Dislocation is a Leading Cause of Decreased Survival Rate in Primary Total Hip Arthroplasty Performed by Low-Volume Surgeons: Long-Term Retrospective Cohort Study.

BACKGROUND: This study aimed to evaluate the complications and long-term survival of primary total hip arthroplasty (THA) performed by low-volume (LV) surgeons at a LV hospital. We also determined the relationship between complications and revisions. METHODS: This retrospective cohort study included 220 THAs in 194 patients treated at our institution between 1998 and 2008, who received a minimum of a 10-year follow-up. The median annual THA volume at this hospital was 23 procedures (range, 11-32), and the annual volume per surgeon ranged from 1 to 19. We investigated the 90-day mortality and rates of periprosthetic joint infections, dislocations, and periprosthetic fractures up to the last visit (median follow-up, 11.8 years). Kaplan-Meier survival was calculated with revision as the end point. RESULTS: Postoperative infections, dislocations, and fractures at any time during the follow-up period were reported for 1 hip (0.5%), 23 hips (9.8%), and 4 hips (1.8%), respectively. One death occurred within the first 90 days postoperatively. Fifteen hips required revision surgery, and the survival rate was 95.5% at 5 years and 94.1% at 10 years. Of 10 hips that required early revision surgery within 5 years after the index surgery, 9 were revisions to address recurrent dislocation. CONCLUSION: The risk of dislocation was high. A high number of patients who underwent THA by LV surgeons required early revision because of dislocation. To achieve optimal long-term survivorship, LV surgeons should consider measures to reduce the risk of dislocation.

A low-volume surgeon is an independent risk factor for leg length discrepancy after primary total hip arthroplasty: a case-control study.

PURPOSE: Leg length discrepancy (LLD) is one of the bothersome complications that reduce patient satisfaction after total hip arthroplasty (THA). This study aimed to investigate the independent risk factors of LLD after primary THA. METHODS: This is a case-control study of 163 THAs for 163 patients at our institution between April 2015 and March 2018. The relevant data about the general characteristics of the patients (age, sex, body mass index, and diagnosis), surgery (surgical approach, type of femoral stem fixation, and surgeon volume), and radiological findings (Dorr classification and pre-operative LLD) were reviewed to identify the risk factors of ≥ 5 mm post-operative LLD according to radiological measurement and to calculate odds ratios (OR) via logistic regression analysis. RESULTS: The median (interquartile) absolute value of post-operative LLD was 3.9 (2.3-7.4) mm, and 57 (35.0%) patients had LLD of ≥ 5 mm. After controlling for possible confounders, a low-volume surgeon was considered the only independent risk factor of post-operative LLD (adjusted OR: 8.26; 95% confidence interval: 3.48, 19.60; P < 0.001). Among the 103 patients performed by high-volume surgeons, 82 (79.6%) had LLD of < 5 mm, whereas among the 60 patients performed by low-volume surgeons, only 24 (40.0%) achieved LLD of < 5 mm (P < 0.001). CONCLUSION: A low-volume surgeon is associated with an increased risk of a post-operative LLD after primary THA, and the importance of measurements should be recognized to prevent post-operative LLD and achieve optimal outcomes. Moreover, surgeons must inform patients about the risk of developing LLD pre-operatively.

Expression of CD56 is an unfavorable prognostic factor for acute promyelocytic leukemia with higher initial white blood cell counts.

Expression of CD56 has recently been introduced as one of the adverse prognostic factors in acute promyelocytic leukemia (APL). However, the clinical significance of CD56 antigen in APL has not been well elucidated. We assessed the clinical significance of CD56 antigen in 239 APL patients prospectively treated with all-trans retinoic acid and chemotherapy according to the Japan Adult Leukemia Study Group APL97 protocol. All patients were prospectively treated by the Japan Adult Leukemia Study Group APL97 protocol. The median follow-up period was 8.5 years. Positive CD56 expression was found in 23 APL patients (9.6%). Expression of CD56 was significantly associated with lower platelet count (P = 0.04), severe disseminated intravascular coagulation (P = 0.04), and coexpression of CD2 (P = 0.03), CD7 (P = 0.04), CD34 (P < 0.01) and/or human leukocyte antigen-DR (P < 0.01). Complete remission rate and overall survival were not different between the two groups. However, cumulative incidence of relapse and event-free survival (EFS) showed an inferior trend in CD56(+) APL (P = 0.08 and P = 0.08, respectively). Among patients with initial white blood cell counts of 3.0 × 10(9)/L or more, EFS and cumulative incidence of relapse in CD56(+) APL were significantly worse (30.8% vs 63.6%, P = 0.008, and 53.8% vs 28.9%, P = 0.03, respectively), and in multivariate analysis, CD56 expression was an unfavorable prognostic factor for EFS (P = 0.04). In conclusion, for APL with higher initial white blood cell counts, CD56 expression should be regarded as an unfavorable prognostic factor.

