Decreased Flow Velocity with Transcranial Color-Coded Duplex Sonography Correlates with Delayed Cerebral Ischemia due to Peripheral Vasospasm of the Middle Cerebral Artery.

BACKGROUND AND OBJECTIVE: Despite intensive therapy, vasospasm remains a major cause of delayed cerebral ischemia (DCI) in worsening patient outcome after aneurysmal subarachnoid hemorrhage (aSAH). Transcranial Doppler (TCD) and transcranial color-coded duplex sonography (TCCS) are noninvasive modalities that can be used to assess vasospasm. However, high flow velocity does not always reflect DCI. The purpose of this study was to investigate the utility of TCD/TCCS in decreasing permanent neurological deficits. METHODS: We retrospectively enrolled patients with aSAH who were treated within 72 hours after onset. TCCS was performed every day from days 4 to 14. Peak systolic velocity (PSV), mean velocity (MV), and pulsatility index were recorded and compared between DCI and non-DCI patients. In patients with DCI, endovascular therapy was administered to improve vasospasm, which led to a documented change in velocity. RESULTS: Of the 73 patients, 7 (9.6%) exhibited DCI. In 5 of the 7 patients, DCI was caused by vasospasm of M2 or the more peripheral middle cerebral artery (MCA), and the PSV and MV of the DCI group were lower than those of the non-DCI group after day 7. Intra-arterial vasodilator therapy (IAVT) was performed for all patients with DCI immediately to increase the flow volume by the next day. CONCLUSIONS: Increasing flow velocity cannot always reveal vasospasm excluding M1. In patients with vasospasm of M2 or more distal arteries, decreasing flow velocity might be suggestive of DCI. IAVT led to increases in the flow velocity through expansion of the peripheral MCA.

Cranioplasty and Duraplasty with Transcranial Color-Coded Duplex Sonography after Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Transcranial color-coded duplex sonography (TCCS) is a noninvasive technique for monitoring of cerebral vasospasm after neurosurgery for aneurismal subarachnoid hemorrhage. In this surgery, surgical materials are used. The goal of the study was to identify materials that can be used with ultrasound and to propose methods for cranioplasty and duraplasty using materials that permit TCCS. METHODS: The chosen neurosurgical materials were titanium mesh plate (TMP), Gore-tex, SEAMDURA, gelatinous sponge, and oxidized cellulose. B-mode imaging was recorded with the materials placed between urethane resin 10 mm in diameter and the urethane phantom model. TCCS was performed to detect middle cerebral artery flow through TMP and Gore-tex. RESULTS: TMP and SEAMDURA permitted penetration of ultrasound in B-mode and Doppler imaging, but the other materials did not do so. CONCLUSIONS: A postcraniotomy window (PCW) on a line extending from the horizontal portion of M1 using only TMP permitted flow imaging with TCCS. In external decompression, TCCS was effective only without use of Gore-tex around the postcraniotomy window. This method allows the middle cerebral artery flow to be detected easily.

Brain abscess associated with patent foramen ovale.

BACKGROUND: Brain abscesses can develop with Tetralogy of Fallot and pulmonary anterior venous fistula with large right-to-left shunt. However, some patients exhibit cryptogenic brain abscess (CBA) in the absence of any such congenital disease or other infections. Patent foramen ovale (PFO) is a very common disease that exhibits right-to-left shunt. This study reports the potential for concern between CBA and PFO. METHODS: We enrolled patients with CBA in our hospital between January 2003 and January 2013. Patients underwent transesophageal echocardiography (TEE) with contrast medium to investigate the presence of PFO. RESULTS: Seven patients were included. Four were females, and the mean age was 67.7 ± 9.2 years. In all patients, TEE failed to reveal any new findings, however, six patients had PFO, and another patient had pulmonary arteriovenous shunt. Four patients had odontopathy. CONCLUSION: In this study, all CBA patients exhibited right-to-left shunt. CBA might be caused by paradoxical embolization of a bacterial mass via PFO. Thus, more patients with CBA need to undergo TEE to detect PFO.

Multiple ischemic strokes caused by nonbacterial thrombotic endocarditis because of gallbladder cancer: a case report.

