In this study, we observed a significant upregulation of lncRNA HOTAIR in NPC cells and clinical NPC specimens. The expression of Fatty acid synthase (FASN) was positively correlated to HOTAIR in NPC specimens. Knockdown of HOTAIR led to downregulation of FASN in NPC cells, thus suppressing cell proliferation and invasion. Additionally, de novo synthesis of cellular free fatty acid in NPC cells was inhibited when HOTAIR was knockdown. Furthermore, the protein levels of MMP-9 and p21 were downregulated when HOTAIR was knockdown. CONCLUSIONS: We suggest that HOTAIR is important in the progression and recurrence of NPC, perhaps through upregulating FASN. Targeting HOTAIR may be an effective therapeutic strategy for NPC.

Detergent Sclerosants Stimulate Leukocyte Apoptosis and Oncosis.

OBJECTIVE/BACKGROUND: The objective was to investigate the effects of the detergent sclerosants sodium tetradecyl sulfate (STS) and polidocanol (POL) on human leukocytes at sublytic concentrations. METHODS: Leukocytes were isolated and labelled with antibodies to assess for apoptosis and examined with confocal microscopy and flow cytometry. Isolated leukocyte count and viability was assessed using trypan blue, and propidium iodide staining. Phosphatidylserine (PS) exposure, a universal hallmark to measure cell apoptosis, was identified by flow cytometry using lactadherin. Caspases 3, 8, and 9, and Bax activation, as well as inhibitory assays with pan-caspase (Z-VAD-FMK) and Bax (BI-6C9) were assessed to determine apoptotic pathways. Porimin activation was used to assess cell permeability. RESULTS: Up to 40% of leukocytes maintained membrane integrity at sublytic concentrations (≤0.15%) of sclerosants. The remaining 60% did not maintain membrane integrity but were not completely lysed. PS exposure was increased with both STS and POL exhibiting a dose- and time-dependant trend. While activation of caspases 3, 8, and 9, as well as Bax activation, were increased in leukocytes stimulated with low concentrations of STS, only caspases 3 and 9 and Bax were increased with POL. Inhibitory assays demonstrated caspases 3, 8, and 9, and Bax inhibition at low concentrations with both STS and POL. Both agents increased the leukocyte activation of porimin at all concentrations. On confocal microscopy, stains for caspases 3, 8, and 9, and Bax were increased for both STS and POL. Porimin stain was markedly positive for both STS and POL. CONCLUSION: Both sclerosants induced leukocyte apoptosis at sublytic concentrations. STS activated both extrinsic and intrinsic pathways of apoptosis, while POL stimulated the intrinsic pathway of apoptosis only. Both agents induced oncosis. Based on these results, STS appears to have a greater effect than POL.

Primary central nervous system posttransplantation lymphoproliferative disorder after heart and lung transplantation.

Primary central nervous system posttransplantation lymphoproliferative disorder (PCNS-PTLD) is uncommon, especially after heart or lung transplantation. Database analysis from a single heart and lung transplantation centre and a literature review pertaining to PCNS-PTLD was performed. In this study, the prevalence of PCNS-PTLD was 0.18% after heart and/or lung transplants. Of 1674 transplants, three cases of PCNS-PTLD developed 14 months, 9 years and 17 years posttransplant, and all were Epstein-Barr virus driven malignancies. Literature review of the topic revealed predominantly retrospective studies, with most reported cases after renal transplantation. The overall survival is poor, and it may be improved by early diagnosis and treatment. There are no published guidelines on the management of PCNS-PTLD; immune-chemotherapy in conjunction with reduction of immune suppression is preferred based on available evidence.

Detergent sclerosants are deactivated and consumed by circulating blood cells.