Etanercept Promotes Bone Formation via Suppression of Dickkopf-1 Expression in Rats with Collagen-Induced Arthritis.

BACKGROUND: Various clinical reports suggest etanercept (ETN) has some efficacy in bone formation in rheumatoid arthritis (RA). To examine this effect, we investigated the gene expression of cytokines relevant to osteoblast/osteoclast differentiation, and evaluated histomorphometric findings in mature rats with collagen-induced arthritis (CIA). METHODS: Total RNA was extracted from knee joints with CIA after ETN or placebo administration. Subsequently, realtime-PCR was carried out to quantify the mRNAs encoding Wnt-1, Dickkopf-1 (DKK-1), receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegelin (OPG) and TNF (tumor necrosis factor)-alpha. In histomorphometric analysis, the infiltrating pannus volume and pannus surface, and the following items in contact with pannus surface were measured: osteoclast number, osteoid surface, osteoid volume and labeling surface. These were evaluated in the distal femur with CIA with or without ETN administration. RESULTS: TNF-alpha, RANKL and OPG mRNA expressions, linked to osteoclastogenesis, were not significantly different with or without ETN administration. ETN administration significantly increased Wnt-1 mRNA expression, the osteoblast promoter, and decreased DKK-1 mRNA expression, the Wnt signal inhibitor. In histomorphometric analysis, pannus volume, pannus surface and osteoclast number, parameters of bone destruction, were not significantly different among groups. Osteoid volume, osteoid surface and labeling surface, parameters of bone formation, increased significantly with ETN administration. CONCLUSION: Our results suggest that ETN suppresses DDK-1 expression, and, as a result, Wnt expression is promoted and osteoblastogenesis becomes more active, independent of the regulation of osteoclast activity. Marked bone formation is attributed to the fact that ETN directly promotes osteoblastogenesis, not as a result of suppressing osteoclastogenesis.

Long-term outcome and prognostic factors of elderly patients with acute promyelocytic leukemia.

Studies focused on elderly acute promyelocytic leukemia (APL) are relatively limited. To evaluate prognostic impact in elderly APL, we compared the long-term outcome of elderly APL patients (60-70 years) with younger patients (15-59 years) treated with all-trans retinoic acid combined with anthracycline and cytarabine in the Japan Adult Leukemia Study Group (JALSG) APL97 study. Of 283 evaluable patients, 46 (16.3%) were elderly who had more frequent lower platelet (P = 0.04), lower albumin (P = 0.006) and performance status 3 (P = 0.02), higher induction death rate due to differentiation syndrome (P = 0.03), and non-relapse mortality (NRM) during consolidation therapy (P = 0.001). Overall survival was significantly inferior in elderly patients (P = 0.005), but disease-free survival and cumulative incidence of relapse were not. Better therapeutic approaches should be considered to reduce NRM during induction and consolidation therapy in elderly APL. This study was registered at http://www.umin.ac.jp/ctrj/ under C000000206.

Intensified consolidation therapy with dose-escalated doxorubicin did not improve the prognosis of adults with acute lymphoblastic leukemia: the JALSG-ALL97 study.

We designed a treatment protocol for newly diagnosed adult acute lymphoblastic leukemia (ALL) in the pre-imatinib era, employing intensified consolidation therapy with a total of 330 mg/m² doxorubicin and adopting slightly modified induction and maintenance regimen of the CALGB 8811 study. Of 404 eligible patients (median age 38 years, range 15-64 years), 298 (74%) achieved complete remission (CR). The 5-year overall survival (OS) rate was 32%, and the 5-year disease-free survival (DFS) rate was 33%. Of 256 Philadelphia chromosome (Ph)-negative patients, 208 (81%) achieved CR and the 5-year OS rate was 39%, and 60 of them underwent allogeneic-hematopoietic stem cell transplantation (allo-HSCT) from related or unrelated donors during the first CR, resulting in 63% 5-year OS. Of 116 Ph-positive patients, 65 (56%) achieved CR and the 5-year OS rate was 15%, and 22 of them underwent allo-HSCT from related or unrelated donors during the first CR, resulting in 47% 5-year OS. In Ph-negative patients, multivariate analysis showed that older age, advanced performance status and unfavorable karyotypes were significant poor prognostic factors for OS and higher WBC counts for DFS. The present treatment regimen could not show a better outcome than that of our previous JALSG-ALL93 study for adult ALL.

