A retrospective analysis of treatment outcomes in adult T cell leukemia/lymphoma patients with aggressive disease treated with or without allogeneic stem cell transplantation: A single-center experience.

Adult T cell leukemia/lymphoma (ATL) is an aggressive peripheral T cell neoplasm with very poor prognosis. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been reported as a curative treatment modality for ATL. However, there are no reports comparing chemotherapy alone with allo-HSCT in ATL. In this report, we retrospectively analyzed data for patients treated with (n = 29, median age 55 years) or without allo-HSCT (n = 37, median age 58 years) for ATL in Kagoshima University Hospital, located in one of the most endemic areas of human T cell lymphotropic leukemia virus type 1 infection. Forty patients (61%) started coordination for allo-HSCT. Ten patients (34.4%) received allo-HSCT while in complete remission (CR), whereas the others were not in CR. Twenty-five patients (86.2%) received reduced-intensity conditioning, and the others received myeloablative conditioning. With a median follow-up period for survivors of 41 months (range, 5 to 125 months), the 3-year overall survival (OS) rate from first chemotherapy for all patients (with or without allo-HSCT) was 35.2%. The 3-year OS from first chemotherapy for patients who received allo-HSCT or only chemotherapy was 44.9% and 27.7%, respectively. Univariate analyses revealed that high serum soluble IL-2 receptor (sIL-2R) levels (≥ 2000 U/mL) just before the conditioning regimen and progressive disease (PD) status at HSCT (according to Japan Clinical Oncology Group Study 0907 criteria) were significant risk factors for OS in the allo-HSCT group. Multivariate analyses revealed that PD status was a significant risk factor for OS in the allo-HSCT group. In the chemotherapy-only group, the 3-year OS rate was 61.5% (95% CI, 30.8% to 81.8%) in patients with serum sIL-2R levels < 2000 U/mL for > 3 months. In contrast, the 3-year OS rate was 5.7% (95% CI, .4% to 22.4%) in patients who did not achieve serum sIL-2R levels < 2000 U/mL for >3 months. Our single-center cohort experience indicates that chemosensitivity is the most important prognostic factor for OS in ATL patients and the use of allo-HSCT is limited in chemorefractory patients with aggressive ATL disease. In the chemosensitive patients, allo-HSCT demonstrated a tendency toward better OS. Further clinical studies are warranted to determine optimal treatments for patients who are less sensitive to conventional chemotherapy.

Assessment of peripheral blood CD4+ adenosine triphosphate activity in patients with rheumatoid arthritis.

OBJECTIVE: The ability of the ImmuKnow (Cylex) assay to predict the risk of infection in rheumatoid arthritis (RA) patients receiving synthetic or biological disease-modifying antirheumatic drugs (DMARDs) was examined. METHODS: The amount of adenosine triphosphate (ATP) produced by CD4+ cells in response to phytohemagglutinin was measured in whole blood from 117 RA patients without infection versus 17 RA patients with infection, and compared with results in 75 healthy controls. RESULTS: The mean ATP level was significantly lower in patients with infection compared to both healthy controls (P < 0.0005) and patients without infection (P = 0.040). Also, the mean ATP level in patients without infection was significantly lower than that in healthy controls (P = 0.012). There was no correlation between the ATP level and the Disease Activity Score in 28 joints. CONCLUSION: ImmuKnow assay results may be effective in identifying RA patients at increased risk of infection, but the results showed no correlation with RA activity. Larger studies are required to establish the clinical advantages of this assay in RA treatment.

Target epitopes of HTLV-1 recognized by class I MHC-restricted cytotoxic T lymphocytes in patients with myelopathy and spastic paraparesis and infected patients with autoimmune disorders.