We report a case of a 62-year-old woman with multiple ischemic strokes caused by nonbacterial thrombotic endocarditis (NBTE) because of gallbladder cancer. Transesophageal echocardiography showed NBTE on the mitral valve. The NBTE disappeared with anticoagulation treatment for 2 weeks. Abdominal computed tomography showed a gallbladder tumor that was surgically resected. Histopathologic studies showed poorly differentiated tumor cells and the production of mucin. Trousseau syndrome with gallbladder cancer is very rare. We suggest that the development of NBTE is related to the production of mucin.

Cerebral hemodynamic benefits after carotid artery stenting in patients with near occlusion.

OBJECTIVE: The natural history and management of patients with near occlusion (NO) of the internal carotid artery are controversial. In particular, it is unclear whether cerebral hemodynamics are compromised in these patients and whether improvement by carotid revascularization leads to the prevention of ischemic stroke. In this study, we measured cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) using single-photon emission computed tomography before and after carotid artery stenting (CAS) for NO to examine the effectiveness of CAS from the perspective of cerebral hemodynamics. METHODS: CAS was performed in 15 patients with NO and in 78 with severe stenosis (≥70%) but without NO at our institution. Resting CBF and CVR to acetazolamide were measured using N-isopropyl-p-[I-123] iodoamphetamine single-photon emission computed tomography before and at 3 to 6 months after CAS. We also measured CBF using the same method for healthy individuals and compared the results among the three groups. RESULTS: CAS was successfully performed in all patients. Before CAS, the mean resting CBF was 26.68 ± 4.23 mL/100 g/min, and the mean CVR was -0.8% ± 15.1% in the patients with NO, both of which were significantly lower than in patients with severe stenosis without NO and in healthy individuals. After CAS, the mean resting CBF and mean CVR in patients with NO increased significantly to 30.07 ± 5.67 mL/100 g/min and 37.0% ± 21.4%, respectively, and there were no significant differences among the three groups. CONCLUSIONS: Before CAS, patients with NO were more hemodynamically compromised than those with severe stenosis without NO. After CAS, significant cerebral hemodynamic improvement and normalization occurred long-term. Thus, from a hemodynamic perspective, CAS was effective in patients with NO.

Effect of early posttransplantation tacrolimus concentration on the development of acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation from unrelated donors.

Only limited data are available regarding the relationship between blood concentration of tacrolimus and its efficacy in preventing acute graft-versus-host disease (aGVHD). We retrospectively evaluated the effects of the whole blood concentration of tacrolimus, which was measured by an automated microparticle enzyme immunoassay, early after allogeneic hematopoietic stem cell transplantation (HSCT) upon the development of aGVHD. Sixty patients, who underwent allogeneic HSCT from serologically human-leukocyte antigen-matched unrelated donors and received continuous infusion of tacrolimus with short-term methotrexate for GVHD prophylaxis, were included in this study. The target range of the blood concentration of tacrolimus was set at 10 to 20 ng/mL, and the level was maintained within this range in all patients. However, the mean blood concentration of tacrolimus during the third week after HSCT was significantly associated with the grades of aGVHD (17.3 ± 2.1 in patients with grades 0-I vs 15.9 ± 2.8 in II-IV and 14.8 ± 2.1 in III-IV; P < .05 and <.01, respectively). Multivariate analysis also demonstrated that higher age (≥35) of donor (odds ratio [OR] = 4.28) and lower mean blood concentrations of tacrolimus during the second (OR = 0.75; 95% confidence interval [CI]: 0.58-0.98) and third weeks (OR = 0.76; 95% CI: 0.58-0.98) after HSCT were significant risk factors for grades II-IV aGVHD (P < .05). We conclude that the early posttransplantation blood concentration of tacrolimus had a significant impact on the development of moderate-to-severe aGVHD after allogeneic HSCT from an unrelated donor.

Safety and efficacy of total body irradiation, cyclophosphamide, and cytarabine as a conditioning regimen for allogeneic hematopoietic stem cell transplantation in patients with acute lymphoblastic leukemia.