The first case of feline Prototheca wickerhamii infection in Japan.

A 3-year-old castrated male domestic short-haired cat was presented with nodules on the left nasal wing and the left earflap. Prototheca cells were found after excision biopsy of one of the nodules located on the left earflap. The patient cat was generally in good condition without skin problems. Prototheca wickerhamii was isolated from all 6 masses after they were surgically nucleated. The cat was recovered two months after intervention with no recurrence of skin nodules. This report deals with the first case of feline protothecosis in Japan.

Dic (17;20) (p11;q11) preceded MLL gene amplification in a patient with de novo mixed-lineage leukemia.

We report a case of acute mixed-lineage leukemia, as seen in a 65 year-old female with MLL gene amplification and biallelic loss of wild type p53 gene. The diagnosis was based on the findings that her bone marrow (BM) blasts expressed cytoplasmic CD3 (cyCD3), B-lineage antigens and myeloid antigens accompanied by clonal rearrangements of IgH gene. The BM blasts consisted of small-sized peroxidase-negative blasts (97%) and large-sized peroxidase-positive blasts (3%). The BM blasts showed a complex "karyotype," including dic(17;20) (p11;q11), -5 and add (11q23). Add (11q23) abnormality was found in sideline karyotypes as well as the stemline abnormality of dic(17;20) (p11;q11). For the p53 gene, which is located at 17p13, fluorescence in situ hybridization analysis showed the loss of one of two p53 alleles. Furthermore, polymerase chain reaction-single-strand conformation polymorphism and following nucleotide sequencing showed that the p53 gene was mutated at codon 215, leading to an amino acid substitution from Ser to Arg. For the MLL gene, southern blot analysis showed that the MLL gene locus was amplified but not rearranged at its breakpoint cluster region, which is usually rearranged in balanced translocations with many partner genes. These findings suggest that MLL gene amplification may in this case be based on the genetic instability caused by the preceding biallelic loss of the wild type p53 gene.

Randomized trial of response-oriented individualized versus fixed-schedule induction chemotherapy with idarubicin and cytarabine in adult acute myeloid leukemia: the JALSG AML95 study.

A multicenter, prospective, randomized study was conducted to compare a response-oriented individualized remission induction therapy with a standard fixed-schedule induction therapy, using idarubicin (IDR) and cytarabine (Ara-C), in adult patients with acute myeloid leukemia (AML). Newly diagnosed patients with AML of age less than 65 were randomly assigned to receive either of the two schedules. Both groups received IDR (12 mg/m2) for 3 days and Ara-C (100 mg/m2) for 7 days. In the individualized group, if the bone marrow on day 8 did not become hypocellular with less than 15% blasts, patients received additional IDR for one more day and Ara-C for 2 or 3 more days. Patients achieving complete remission (CR) received the same post-remission therapy. The CR rate was 79.4% for the individualized group (n = 209) and 81.9% for the fixed group (n = 221) (p = 0.598). At a median follow-up of 81 months, 7-year predicted overall survival was 37% for the individualized group and 39% for the fixed group (p = 0.496), and 7-year predicted event-free survival was 22% for the individualized group and 23% for the fixed group (p = 0.546). Thus, the present study could not demonstrate any advantage of a response-oriented individualized induction therapy over a fixed-schedule induction therapy in this protocol setting.

Allogeneic stem cell transplantation versus chemotherapy as post-remission therapy for intermediate or poor risk adult acute myeloid leukemia: results of the JALSG AML97 study.

We prospectively compared allogeneic hematopoietic stem cell transplantation (allo-HSCT) with chemotherapy as a post-remission therapy in a multicenter trial (JALSG AML97) of adult patients with intermediate or poor risk acute myeloid leukemia (AML). Of 503 patients aged 15-50 years old registered between December 1997 and July 2001, 392 achieved complete remission (CR). CR patients classified in the intermediate or poor risk group using a new scoring system were tissue typed. Seventy-three with and 92 without an HLA-identical sibling were assigned to the donor and no-donor groups. Of 73 patients in the donor group, 38 (52%) received allo-HSCT during CR1 and 17 (23%) after relapse. Intention-to-treat analysis revealed that the relapse incidence was reduced in the donor group (52 vs. 77%; p = 0.008), and the disease-free survival (DFS) improved (39 vs. 19%; p = 0.016), but overall survival (OS) was not significantly different (46 vs. 29%; p = 0.088). The OS benefit was seen in the patients aged 36-50 years old (49 vs. 24%; p = 0.031), suggesting an advantage of allo-HSCT among older patients with leukemia that is more resistant to chemotherapy than that among younger patients.