OBJECTIVE: To investigate the deactivating effects of circulating blood cells on the lytic activity of detergent sclerosants. METHODS: Samples of whole blood (WB), platelet-rich plasma (PRP), and isolated leukocytes were incubated with various concentrations of sodium tetradecyl sulfate (STS) or polidocanol (POL) and added to human umbilical vein endothelial cells (HUVECs), which were then counted using a fluorescent plate reader. Full blood counting was performed using a hematology analyzer. Platelet lysis and microparticle formation was assessed using lactadherin binding in flow cytometry. RESULTS: Detergent sclerosant activity was decreased in WB when compared with plasma and saline controls. The sclerosant lytic activity on endothelial cells was increased 23-fold for STS and 59-fold for POL in saline controls compared with WB. At high concentrations, sclerosants lysed erythrocytes, leukocytes, and platelets. Platelets were more sensitive to the lytic activity of sclerosants than other cell types. Neutrophils were the most susceptible of all leukocytes to the lytic activity of sclerosants. The presence of erythrocytes and leukocytes in samples decreased the lytic activity of sclerosants. Sclerosants at all concentrations induced erythrocyte-derived microparticle formation. CONCLUSIONS: Detergent sclerosants are consumed and deactivated by circulating blood cells. This deactivating effect is above and beyond the neutralizing effects of plasma proteins and contributes to the overall neutralizing effect of blood. Different blood cell types exhibited varying levels of vulnerability to the lytic activity of sclerosants with platelets being the most and erythrocytes the least vulnerable (platelets > leukocytes > erythrocytes).

Essential, but at what risk? A prospective study on central venous access in patients with haematological malignancies.

AIMS: Central venous catheters (CVC) are integral to modern haematology practice; however, they are associated with a range of complications. This prospective study aimed to determine the rate of CVC-related complications and risk factors in haematology patients, who are vulnerable because of their underlying pathology and treatments. METHODS: All inpatients that had a non-tunnelled CVC inserted in a 14-month period in the haematology ward at St Vincent's Hospital were enrolled. Complications (immediate and late), demographics, type of device, insertion technique and duration of dwell, were examined using multivariate analysis. RESULTS: One hundred and seventy-four CVC in 84 patients were recorded, representing 3016 catheter-days. At least one complication was found in 43 (24.7%) patients. Immediate complications occurred in 13 (7.5%) insertions, with a higher rate in those inserted after ≥2 attempts compared with one (P = 0.02). Catheter-related bloodstream infection occurred at a rate of 7.6 per 1000 catheter-days, with acute lymphoblastic leukaemia associated with a higher rate (P = 0.02), and subclavian vein CVC had a lower rate compared with other locations (P < 0.01). Thrombosis was found in seven (4.0%) patients, with subclavian CVC carrying an increased risk (P = 0.02). CONCLUSIONS: This prospective observational study found almost a quarter of haematology patients experience a CVC-related complication. An association was found with a number of attempts at insertion and immediate complications; other risk factors included anatomical location, underlying disease and duration of catheterisation. The relatively high complication rate, compared with reports of non-haematology patients, highlights the need to improve CVC management, a vital part of care for this population.

Increased activity and improved outcome in unrelated donor haemopoietic cell transplants for acute myeloid leukaemia in Australia, 1992-2005.

BACKGROUND/AIM: Numbers of unrelated donor allogeneic haemopoietic cell transplants (HCT) for acute myeloid leukaemia have increased in Australia in recent years. The aims of this study were to investigate the components of this change and find contributing factors to changes in outcome. METHODS: The study method was a retrospective analysis of 213 consecutive first unrelated donor HCT for acute myeloid leukaemia performed within Australia for adult patients during the years of 1992-1997 (n= 43) and 1998-2005 (n= 170). RESULTS: The proportion of patients transplanted in first or second complete remission (CR) increased markedly from 21% in 1992-1997 to 52% in 1998-2005. The cumulative incidence of relapse at 1 year post HCT was significantly lower for the later cohort (22% vs 30%, P= 0.04) and for patients transplanted in CR compared with those not in CR (16% vs 31%, P= 0.01). The overall survival probability was significantly better at 5 years post HCT for patients transplanted in 1998-2005 compared with 1992-1997 (40% vs 21%, P= 0.04). Multivariate analysis identified five independent significant favourable factors for survival among the whole patient group: age under 40 years, transplant in CR1, CR2 or first relapse, patient CMV seronegativity, good performance status and year of transplant within 1998-2005. CONCLUSION: The later cohort of patients had improved survival even after allowing for the effects of age, remission status and other factors, which suggests a general improvement in the safety of the procedure over time, particularly for patients in early disease stages at transplant.