Human T-cell lymphotropic virus type I (HTLV-1) causes adult T-cell leukemia/lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The different patterns of clinical diseases are thought to be linked to immunogenetic host factors. A variety of autoimmune diseases, such as Sjögren's syndrome, have been reported in persons infected with HTLV-1, although the precise relationship between these disorders and HTLV-1 infection remains unknown. There is no report on the repertoire of HTLV-1-specific CD8+ T-cells in HAM/TSP patients or carriers with autoimmune diseases, both characterized by an abnormal immune state. In this study, to characterize HTLV-1-specific CD8+ T-cells in asymptomatic HTLV-1 carriers, HAM/TSP patients and carriers with autoimmune diseases, we examined the frequency and diversity of HTLV-1-specific CD8+ T-cells using HTLV-1 tetramers. HTLV-1 Env-specific CD8+ T-cells were significantly more frequent in HAM/TSP and carriers with autoimmune diseases compared with asymptomatic HTLV-1 carriers, while the frequency of HTLV-1 Tax-specific CD8+ T-cells was not significantly different among them. CD8+ cells binding to HTLV-1 Tax tetramers in carriers with autoimmune diseases were significantly reduced compared with HAM/TSP patients. This study demonstrates the importance of CD8+ T-cells recognizing HTLV-1 Env-tetramers in HAM/TSP patients and carriers with autoimmune diseases, thereby suggesting that the diversity, frequency and repertoire of HTLV-1 Env-specific CD8+ T-cell clones may be related to the hyperimmune response in HAM/TSP and carriers with autoimmune diseases, although different immunological mechanisms may mediate the hyperimmunity in these conditions.

Soluble CD22 as a tumor marker for hairy cell leukemia.

CD22 is an important immunotherapeutic target on B-cell malignancies, particularly hairy cell leukemia (HCL), but its soluble extracellular domain, sCD22, has not yet been reported in the blood. By immunoaffinity and enzyme-linked immunosorbent assay techniques using anti-CD22 monoclonal antibodies, we identified the 100-kDa extracellular domain of CD22 and an 80-kDa processed form in serum of patients with HCL. The median sCD22 level measured by enzyme-linked immunosorbent assay was 18 ng/mL for 93 patients with HCL. sCD22 levels varied from 2.1 to 163 ng/mL and were higher (P < .001) than 23 normal donors (median, 0.6 ng/mL). More than 95% of normal donors had sCD22 levels less than 1.9 ng/mL. sCD22 levels were proportional to concentrations of circulating HCL cells (P = .002), and HCL spleen size (P < .001). sCD22 levels normalized with complete but not partial response to treatment. sCD22 levels up to 300 ng/mL had less than a 2-fold effect on the cytotoxicity of the anti-CD22 recombinant immunotoxin BL22. sCD22 levels may be useful to follow in patients with HCL and may be more specific than sCD25 in patients with CD22(+)/CD25(-) disease. Trials are listed on www.cancer.gov as NCT00002765, NCT00021983, NCT00074048, NCT00085085, NCT00337311, and NCT00462189.

Correction to: Treatment of aggressive adult T-cell leukemia/lymphoma: a retrospective study in a hospital located in HTLV-1 highly endemic area.

In the original publication of the article, Table 5 was published with incorrect contents. The correct Table 5 is given in this correction.

Treatment of aggressive adult T-cell leukemia/lymphoma: a retrospective study in a hospital located in HTLV-1 highly endemic area.

Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell neoplasm associated with the human T-cell leukemia virus type-I (HTLV-1); prognosis still remains very poor. We retrospectively reviewed the treatment of 198 patients with acute-, lymphoma- and unfavorable chronic-type ATL (aggressive ATL) diagnosed from 2005 to 2014 in a hospital located in an area of Japan in which HTLV-1 is highly endemic. One-hundred forty-three, and 35 patients were treated using OPEC/MPEC and VCAP-AMP-VECP, respectively. OPEC/MPEC was mainly used until around 2010, and gradually switched to VCAP-AMP-VECP, especially for younger patients. The 2-year overall survival for patients treated by VCAP-AMP-VECP was significantly higher than that using OPEC/MPEC for patients < 70 years old (y.o.), but not for patients ≥ 70 y.o. A less intensive chemotherapy OPEC/MPEC could be performed without reducing dose intensity, even in elderly patients, and its therapeutic outcome is not inferior to that of VCAP-AMP-VECP. It is difficult to draw definite conclusion from this small retrospective study; however, OPEC/MPEC may represent an alternative option for elderly patients with aggressive ATL.

Allogeneic stem cell transplantation for refractory adult T-cell leukemia using a non-T-cell-depleted HLA-incompatible family donor graft, with reference to the grown-up child donor to parent recipient setting: report of a pilot study.