A phase II, open-label, sequential-cohort, dose-escalation study of romiplostim in Japanese patients with chronic immune thrombocytopenic purpura.

This phase II, multicenter, open-label, sequential-cohort, dose-escalation study was designed to evaluate the safety and efficacy of romiplostim, a novel peptibody that increases platelet production, in Japanese patients with chronic immune thrombocytopenic purpura (ITP). Sequential cohorts of four patients each received romiplostim (1, 3, or 6 microg/kg) subcutaneously on days 1 and 8 of the dose-escalation phase. Patients who achieved platelet responses (doubling of baseline platelet counts to > or =50 x 10(9)/L) continued romiplostim weekly during the treatment-continuation phase. Romiplostim produced dose-dependent increases in mean and peak platelet counts. Five patients received romiplostim during the treatment-continuation phase, with platelet counts > or =50 x 10(9)/L maintained in approximately half of the weekly assessments. Romiplostim was well tolerated. No severe, serious, or life-threatening adverse events were reported. No binding antibodies to romiplostim or thrombopoietin were detected. Romiplostim is safe and well tolerated in Japanese patients with chronic ITP and is effective in producing platelet count increases, consistent with the results from studies in non-Japanese patients. On the basis of these findings, a starting dose of 3 microg/kg was recommended for phase III evaluation of romiplostim in Japanese patients with chronic ITP.

[Elevation of Epstein-Barr virus (EBV)-DNA in the peripheral blood of a patient with age-related EBV-associated B-cell lymphoproliferative disorder].

A 69-year-old man was admitted to our hospital with fever and right neck lymphadenopathy. A neck lymph node biopsy was performed. In the specimens, immunoblasts were present with an admixture of small T lymphocytes and macrophagocytes. Immunohistochemcal staining of immunoblasts was positive for CD20, CD30 and EBER. Epstein-Barr virus (EBV) serology showed elevated IgG antibody to VCA, and EBV DNA was detected in the peripheral blood. Since he showed latency II without immunodeficiency disease, we diagnosed age-related EBV-associated B-cell lymphoproliferative disorder (EBV-LPD) as a result of aging and EBV infection. He was treated with 6 courses of the CHOP regimen plus rituximab, and achieved complete remission. EBV-DNA became undetectable at remission. In age-related EBV-LPD, there is some possibility that EBV-DNA in the peripheral blood is valuable as a tumor biomarker.

Minodronic acid influences receptor activator of nuclear factor kappaB ligand expression and suppresses bone resorption by osteoclasts in rats with collagen-induced arthritis.

We investigated the inhibitory mechanism of bone resorption by minodronic acid in collagen-induced arthritis (CIA) in rats. Four groups of female Sprague-Dawley rats, aged 7 months, were studied: three groups of collagen-sensitized rats, including one placebo-administered group (CIA-P), and two minodronic acid-administered groups at 0.2 mg/kg/2 day (CIA-BIS) and 2.0 mg/kg/2 day (CIA-BIS10). These were studied with an additional untreated observation group (Cont group). Minodronic acid was administered orally a day after the initial sensitization. The femoral posteromedial condyle was analyzed histologically and immunohistologically 4 weeks after the initial sensitization. Western blotting was also performed to assess the receptor activator of nuclear factor kappaB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) expression of the knee joints. In CIA-P rats, many tartrate-resistant acid phosphatase (TRAP)-positive cells were found at the pannus-lining layer and the epiphyseal medulla. The bone-lining cells in the epiphyseal medulla and the cells in the pannus strongly expressed RANK and RANKL. In the minodronic acid-administered group, the number of TRAP-positive cells and the severity of arthritis were reduced. The reduction in the CIA-BIS10 group was significant compared with the CIA-P group (P < 0.05). Dosage-dependent reduction of RANK and RANKL expression was confirmed by immunohistology and Western blotting. With or without minodronic acid administration, no apoptotic cells were found in any groups using the TdT-mediated dUTP-biotinnick end labeling (TUNEL) method. The expression of OPG was not clear in all groups. These results demonstrated that minodronic acid inhibited the differentiation and the activation of osteoclasts not by inducing apoptosis but by inhibiting the RANKL-RANK system, and thereby suppressing bone resorption.