In vitro effects of detergent sclerosants on clot formation and fibrinolysis.

OBJECTIVE: To investigate the in vitro effects of detergent sclerosants sodium tetradecyl sulphate (STS) and polidocanol (POL) on clot formation and lysis. MATERIALS AND METHODS: clot kinetics were assessed in whole blood by thromboelastography (TEG®) and rotational thromboelastometry (ROTEM®). Fibrinogen was measured by the Clauss method in plasma and factor XIII (FXIII) by enzyme-linked immunosorbent assay (ELISA). Turbidity measurements were used to assess clot lysis in plasma, and fibrinolysis in non-cross-linked and cross-linked fibrin. D-dimer was measured by VIDAS®, STA®Liatest® and AxSYM® assays. RESULTS: Strong clots were formed at low sclerosant concentrations (0.075-0.1%). At midrange concentrations (0.15% STS, 0.15-0.3% POL), both agents inhibited the contribution of platelets to clot firmness and formed weak clots prone to lysis. At higher concentrations (STS ≥ 0.3% and POL ≥ 0.6%), clot formation was inhibited. STS destroyed FXIII at ≥ 0.15% and fibrinogen at ≥ 0.6%. Neither sclerosant had a significant effect on cross-linked fibrin, but STS had a lytic effect on non-cross-linked fibrin. STS caused an artefactual elevation of D-dimer in the VIDAS® assay when fibrinogen was present. CONCLUSION: Detergent sclerosants demonstrated a trimodal effect on clot formation, initiating strong clots at low concentrations, weak clots at midrange concentrations and preventing clot formation at higher concentrations. Neither agent had fibrinolytic activity.

Polyphyllin D exerts potent anti-tumour effects on Lewis cancer cells under hypoxic conditions.

Paris polyphylla has been used to treat cancer in China for many years and components of the plant, such as polyphyllin D, may have potent antiproliferative effects in vitro. To investigate the potential antitumour effects of polyphyllin D on cancer cells under hypoxia, Lewis lung cancer cells and mouse tracheal epithelial cells were cultured with or without polyphyllin D under normoxic and hypoxic conditions. Proliferation and apoptosis of cells were assayed. Real-time reverse transcription-polymerase chain reaction was used to quantify the expression of hypoxia-inducible factor 1 alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) mRNA. Polyphyllin D decreased cell proliferation, increased apoptosis and inhibited expression of HIF-1alpha and VEGF mRNAs in Lewis cells. These effects were greater under hypoxic than normoxic conditions. Polyphyllin D did not show a cytotoxic effect in non-tumour cells (mouse skin fibroblasts and tracheal epithelial cells). These results suggest that polyphyllin D potentially has anticancer effects in vitro under hypoxia.

The lytic effects of detergent sclerosants on erythrocytes, platelets, endothelial cells and microparticles are attenuated by albumin and other plasma components in vitro.

OBJECTIVE: To investigate the lytic effects of sodium tetradecyl sulphate (STS) and polidocanol (POL) on erythrocytes, platelets, endothelial cells and platelet-derived microparticle (PDMP) formation in vitro and the potential protective effects of serum albumin and agents such as procaine. MATERIALS AND METHODS: The effects of sclerosants were studied in blood samples obtained from normal individuals. Absorbance densitometry was used to assess the lytic effects of sclerosants on blood cells and cultured human microvascular endothelial cells (HMEC) in plasma and in saline. PDMP were quantified by flow cytometry. RESULTS: Haemolysis occurred in whole blood at sclerosant concentrations greater than 0.25% for STS and above 0.45% for POL. Similar concentrations of both agents caused platelet and endothelial cell lysis. Both sclerosants released PDMP at low concentrations but destroyed PDMP at higher concentrations. Albumin significantly reduced the lytic effect of both sclerosants on all cells but had a greater inhibitory effect on POL. Protamine at 0.01% had a neutralising effect on STS, whereas procaine and lignocaine showed no such activity. CONCLUSIONS: Sclerosants at therapeutic concentrations lyse blood cells and endothelial cells in vitro. This effect is strongly reduced by serum albumin possibly contributing towards the low incidence of thromboembolic complications of sclerotherapy.