To increase the availability of alternative stem-cell donors for patients with adult T-cell leukemia (ATL), we examined the feasibility of HLA-incompatible family transplantation, especially from a grown-up child (donor) to a parent (recipient). Since January 2004, seven patients with advanced-phase ATL (three males and four females, median age 59 years), for whom a timely HLA-compatible donor was unavailable, were enrolled. All patients received allografts from their HLA-incompatible sons with reduced-intensity conditioning stem cell transplantation (RIST). Combined graft-versus-host disease (GVHD) prophylaxis involved cyclosporine A or tacrolimus, mycophenolate mofetil or corticosteroid, and short-term methotrexate. All patients achieved prompt engraftment, and there was no 100-day relapse-related mortality. Only one patient had grade-IV acute-GVHD, but this was resolved. The median follow-up period was 251 days (range 112-1,018 days), and the estimated 1-year overall and 1-year progression-free survival rates were 57.1 and 28.6%, respectively. Four patients died, with causes of death being relapse (n = 2), transplantation-associated microangiopathy (n = 1), and septicemia (n = 1). Three are currently alive: two are in complete remission and one has stable disease. Despite a high rate of relapse, RIST using an allograft from an HLA-incompatible grown-up child donor may be feasible for patients with advanced-phase ATL, and may prolong survival.

Acute lung Injury in a healthy donor during mobilization of peripheral blood stem cells using granulocyte-colony stimulating factor alone.

Granulocyte-colony stimulating factor (G-CSF), a hematopoietic growth factor, is widely used to accelerate recovery from neutropenia after severe chemotherapy, both decreasing the risk of infection and mobilizing peripheral blood stem cells. Adverse effects occur with G-CSF use in approximately 30% of cases, comprised predominantly of bone pain, headache, and general fatigue. Pulmonary toxicity is very rare. Here, we describe a healthy donor for allogeneic hematopoietic stem cell transplantation who developed acute lung injury (ALI) after 4 days of G-CSF administration. Among the serum cytokines examined, only Interleukin (IL)-1beta level was elevated in this case. As a high level of IL-1beta was detected at the onset of ALI, on day 4 after G-CSF administration, and decreased to below the level of detection on day 11, it is possible in a certain part that IL-1beta was involved in the onset of G-CSF-related ALI in the present case. Granulocyte-colony stimulating factor (G-CSF) is commonly administered to healthy donors to mobilize peripheral blood stem cells (PBSC) for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Adverse events from G-CSF use in healthy donors have been described in approximately 30% of cases, and are comprised predominantly of bone pain, headache, and general fatigue. Pulmonary complications caused by G-CSF include cough, dyspnea, and interstitial or alveolar pulmonary edema with mild-to-severe deterioration of blood oxygen level. Few cases of acute respiratory distress syndrome (ARDS) following G-CSF administration have been reported. The present report describes a healthy donor for allo-HSCT with acute lung injury (ALI) after 4 days of G-CSF administration. The cytokine-related mechanisms of G-CSF administration that contribute to ALI are discussed.

Case of a patient with progressive adult T-cell leukemia/lymphoma treated successfully by reduced-intensity conditioning stem cell transplantation from an HLA-incompatible related donor.

A 61-year-old man with progressive adult T-cell leukemia/lymphoma (ATLL) successfully received reduced-intensity conditioning stem cell transplantation (RIST) without T-cell depletion (TCD) from his HLA-incompatible son, who had negative results for human T-lymphotropic virus type 1 (HTLV-1) (1-locus, 1-allele mismatch in the graft-versus-host [GVH] direction; 2-loci, 1-allele mismatch in the host-versus-graft direction). The preparatory regimen consisted of fludarabine, busulfan, and rabbit antithymocyte globulin. GVH disease (GVHD) prophylaxis consisted of short-term administration of methotrexate, tacrolimus, and methylprednisolone. The patient achieved complete donor chimerism on day 30 after transplantation. On approximately day 50 the patient started to experience steroid-refractory skin GVHD (grade IV), which was successfully managed with basiliximab (anti-CD25 monoclonal antibody) and mycophenolate mofetil (MMF). Serial analysis of HTLV-1 proviral load by quantitative polymerase chain reaction analysis using whole peripheral blood demonstrated undetectable levels from day 90. At the time of this writing the patient had been in complete remission for more than 16 months. The results in this case suggest the potential of non-TCD RIST from an HLA-incompatible relative donor as an alternative source of hematopoietic stem cells even for an elderly patient with advanced ATLL. In addition, basiliximab combined with MMF may be effective for the treatment of steroid-refractory skin GVHD without deteriorating the graft-versus-ATL effect.

HTLV-I Tax protein inhibits apoptosis induction but not G1 arrest by pyrrolidinedithiocarbamate, an anti-oxidant, in adult T cell leukemia cells.