Disease relapse still greatly interferes with the success of allogeneic hematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukemia (ALL). This study retrospectively evaluated the long-term safety and efficacy of a conditioning regimen consisting of total body irradiation (TBI; 12 Gy), cyclophosphamide (CY; 60 mg kg(-1) , two doses), and high-dose cytarabine (Ara-C; 2 g m(-2) ; four doses) for patients with ALL. Fifty-five patients (median age: 31-years old) were evaluated. Stem cells were from human leukocyte antigen-identical siblings in 22 patients and from alternative donors in 33. There were no cases of early death before engraftment, and 100-day transplant-related mortality was 7.3%. With a median follow-up period of 9.6 years, 5-year overall and disease-free survival were 63.2% (95% CI: 46.5-79.9%) and 63.6% (95% CI: 47.1-80.1%) in patients with complete remission, respectively, both of which were significantly higher than the values of 27.3% (95% CI: 8.7-46.0%) and 22.7% (95% CI: 5.3-40.1%) for patients in advanced stages (P < 0.01). These results suggest that TBI and CY (TBI-CY) plus Ara-C could be a feasible and effective conditioning regimen for adult patients with ALL both in remission and in advanced stages, and a future study to compare this combination therapy with TBI-CY is required.

Long-term follow-up of reduced-intensity allogeneic hematopoietic stem cell transplantation for refractory or relapsed follicular lymphoma.

Although allogeneic hematopoietic stem cell transplantation (HSCT) is considered the only curative treatment for refractory or relapsed follicular lymphoma (FL), transplant-related mortality (TRM) greatly interferes with the success. A variety of reduced-intensity conditionings (RICs) have been used to reduce TRM, but an optimal conditioning for FL has not been fully established. We retrospectively evaluated the outcome of allogeneic HSCT for FL with RIC consisting of fludarabine and melphalan. Nineteen adult patients with relapsed or refractory FL were conditioned with fludarabine (125 mg/m2) and melphalan (140 mg/m2), and received grafts from an HLA-identical sibling (n = 6) or an unrelated donor (n = 13). For the prophylaxis of graft-versus-host disease (GVHD), cyclosporine A or tacrolimus with short-term methotrexate was given. There were no early deaths before engraftment, and all patients achieved engraftment. Three patients died of extensive-type chronic GVHD (n = 2) or bacterial infection (n = 1) without disease progression. With a median follow-up period of 75.2 months (range: 33.3­111.9 months), 16 patients were alive without disease progression. Both the 5-year overall and progression-free survival rates were 84.2% (95% CI: 67.7­100%). These results strongly suggest that allogeneic HSCT with RIC using fludarabine and melphalan could be a promising treatment choice for refractory or relapsed FL.

Variable magnitude of drug interaction between oral voriconazole and cyclosporine A in recipients of allogeneic hematopoietic stem cell transplantation.

Drug interaction between voriconazole and calcineurin inhibitors is often problematic after allogeneic hematopoietic stem cell transplantation (HSCT) or solid organ transplantation. We previously demonstrated an unpredictable inter-individual variability in the magnitude of this drug interaction; however, the route of drug administration was not taken into account. In this study, the drug interaction between voriconazole and calcineurin inhibitors was further analyzed under the condition that both agents were administered orally. Twenty adult recipients of HSCT who had already been on a steady dose of oral cyclosporine A (CsA) and were started on oral voriconazole (400 mg/d) were eligible. The changes in the concentration/dose (C/D) ratio of CsA were evaluated by comparing the trough concentrations of CsA measured before and 7-10 d after initiating voriconazole. The median C/D ratio of CsA increased significantly from 64.1 to 114.3 (ng/mL)/(mg/kg) after initiating voriconazole (p < 0.01), and the median increase was 83.0% (range, 0.3-224.7%). The plasma concentration of voriconazole did not correlate significantly with the increase of the C/D ratio (ρ = -0.18, p = 0.45). These results indicate that the magnitude of drug interaction between oral voriconazole and CsA is widely variable, and it could not be explained by the difference in the blood levels of voriconazole. Further studies are required to elucidate the mechanism for this variability.

[Marked improvement of anemia during treatment with deferasirox in patients with primary myelofibrosis and acute myeloid leukemia with myelodysplasia-related changes].

We report two patients who achieved a marked improvement of hematopoiesis with the use of deferasirox (DSX) for transfusional iron overload. Case 1 is an 81-year-old male who was diagnosed with primary myelofibrosis in July, 2007. He required regular red blood cell (RBC) transfusion of 4 units/month when he was started on DSX treatment in June, 2009. Four months after the treatment, he became transfusion independent, and has maintained hemoglobin levels of around 13 g/dl until today. Case 2 is a 70-year-old female with acute myeloid leukemia with myelodysplasia-related changes. She had been on RBC transfusion of 4 units/month when she was started on DSX treatment in January, 2010. Two months after the treatment, she became transfusion-independent, and 5 months after treatment, blast cells completely disappeared in the peripheral blood, together with normalization of white blood cell and neutrophil counts. Achieving durable transfusion-independency and normalization of white blood cell count and differential with a single use of DSX is a very rare event. Prospective accumulation of more patients and research to understand the mechanism underlying these effects are clearly warranted.