A randomized study with or without intensified maintenance chemotherapy in patients with acute promyelocytic leukemia who have become negative for PML-RARalpha transcript after consolidation therapy: the Japan Adult Leukemia Study Group (JALSG) APL97 study.

To examine the efficacy of intensified maintenance chemotherapy, we conducted a prospective multicenter trial in adult patients with newly diagnosed acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy. Of the 302 registered, 283 patients were assessable and 267 (94%) achieved complete remission. Predicted 6-year overall survival in all assessable patients and disease-free survival in patients who achieved complete remission were 83.9% and 68.5%, respectively. A total of 175 patients negative for PML-RARalpha at the end of consolidation were randomly assigned to receive either intensified maintenance chemotherapy (n = 89) or observation (n = 86). Predicted 6-year disease-free survival was 79.8% for the observation group and 63.1% for the chemotherapy group, showing no statistically significant difference between the 2 groups (P = .20). Predicted 6-year survival of patients assigned to the observation was 98.8%, which was significantly higher than 86.2% in those allocated to the intensified maintenance (P = .014). These results indicate that the intensified maintenance chemotherapy did not improve disease-free survival, but rather conferred a significantly poorer chance of survival in acute promyelocytic leukemia patients who have become negative for the PML-RARalpha fusion transcript after 3 courses of intensive consolidation therapy.

Severe hemorrhagic complications during remission induction therapy for acute promyelocytic leukemia: incidence, risk factors, and influence on outcome.

BACKGROUND: Even after the introduction of all-trans retinoic acid (ATRA), early hemorrhagic death remains a major cause of remission induction failure for acute promyelocytic leukemia (APL). METHODS: To investigate severe hemorrhagic complications during remission induction therapy with respect to incidence, risk factors, and influence on outcome. Results were analyzed for 279 patients enrolled in the APL97 study conducted by the Japan Adult Leukemia Study Group (JALSG). RESULTS: Severe hemorrhage occurred in 18 patients (6.5%). Although most of them were receiving frequent transfusions, the targeted levels of platelet counts (30 x 10(9)/L) and plasma fibrinogen (1.5 g/L) for this study were reached at the day of bleeding in only 71% and 40%, respectively. Nine of them succumbed to an early death, while the remaining nine patients eventually achieved complete remission (CR). The 5-yr event-free survival rate was 68.1% for those who did not suffer severe hemorrhage, and 31.1% for those who did (P < 0.0001). For patients who achieved CR, on the other hand, there was no difference in disease-free survival between patients with and without severe hemorrhage (P = 0.6043). Risk factor analysis identified three pretreatment variables associated with severe hemorrhage: initial fibrinogen level, white blood cell count, and performance status. Additionally, patients with severe hemorrhage were more easily prone to develop retinoic acid syndrome or pneumonia than patients without hemorrhage. CONCLUSIONS: These results indicate that fatal hemorrhage represents a major obstacle in curing APL, and that patients with such high-risk features may benefit from more aggressive supportive care.

A randomized, postremission comparison of four courses of standard-dose consolidation therapy without maintenance therapy versus three courses of standard-dose consolidation with maintenance therapy in adults with acute myeloid leukemia: the Japan Adult Leukemia Study Group AML 97 Study.

BACKGROUND: A major concern in the treatment of patients with acute myeloid leukemia (AML) is how to prevent disease recurrences. Although intensive consolidation therapy has proven useful, the effectiveness of maintenance therapy remains controversial. METHODS: Seven hundred eighty-nine patients ages 15-64 (median: 45 yrs) with de novo AML received induction therapy, which consisted of cytosine arabinoside (at a dose of 100 mg/m(2) on Days 1-7) and idarubicin (at a dose of 12 mg/m(2) on Days 1-3). The patients who achieved complete remission (CR) were then randomized into groups that received either four courses of standard-dose consolidation therapy without maintenance (Arm A) or three courses of standard-dose consolidation and six courses of maintenance therapy (Arm B). RESULTS: In total, 78.7% of patients achieved CR. The 5-year overall survival (OS) rate for the 789 eligible patients was 46.9%, and the disease-free survival (DFS) rate for the 621 patients who achieved CR was 32.9%. The 5-year OS rate for Arm A was 52.4%, and 58.4% for Arm B (P = 0.599). The 5-year DFS rate for the patients who achieved CR was 35.8% in Arm A and 30.4% in Arm B (P = 0.543). In analyzing the data according to the risk groups, no statistical difference was observed either in the 5-year OS rate or in the 5-year DFS rate between the 2 arms. CONCLUSIONS: In the current study, the Japan Adult Leukemia Study Group's conventional postremission therapy (three courses of standard-dose consolidation and six courses of maintenance therapy) was replaced successfully by a shorter duration of four courses of standard-dose consolidation therapy without the need for additional maintenance therapy.