OBJECTIVE: We examined the anti-tumor effect of pyrrolidinedithiocarbamate (PDTC) on HTLV-1-infected T clones and the mechanism of HTLV-1 Tax protein inhibition of PDTC-induced apoptosis. MATERIALS AND METHODS: Tax-nonproducing clones S1T and Su9T01, Tax-producing clones K3T and F6T, and Tax cDNA stably transfected S1TcTax clones S1TcTax04 and S1TcTax05 were examined for PDTC inhibition of thymidine incorporation and apoptosis induction by ISEL method. In addition, S1TcTax clones were analyzed by DNA histography and DNA fragmentation and also examined for p53, p21, or Bax protein expression by Western blot. RESULTS: PDTC inhibited thymidine incorporation of all four HTLV-1-infected T cells in a similar dose-dependent manner, but K3T and F6T were more resistant than S1T and Su9T01 in apoptosis induction. S1TcTax clones also showed resistance to PDTC-induced apoptosis as compared to Tax-nonproducing S1T and S1Tneo. DNA histography demonstrated that PDTC induces G1 arrest and apoptosis in S1T and S1Tneo, and that S1TcTax clones are also sensitive to PDTC in G1 arrest but resistant in apoptosis induction. DNA fragmentation also demonstrated ladder formation only in S1Tneo but not in S1TcTax04. Western blots demonstrated higher expression of p53 and p21 proteins in S1Tneo than in S1TcTax04 during whole phase after PDTC stimulation with moderate enhancement in S1Tneo but small in S1TcTax04. Bax protein expression was detected only at early phase in S1Tneo but was not detected in S1TcTax04. CONCLUSION: These findings suggest that PDTC-induced apoptosis is related with Bax, and that G1 arrest is possibly related with p21. Tax might inhibit apoptosis induction mainly via inhibition of Bax expression preceded at least in part by p53 inhibition.

Effects of exogenous interleukin-7 on CD8(+) T-cell survival and function in human T-cell lymphotropic virus type 1 infection.

Interleukin-7 (IL-7) mediates T-cell homeostasis through its effects on T-cell development, survival and function. In human T-cell lymphotropic virus type 1 (HTLV-1) infection, which is causally implicated in adult T-cell leukemia (ATL), the efficiency with which CD8(+) cytotoxic T-lymphocytes (CTLs) clear HTLV-1-infected cells mediates viral control and may be related to disease progression. We report here that CD127 expression in CD8(+) T-cells is independently related to disease status, and that exogenous IL-7 enhances CD8(+) T-cell survival and clearance of HTLV-1 infected cells in vitro. We conclude that CD127 down-regulation may be associated with disease status in HTLV-1 infection, and propose that exogenous IL-7 may be useful immunotherapy or cytokine adjuvant for an anti-ATL therapeutic vaccine.

Programmed death-1 (PD-1)/PD-1 ligand pathway-mediated immune responses against human T-lymphotropic virus type 1 (HTLV-1) in HTLV-1-associated myelopathy/tropical spastic paraparesis and carriers with autoimmune disorders.

Human T-lymphotropic virus-1 (HTLV-1) causes HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia-lymphoma in individuals with dysfunctional immune responses. In this study, to characterize the HTLV-1-specific cytotoxic T lymphocyte (CTL) populations in asymptomatic HTLV-1 carriers (ACs), HAM/TSP patients, and carriers with autoimmune disorders (CAIDs), we examined the role of programmed death-1 and its ligand (PD-1/PD-L1) in HTLV-1-specific CTL functions using an HTLV-1 Tax/HLA-A*0201 tetramer and an HTLV-1 Tax/HLA-A*2402 tetramer. Interestingly, the percentage of HTLV-1 Tax301-309/HLA-A*2402 tetramer(+)CD8(+) cells expressing PD-1 in ACs was significantly higher than the percentage of HTLV-1 Tax11-19/HLA-A*0201 tetramer(+)CD8(+) cells expressing PD-1. PD-1 expression was significantly downregulated on HTLV-1-specific CTLs in HAM/TSP compared with ACs. PD-L1 expression was observed in a small proportion of unstimulated lymphocytes from ACs and was greater in ACs than in HAM/TSP and CAIDs after short-term culture. Furthermore, CTL degranulation was impaired in HAM/TSP, whereas anti-PD-L1 blockade significantly increased CTL function in ACs. Downregulation of PD-1 on HTLV-1-specific CTLs and loss of PD-L1 expression in HAM/TSP and CAIDs, along with impaired function of HTLV-1-specific CTLs in HAM/TSP, may underlie the apparently dysfunctional immune response against HTLV-1.