[Fatal disseminated toxoplasmosis after unrelated bone marrow transplantation for myelodysplastic syndrome].

A 44-year-old man with myelodysplastic syndrome (RAEB-2) underwent allogeneic bone marrow transplantation from an unrelated donor after being conditioned with myeloablative regimen. Tacrolimus and short-term methotrexate were given for prophylaxis against graft-versus-host disease (GVHD). Engraftment was achieved on Day 17. He developed Grade II acute GVHD involving the skin and gastrointestinal tract and methylprednisolone (2 mg/kg) was initiated. On Day 60, he developed fever and liver dysfunction followed by diffuse interstitial infiltration of the lungs. Respiratory and cardiac failure rapidly progressed and the patient died on Day 66 despite treatment with antimicrobial agents and intravenous immunoglobulin. Autopsy findings revealed disseminated toxoplasmosis involving the lungs, heart, liver, gastrointestinal tract, and kidneys. Toxoplasmosis after allogeneic hematopoietic stem cell transplantation (HSCT) generally manifests as encephalopathy or brain abscess; however, disseminated disease has been sporadically reported. It should be recognized as a possible cause of rapidly progressing interstitial pneumonitis and cardiac dysfunction after allogeneic HSCT.

[Early onset of paralytic ileus caused by simultaneous administration of bortezomib and azole antifungals in multiple myeloma patients].

We herein report two patients (70- and 45-year-old men) with refractory multiple myeloma who developed paralytic ileus shortly after starting bortezomib therapy. Bortezomib (1.3 mg/m(2)) was given on days 1, 4, 8, and 11 with daily oral solution itraconazole or voriconazole. Twelve and 15 days after beginning the therapy, each patient developed paralytic ileus. Interestingly, no other signs of peripheral neuropathy such as fingertip numbness were observed at the onset of ileus. Sporadic cases of paralytic ileus after bortezomib therapy have been reported, most of which developed ileus after several courses of bortezomib therapy. Our cases developed paralytic ileus shortly after initiating bortezomib, strongly suggesting that autonomic neuropathy due to bortezomib was induced by the concomitant use of itraconazole or voriconazole.

[Comparison of the results of quantitative polymerase chain reaction for cytomegalovirus among laboratories].

While cytomegalovirus (CMV) antigenemia assay is generally used for the monitoring of CMV reactivation/diseases, plasma real-time polymerase chain reaction (PCR) can also be a promising methodology and it can be performed by commercially available laboratories. In this study, the results of plasma real-time PCR performed by three laboratories were compared with those of CMV antigenemia. In CMV antigenemia-positive patients (N=11), the results of PCR were positive in all cases examined by two laboratories, while one laboratory yielded positive results only in 6 patients. One of the 2 CMV antigenemia-negative patients yielded positive PCR results at two laboratories, but one laboratory did not show positive results. A per-sample analysis showed that, of 84 CMV antigenemia-negative samples, PCR yielded negative results in 44 samples, positive results in 11 samples at three laboratories and at one or two laboratories in the remaining samples. Of the 36 CMV antigenemia-positive samples, PCR yielded positive results in 21 samples at three laboratories and positive results in the remaining samples at one or two laboratories. Although copy number of CMV-DNA evaluated by PCR at 3 laboratories showed a significant correlation with CMV antigenemia values, median copy number of CMV-DNA showed significant differences among the laboratories. Based on these findings, it is suggested that plasma real-time PCR has a higher sensitivity than CMV antigenemia in detecting CMV reactivation. However, the results varied significantly among the laboratories, suggesting that standardization of the methods is warranted.

Interferon-alpha 2b-induced thrombocytopenia is caused by inhibition of platelet production but not proliferation and endomitosis in human megakaryocytes.