[Splenic marginal zone lymphoma associated with antiphospholipid antibodies].

A 61-year-old woman experienced a high fever with anemia and APTT prolongation after suffering a herpes zoster virus infection. Physical examination revealed a large splenomegaly without lymphadenopathy. Laboratory evaluations were positive for lupus anticoagulant (LA) and monoclonal IgM-kappa protein. LA was associated with the presence of anti-beta2GPI antibody, anti-cardiolipin antibody, and anti-prothrombin antibody. Moreover, the results of factors IX, XI, and XII assays and CRP and FDP-E were disturbed. A splenectomy was performed, and a splenic marginal zone lymphoma (SMZL) was diagnosed. All hematological findings rapidly recovered after the splenectomy. No thrombotic events occurred after the splenectomy even though thrombosis prophylaxis was not performed. The clinical course suggested that the SMZL-producing antibody induced immunological abnormalities in the labolatory tests. Since the patient suffered disease progression soon after the splenectomy, an autologous peripheral stem cell transplantation with rituximab administration was performed.

Multicenter prospective study of interferon alpha versus allogeneic stem cell transplantation for patients with new diagnoses of chronic myelogenous leukemia.

We compared interferon alpha (IFN-alpha) therapy with stem cell transplantation (SCT) for patients with chronic-phase chronic myelogenous leukemia in a multicenter prospective study to investigate the optimal indication and timing of SCT, especially from HLA-matched unrelated donors. Of 257 eligible patients, 145 patients who were younger than 50 years were assigned to the IFN-alpha cohort (n = 87) or the SCT cohort (n = 58), according to family donor availability. In the IFN-alpha cohort, 52 patients received IFN-alpha and chemotherapy (the IFN1 group), and 35 patients received an SCT from an unrelated donor (the U-SCT group). In the SCT cohort, 47 patients received an SCT from a related donor (the R-SCT group). In the IFN1 group, 88% of the patients achieved a complete hematologic response, and 33% achieved a complete cytogenetic response. At a median follow-up period of 53 months, the predicted 6-year survival rate was 72% in the IFN1 group, 81% in the R-SCT group, and 81% in the U-SCT group. When overall survival was evaluated for the IFN-alpha and R-SCT cohorts by intention to treat according to family donor availability, the 6-year survival rates were 76% and 84%, respectively. When the outcomes of the U-SCT and IFN1 groups were compared, the survival rate of U-SCT group patients was significantly better than for IFN1 group patients without a major cytogenetic response and seemed better for IFN1 group patients younger than 35 years. Therefore, U-SCT may be recommendable to patients who fail to achieve a major cytogenetic response in IFN-alpha therapy and to younger patients.

Membranous nephropathy associated with donor lymphocyte infusion following allogeneic bone marrow transplantation.

Nephrotic syndrome after hematopoietic stem cell transplantation (HSCT) followed by donor lymphocyte infusion (DLI) has never been described. We report the case of a myelodysplastic syndrome (MDS) patient who developed nephrotic syndrome with membranous nephropathy 18 months after allogeneic HSCT and 4 months after DLI. A 50-year-old woman with MDS underwent allogeneic bone marrow transplantation from her HLA-matched brother. MDS relapsed 55 days after transplantation, donor lymphocytes were infused as adoptive immunotherapy, and complete remission was achieved. Four months after the third DLI, the patient developed nephrotic syndrome with proteinuria up to 9 g/day. Renal biopsy revealed granular deposits of immunoglobulin G along the glomerular basement membrane, and subepithelial electron-dense deposits. A diagnosis of membranous nephropathy was made. For maintenance of the immunotherapeutic effect of DLI, minimum doses of immunosuppressive therapy for decreasing proteinuria were administered, and improvement of nephrotic syndrome and persistent complete remission of MDS were achieved.