In vitro effects of detergent sclerosants on coagulation, platelets and microparticles.

OBJECTIVES: To investigate the in vitro effects of Sodium Tetradecyl Sulphate (STS) and Polidocanol (POL) on clotting tests, clotting factors, platelets and microparticles. MATERIALS AND METHODS: Platelet rich (PRP) and platelet poor (PPP) plasmas were incubated with varying concentrations of STS and POL. Clotting tests, platelet/plasma turbidity, and microparticle studies were performed. Specimens were mixed with individual factor deficient plasmas and clotting factor activities were studied. RESULTS: STS at high concentrations (>0.3%) destroyed platelets, microparticles and the clotting factors V, VII and X. It prolonged all clotting tests including prothrombin time (PT), activated partial thromboplastin time (APTT), non-activated partial thromboplastin time (NAPTT), thrombin time (TT), factor Xa clotting time (XACT) and surface activated clotting time (SACT). Higher concentrations of POL were required to achieve some anticoagulant activity. Low sclerosant concentrations shortened XACT and SACT, and induced release of procoagulant platelet derived microparticles. Increased exposure time resulted in increased procoagulant activity. STS at concentrations higher than 0.5% precipitated a complex containing apolipoprotein b and fibrinogen. CONCLUSIONS: Detergent sclerosants affect the clotting mechanism by interfering with clotting factor activities, procoagulant phospholipids and platelet derived microparticles. STS has more anticoagulant activity than POL in high concentrations. Low concentration sclerosants demonstrate procoagulant activity.

Australasian CD34+ quality assurance program and rationale for the clinical utility of the single-platform method for CD34+ cell enumeration.

BACKGROUND: Enumeration of CD34(+) cells should be accurate and comparable between institutions, particularly when making clinical decisions, evaluating data, and in clinical trials. An Australasian CD34(+) quality assurance program (QAP) has been established to compare CD34(+) cell results and method (Part 1). Unexpected variation in WBCCs led to Part 2 of this report. METHODS: Part 1: Methods reagents and results were evaluated for 12 QAP samples analyzed by 36-43 centers. Part 2: The effects of different anticoagulants on WBCC of 12 peripheral blood samples (PBs) were compared using three cell counters. To test the validity of applying the conclusions to clinical samples, the WBCCs of leukapheresed products and BM harvest were also compared. RESULTS: Part 1: In some samples, WBCCs determined by certain cell-counter groups were significantly different. Results for percentage of CD34(+) and CD34(+)/microL suggest that standardization on the lyse-no-wash and single platform (SP) method reduces variation of results between institutions. Part 2: Using different counters, PB WBCC in ACD-A showed greater variation than the same PB in EDTA. For PB in different anticoagulants, the extent of difference in WBCC for the same PB is dependent on the counter used. DISCUSSION: This CD34 QAP has identified ACD-A as an additional factor that contributes to the disparate WBCCs, which may further compromise the accuracy of CD34(+) cell counts obtained by the dual platform (DP) method, especially for leukapheresed products. In order to achieve greater accuracy within individual institutions, as well as permitting more reliable inter-institutional comparisons, our data supports the adoption of the SP as the standard method for CD34(+) cell enumeration.

Successful peripheral blood stem cell mobilisation with filgrastim in patients with chronic myeloid leukaemia achieving complete cytogenetic response with imatinib, without increasing disease burden as measured by quantitative real-time PCR.