Human interferon (IFN)-alpha is the standard therapy for chronic hepatitis C to prevent its progression to liver cirrhosis and hepatocellular carcinoma. Thrombocytopenia is one of the major adverse effects of IFN-alpha and often leads to dose reduction or treatment discontinuation. However, there is little information on how IFN-alpha inhibits human megakaryopoiesis. In this study, we demonstrated that IFN-alpha did not inhibit colony formation of megakaryocytes from human CD34(+) hematopoietic stem cells. IFN-alpha did not inhibit endomitosis but did inhibit cytoplasmic maturation of megakaryocytes and platelet production in vitro. IFN-alpha suppressed the expression of transcription factors regulating late-stage megakaryopoiesis, such as GATA-1, p45(NF-E2), MafG. IFN-alpha also significantly reduced the number of human platelets but not megakaryocytes, and did not inhibit endomitosis of human megakaryocytes in immunodeficient NOD/Shi-scid/IL-2R gamma(null) (NOG) mice transplanted with human CD34(+) cells (hu-NOG). We also demonstrated that a novel thrombopoietin mimetic, NIP-004, was effective for treating IFN-alpha-induced thrombocytopenia in hu-NOG mice. From ultrastructural study, IFN-alpha inhibited the maturation of demarcation membranes in megakaryocytes, although NIP-004 prevented the inhibitory effects of IFN-alpha. These results defined the pathogenesis of IFN-alpha-induced thrombocytopenia and suggested possible future clinical applications for thrombopoietin mimetics.

The effect of a novel, small non-peptidyl molecule butyzamide on human thrombopoietin receptor and megakaryopoiesis.

BACKGROUND: Thrombocytopenia is a common problem in the management of patients with cancer and other conditions that affect hematopoietic cells. In previous clinical trials, the polyethylene-glycol-conjugated recombinant human megakaryocyte growth and development factor increased platelet counts in patients with idiopathic thrombocytopenic purpura and solid tumors undergoing chemotherapy. However, antibodies to polyethylene-glycol-conjugated recombinant human megakaryocyte growth and development factor develop in healthy volunteers and patients undergoing chemotherapy and cross-react with endogenous thrombopoietin. As a result, clinical development of polyethylene-glycol-conjugated recombinant human megakaryocyte growth and development factor was discontinued in 1998. The aim of this study was to identify an orally bioavailable human Mpl activator that does not develop autoantibodies against endogenous thrombopoietin. DESIGN AND METHODS: We screened our chemical library and created a novel non-peptidyl thrombopoietin receptor, Mpl activator named butyzamide. We evaluated the effect of butyzamide on megakaryopoiesis in vitro using Ba/F3 cells expressing Mpl and human hematopoietic stem cells. For the evaluation of its in vivo effect, we administered butyzamide orally to immunodeficient NOD/Shi-scid,IL-2R gamma(null) (NOG) mice transplanted with human fetal liver-derived CD34(+) cells and investigated the production of human platelets. RESULTS: Butyzamide specifically reacted with human Mpl and activated the same signal transduction pathway as thrombopoietin. However, unlike thrombopoietin, butyzamide did not react with murine Mpl and was shown to require the histidine residue in the transmembrane domain of Mpl for its agonistic activity. Butyzamide induced colony-forming unit-megakaryocytes and polyploid megakaryocytes from human CD34(+) hematopoietic progenitor cells, and its effects were comparable to those of thrombopoietin. When butyzamide was administered orally at the doses of 10 and 50 mg/kg for 20 days to NOG mice transplanted with human fetal liver-derived CD34(+) cells, the human platelet count increased by 6.2- and 22.9-fold, respectively. CONCLUSIONS: Butyzamide is an orally bioavailable human Mpl activator, and appears to have potential for clinical development as a therapeutic agent for patients with thrombocytopenia.

Daily oral verapamil before but not after rapid atrial excitation prevents electrical remodeling.