Novel cytotoxic isolated from Jamaican Hyptis verticillata jacq induces apoptosis and overcomes multidrug resistance.

BACKGROUND: Adult T-cell leukemia is an aggressive hematological malignancy with a poor clinical prognosis, and a rapid resistance to chemotherapy is rapid. MATERIALS AND METHODS: Cytotoxicity assay-directed fractionation identified a novel lignan-related agent, 4-methoxy-9-(3,4,5-trimethoxyphenyl)-8, 9 - dihydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-6(5H)-one (4-MTDND) from the Jamaican plant Hyptis verticillata jacq, and its effects on apoptosis, cell cycle and drug resistance were elucidated. RESULTS: The novel agent, 4-MTDND, exhibited cytotoxicity against myriad cancer types, with a wide therapeutic index of 30- to 40-fold, promoted G(2)/M arrest and up-regulated expression of pro-apoptotic proteins p53 and BAX, as well as enhanced activation of caspase-3, caspase-9 and poly (ADP ribose) polymerase, consistent with apoptosis induction. Multidrug-resistant cancer cells were as susceptible to 4-MTDND as their non-resistant control counterparts, with 4-MTDND having greater efficacy compared to standard chemotherapy agents etoposide and mitoxantrone. CONCLUSION: The novel cytotoxic agent 4-MTDND induces G(2)/M arrest and apoptosis in cancer cells possibly due to direct DNA damage or interference with topoisomerase II.

Efficacy of Waon therapy for fibromyalgia.

OBJECTIVE: Fibromyalgia syndrome (FMS) is a chronic syndrome characterized by widespread pain with tenderness in specific areas. We examined the applicability of Waon therapy (soothing warmth therapy) as a new method of pain treatment in patients with FMS. METHODS: Thirteen female FMS patients (mean age, 45.2+/-15.5 years old; range, 25-75) who fulfilled the criteria of the American College of Rheumatology participated in this study. Patients received Waon therapy once per day for 2 or 5 days/week. The patients were placed in the supine or sitting position in a far infrared-ray dry sauna maintained at an even temperature of 60 degrees C for 15 minutes, and then transferred to a room maintained at 26-27 degrees C where they were covered with a blanket from the neck down to keep them warm for 30 minutes. Reductions in subjective pain and symptoms were determined using the pain visual analog scale (VAS) and fibromyalgia impact questionnaire (FIQ). RESULTS: All patients experienced a significant reduction in pain by about half after the first session of Waon therapy (11-70%), and the effect of Waon therapy became stable (20-78%) after 10 treatments. Pain VAS and FIQ symptom scores were significantly (p<0.01) decreased after Waon therapy and remained low throughout the observation period. CONCLUSION: Waon therapy is effective for the treatment of fibromyalgia syndrome.

Case of a patient with Philadelphia-chromosome-positive acute lymphoblastic leukemia relapsed after myeloablative allogeneic hematopoietic stem cell transplantation treated successfully with imatinib and sequential donor lymphocyte infusions.

A 23-year-old man with Philadelphia-chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL) underwent myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) from his HLA-identical brother in first hematological remission following induction chemotherapy which included imatinib. He had no acute graft-versus-host disease (GVHD), and 4.5 months after HSCT, he had a molecular relapse (180,000 copies/mug RNA of minor bcr/abl transcripts (m-bcr/abl) without mutation in 22 sites including the p-loop region). Following discontinuation of cyclosporine A, imatinib (600 mg daily) was restarted and 4 days later donor lymphocyte infusion (DLI) (5 x 10(7)/kg of CD3(+) cells) was given. In 2 weeks, the marrow m-bcr/abl became undetectable. He received two further DLIs and imatinib was continued at a reduced dose of 400 mg a day. At the time of this report, he remains in complete hematological remission more than 33 months after allo-HSCT and persists in the second molecular remission for longer than 24 months. During this clinical course, he became positive for anti-nuclear antibody after second DLI, without any other manifestations of GVHD. The standard treatment for Ph(+) ALL relapsing after allo-HSCT still remains to be established. Imatinib in combination with DLI for early molecular relapse may be a promising option.