Imatinib mesylate (Glivec) is a selective inhibitor of bcr-abl tyrosine kinase, the product of the Philadelphia chromosome, which is the hallmark of chronic myeloid leukaemia (CML). With imatinib, complete cytogenetic response (CCR) can be achieved in over 70% of newly diagnosed patients with CML. However, the optimal long-term management of patients who achieve CCR after imatinib is unknown. With longer follow-up, it is anticipated that some patients are likely to progress and become candidates for autologous transplantation. We studied filgrastim (r-metHuG-CSF) mobilisation of peripheral blood stem cells (PBSC) in 32 patients who have achieved CCR with imatinib. Our data demonstrate that (1) the target CD34(+) cell yields of >/=2.0 x 10(6)/kg were attained with filgrastim 10 microg/kg/day, in 9/18 (50%) of patients during uninterrupted imatinib therapy, and in 10/14 (70%) when imatinib was temporarily withheld. The median CD34(+) cell yield per aphaeresis was 0.70 x 10(6)/kg (range 0.14-2.18) and 2.90 x 10(6)/kg (range 0.15-8.71) in the two groups, respectively (P&<0.005). (2) The cell yields did not correlate with the duration of imatinib administration. (3) There was no impact of the mobilisation procedure on the level of leukaemia as measured by serial blood bcr-abl levels using real-time quantitative PCR with either protocol. (4) bcr-abl remained detectable at low levels in the harvests in most but not all patients. In conclusion, filgrastim can safely be used to mobilise PBSC in patients who have achieved CCR with imatinib, but CD34(+) cell yields are significantly improved when imatinib is temporarily withheld.

Patterns of failure with increasing intensification of induction chemotherapy for acute myeloid leukaemia.

Patterns of failure were studied in two consecutive randomized trials of intensified induction therapy carried out by the Australian Leukaemia Study Group (ALSG) between 1984 and 1991 to determine the impact of dose intensification. Patients received standard dose cytarabine and daunorubicin (7-3), 7-3 plus etoposide (7-3-7) or 7-3 plus high-dose cytarabine (HIDAC-3-7) chemotherapy. Patients with FAB M3 morphology were excluded. Time to failure (TTF) was defined as the time from randomization to induction death or removal from study for non-responders, or to relapse or death in complete response (CR) for complete responders. An estimated 86% of 470 de novo patients with acute myeloid leukaemia failed within 10 years of randomization, as a result of death in induction in 17% of the randomized patients, failure to achieve CR in a further 17%, relapse in 44% and death in CR in 8% of patients. An estimated 66% of patients failed as a result of refractory disease or relapse within that period (disease-related failures). Multifactor analysis identified age and peripheral blast count as the most significant pretreatment factors associated with overall TTF. These factors, together with cytogenetics, were significantly associated with disease-related failures. High-dose cytarabine in induction significantly decreased the disease-related failure rate as did allogeneic transplantation in first CR. The impact of high-dose cytarabine did not depend on the cytogenetic risk group.

Synthetic oligonucleotides as therapeutics: the coming of age.

Synthetic oligonucleotides (ODNs) are short nucleic acid chains that can act in a sequence specific manner to control gene expression. Significant progress has been made in the development of synthetic ODN therapeutics since the first demonstration of gene inhibition by antisense ODNs in a cell culture system two decades ago. This new class of therapeutic agents can potentially target any abnormally expressed genes in a broad range of diseases from viral infections to psychoneurological disorders. A number of "first" generation synthetic ODNs have entered into human clinical trials in the last few years. The eminent approval of the first ODN for the treatment of cytomaglovirus retinitis by the FDA in USA will provide much excitement that this new class of compounds holds great promise as a therapeutic "magic bullet". However, many obstacles still exist in the development of this technology. In this review, the current status of synthetic ODN chemistry, drug delivery methods, mechanisms of ODN action, potential clinical applications and its limitations in a wide range of human disorders will be described.

Acral keratotic graft versus host disease simulating warts.

A 55-year-old man experienced persistent oral graft versus host disease after receiving an HLA-matched allogeneic stem cell peripheral blood transplant for chronic myeloid leukaemia. Twelve months post-transplant, multiple keratotic lesions resembling warts developed on his fingers, on his palms and on the soles of his feet. Skin biopsy showed a lichenoid reaction under a hyperplastic and hyperkeratotic epidermis lacking signs of papillomavirus infection. The lesions partially regressed when the patient's oral prednisone was increased. This instance of acral keratotic lesions may represent an unusual expression of chronic graft versus host disease; however, the the hydroxychloroquine which had been used for 8 months to control the patient's oral graft versus host disease cannot be excluded as a cofactor.