BACKGROUND: Intravenous verapamil has been reported to prevent electrical remodeling induced by rapid atrial excitation of several minutes to several hours. However, the clinical efficacy of verapamil when taken orally and daily remains controversial. PURPOSE: We attempted to demonstrate our hypothesis that if verapamil prevents calcium (Ca) overload, its efficacy would be greater when taken before, rather than after, the onset of rapid atrial excitation. METHODS: In 24 dogs, pacing and recording electrodes were sutured onto the right atrium. After a 5-day recovery period, rapid atrial pacing at 400 ppm was started, followed 2 days later by oral verapamil (8 mg/kg per day) in eight dogs (After group; A). In another eight dogs, oral verapamil administration was begun 1 week before the initiation of rapid pacing (Before group; B). In the remaining eight dogs, only rapid atrial pacing was started, without oral verapamil (Control group; C). We measured the effective refractory period (ERP) and conduction velocity (CV), and calculated wavelength (WL) at cycle lengths 200 and 300 ms on the day before (P0), and after 2 (P2), 7 (P7), 14(P14) days of rapid pacing. RESULTS: In response to rapid atrial pacing, ERP, CV, WL decreased and progressively and comparably in A and C (P<0.05 vs. P0). In contrast, in B, these parameters did not change significantly and remained greater than those in A and C (P<0.05). Moreover, the adaptation of ERP to rate was preserved only in B. The duration of atrial fibrillation (AF) was shorter in B than in A and C (P<0.05). The inducibility of AF tended to be lower, and the fibrillation cycle length was longer in B than in A and C. CONCLUSIONS: Oral verapamil started before but not after rapid atrial excitation prevents electrical remodeling. Verapamil may exert beneficial effects when it is taken during sinus rhythm, but not after more than 2 days of atrial tachyarrhythmia.

Real-time ultrasound-guided endoscopic surgery for putaminal hemorrhage.

OBJECT: Endoscopic surgery plays a significant role in the treatment of intracerebral hemorrhage. However, the residual hematoma cannot be measured intraoperatively from the endoscopic view, and it is difficult to determine the precise location of the endoscope within the hematoma cavity. The authors attempted to develop real-time ultrasound-guided endoscopic surgery using a bur-hole-type probe. METHODS: From November 2012 to March 2014, patients with hypertensive putaminal hemorrhage who underwent endoscopic hematoma removal were enrolled in this study. Real-time ultrasound guidance was performed with a bur-hole-type probe that was advanced via a second bur hole, which was placed in the temporal region. Ultrasound was used to guide insertion of the endoscope sheath as well as to provide information regarding the location of the hematoma during surgical evacuation. Finally, the cavity was irrigated with artificial cerebrospinal fluid and was observed as a low-echoic space, which facilitated detection of residual hematoma. RESULTS: Ten patients with putaminal hemorrhage>30 cm3 were included in this study. Their mean age (±SD) was 60.9±8.6 years, and the mean preoperative hematoma volume was 65.2±37.1 cm3. The mean percentage of hematoma that was evacuated was 96%±3%. None of the patients exhibited rebleeding after surgery. CONCLUSIONS: This navigation method was effective in demonstrating both the real-time location of the endoscope and real-time viewing of the residual hematoma. Use of ultrasound guidance minimized the occurrence of brain injury due to hematoma evacuation.

Ventricular septal rupture masquerading as coronary perforation during intervention for acute myocardial infarction.

Ventricular septal rupture is a serious complication of acute myocardial infarction. We experienced a case of septal rupture immediately after primary angioplasty with thrombolysis, whose angiographic findings were similar to those of coronary perforation. The progression of septal rupture was delineated by the serial angiograms.

Validation of NIH consensus criteria for diagnosis and severity-grading of chronic graft-versus-host disease.

To validate the National Institutes of Health (NIH) consensus criteria for chronic GVHD, we retrospectively reviewed 143 patients who developed GVHD later than 100 days after allogeneic hematopoietic stem cell transplantation. Their GVHD was reclassified and the severity was graded according to the criteria. Only four patients (2.8 %) could not be reclassified into any type of GVHD. In the remaining 139 patients, reclassified subtypes were late acute GVHD in 52 patients (37.4 %), classic chronic GVHD in 33 (23.7 %), and overlap syndrome in 54 (38.8 %). Of 87 patients with classic chronic GVHD or overlap syndrome, the severity was graded as mild in 21 patients (24 %), moderate in 53 (61 %), and severe in 13 (15 %). The proportions of moderate (70 %) and severe (20 %) disease were significantly higher in patients with overlap syndrome than those with classic chronic GVHD (46 and 6 %, respectively; P < 0.001). Univariate and multivariate analyses of subtypes and severity did not identify any significant prognostic values in any of the transplant outcomes, such as transplant-related mortality, overall survival, GVHD-specific survival, or discontinuation of systemic immunosuppressants. These findings suggest that the NIH consensus criteria are useful for classification of chronic GVHD, but have limited significance in predicting clinical outcomes. The validity of these criteria remains inconclusive, and future prospective studies will be required to refine them.