High prevalence of human T-lymphotropic virus type I carriers among patients with myelodysplastic syndrome refractory anemia with excess of blasts (RAEB), RAEB in transformation and acute promyelocytic leukemia.

We examined human T-lymphotropic virus type I (HTLV-I) infection among patients with myelodysplastic syndrome (MDS), refractory anemia with excess of blasts (RAEB)/RAEB in transformation (RAEBt) and acute myelogenous leukemia (AML). The study population consisted of 151 patients: 46 with MDS RAEB/RAEBt and 105 with AML (M1, n = 15; M2, n = 39; M3, n = 18; M4, n = 19; M5, n = 9; M6, n = 3; M7, n = 2). As a reference, we examined 92 patients with refractory anemia (RA) and 405 patients with cardiovascular diseases (CVD). Thirteen patients with RAEB/RAEBt (28.3%), 11 with AML (11.6%), 27 with RA (29.3%), and 45 with CVD (11.0%) were positive for HTLV-I. Seven AML patients with HTLV-I infection had M3 acute promyelocytic leukemia (APL). The prevalences of HTLV-I infection among patients with RAEB/RAEBt (P < 0.001), APL (P = 0.001), and RA (P < 0.001) were significantly higher than that in patients with CVD. The prevalences of HTLV-I infection were still significantly higher in patients with RAEB/RAEBt (P = 0.007), APL (P = 0.017) and RA (P < 0.001) than in those with CVD matched by sex and age. Platelet counts and survival times of RAEB/RAEBt patients with infection were significantly lower than those of patients without infection.

Clinical manifestations of human T lymphotropic virus type I-infected patients with systemic lupus erythematosus.

OBJECTIVE: Human T lymphotropic virus type I (HTLV-I) may be associated with some connective tissue autoimmune diseases, including systemic lupus erythematosus (SLE). To determine the relationship between HTLV-I infection and SLE, we examined the clinical manifestations of SLE patients with HTLV-I infection. METHODS: Eighty-nine patients with SLE were screened for antibodies to HTLV-I by electrochemiluminescence immunoassay. The presence of HTLV-I proviral sequences in peripheral blood mononuclear cells (PBMC) was determined by real-time polymerase chain reaction (PCR) quantification and Southern blotting analysis. The differences in clinical manifestations between HTLV-I-seropositive and seronegative patients with SLE were analyzed statistically. RESULTS: Fourteen of 89 (15.7%) patients were HTLV-I seropositive. All PBMC samples from 11 patients tested by PCR and 3 samples from 10 patients tested by Southern blotting analysis were positive for HTLV-I-related sequences. The age of HTLV-I-seropositive patients with SLE was significantly higher than that of seronegative patients (median 60 vs 42 yrs; p < 0.0005). The age at onset of SLE in HTLV-I-seropositive patients was also significantly higher than that of seronegative patients (median 45.5 vs 30 yrs; p <0.0005). The lymphocyte count in HTLV-I-seropositive SLE patients was significantly higher than that of seronegative patients (median 1740 vs 1066/microl; p = 0.027). The maintenance dose of prednisolone in HTLV-I-seropositive patients with SLE was significantly lower than that in seronegative patients (median 5 vs 9 mg/day; p = 0.012). CONCLUSION: This is the first report of the differences in clinical manifestations between SLE patients with and without HTLV-I infection. Our results suggest some involvement of HTLV-I in the pathogenesis of SLE.

High incidence of morphological myelodysplasia and apoptotic bone marrow cells in Behçet's disease.

Behçet's disease (BD) is a systemic inflammatory disorder of unknown etiology, and rarely complicated with myelodysplastic syndrome (MDS). In the present study, we investigated the morphological myelodysplasia and apoptotic rate of bone marrow cells in 15 patients with BD in comparison with MDS patients. Morphological myelodysplasia of bone marrow cells was detected in 53.3% of BD, but none showed chromosomal abnormalities. The apoptotic rate in BD patients (26.1 +/- 8.4%) was significantly higher in normal controls (11.3 +/- 2.4%; p < 0.005) and significantly lower in patients with MDS (50.8 +/- 14.0%; p < 0.0001). These findings suggest that myelodysplasia in patients with BD is more frequent than expected, and possibly due to excess induction of apoptosis of bone marrow cells in BD. However, the rate of apoptotic bone marrow cells is lower than MDS, which may explain the slight peripheral cytopenia in BD, distinct from that in MDS.