[Successful immunosuppressive therapy in female hemophilia A developing inhibitor after perioperative administration of factor VIII products].

A 62-year-old woman was diagnosed as a hemophilia A carrier (factor VIII activity 35%) on preoperative examination of an ovarian tumor. A total of 35,600 units of recombinant factor VIII products was administered perioperatively. On postoperative day 95, a subcutaneous hematoma formed and immunosuppressive therapy with prednisolone was started based on an APTT of 66 seconds, factor VIII (FVIII) activity of 3%, and FVIII inhibitor of 1 BU/ml. During this treatment, the patient was hospitalized due to ankle joint bleeds and required hemostatic treatment, but the inhibitor disappeared and FVIII activity recovered to 30% after postoperative day 438 with cyclophosphamide. F8 analysis revealed the patient carried a heterozygosity of p.Arg391Cys, which has previously been categorized as cross-reacting material (CRM)-positive severe hemophilia A. No high-risk mutations for inhibitor development were found. We also report the results of a desmopressin acetate hydrate test administered to the patient to prepare for future treatment in case of hemorrhage, since high-dose FVIII administration may have been a factor in inhibitor development.

A case of lymphomatoid granulomatosis with central nervous system involvement successfully treated with IFNα.

Lymphomatoid granulomatosis (LYG) is a rare Epstein-Barr virus (EBV)-driven B-cell lymphoproliferative disease affecting mainly extranodal sites such as the lung, central nervous system (CNS), skin, kidney, and liver. We report a case of low-grade LYG involving the CNS that was successfully treated with interferon alpha (IFNα). A 69-year-old woman developed necrotic erythema of the skin and was initially diagnosed with pyoderma gangrenosum based on skin biopsy. She showed a limited response to prednisolone. Approximately 6 months after the initial onset, low-grade LYG was diagnosed after detection of CNS lesions on brain biopsy. The whole blood EBV-DNA load determined by real-time polymerase chain reaction was slightly elevated. Two months into IFNα therapy, skin and CNS lesions had responded favorably and the EBV-DNA load decreased. IFNα plays an important role in treatment of LYG through its antiproliferative, immunomodulatory, and anti-EBV effects. To our knowledge, this is the first case report of successful treatment with IFNα in Japan. Further investigation is necessary to determine optimal use of IFNα for LYG.

[Use of pegylated granulocyte colony-stimulating factor in dose-adjusted EPOCH-R therapy].

Dose-adjusted (DA)-EPOCH-R causes profound neutropenia requiring relatively long hospital stays with multiple doses of granulocyte colony-stimulating factor (G-CSF). A single-dose pegylated G-CSF (PEG-G-CSF) has been used for the treatment of chemotherapy-induced neutropenia. We retrospectively examined 15 patients (median age 61, range 33-75 years) treated with DA-EPOCH-R. In the first cycle of the DA-EPOCH-R therapy, a G-CSF preparation was used, and since the second cycle, the G-CSF and PEG-G-CSF use groups were divided. The median length of hospitalization after starting chemotherapy in the second-cycle DA-EPOCH-R was significantly shorter with PEG-G-CSF group (n=9) of 9 (7-13) days compared with G-CSF group (n=6) of 18 (15-22) days (P<0.001). Risk factors of febrile neutropenia, such as bone marrow invasion, performance status, serum albumin, and history of febrile neutropenia at the first DA-EPOCH-R cycle or previous chemotherapy were not significantly different for both groups, and the incidence of febrile neutropenia in PEG-G-CSF and G-CSF groups was 2.6% and 46.9%, respectively. These analyses suggest that PEG-G-CSF can be combined with DA-EPOCH-R without compromising treatment outcomes as compared with the daily dose of G-CSF.

Beneficial tyrosine kinase inhibitor therapy in a patient with relapsed BCR-ABL1-like acute lymphoblastic leukemia with CCDC88C-PDGFRB fusion.

BCR-ABL1-like acute lymphoblastic leukemia (ALL) is a neoplasm of lymphoblasts committed to the B-cell lineage that lack the BCR-ABL1 translocation but show a pattern of gene expression very similar to that seen in ALL with BCR-ABL1 with poor prognosis. A 22-year-old female was diagnosed with common-B-cell-ALL positive for CD10, CD19, CD22, CD79a, CD34, HLA-DR, and TdT in January 2017, and achieved complete remission (CR) with induction therapy, followed by consolidation therapy and maintenance therapy. In March 2020, 6 months after the completion of maintenance therapy, she relapsed. Inotuzumab ozogamicin (IO) was administered, and on day 28, bone marrow evaluation showed a morphologic CR. She had an HLA-identical sibling, and transplantation in her 2nd CR was planned. Because her ALL had been identified as BCR-ABL1-like ALL with CCDC88C-PDGFRB fusion, she was treated with imatinib for 2 months accompanied by 2 intrathecal methotrexate therapies, and 1 course of L-asparaginase, vincristine, and prednisolone in an outpatient setting. MRD analysis revealed potent efficacy of 2 months imatinib therapy; IgH MRD decreased from 1 × 10-2 to 1 × 10-3, and CCDC88C-PDGFRB/104ABL from 37.3 to 0. It is earnestly desired that well-designed clinical trials of TKI in ABL class-mutant BCR-ABL1-like ALL be conducted in Japan.

[Interleukin-6-producing paraganglioma mimicking multicentric Castleman disease].

Multicentric Castleman disease (MCD) comprises a heterogeneous group of lymphoproliferative disorders. Interleukin 6 (IL-6) plays an important role in the MCD pathophysiology. Here, we report the case of a 17-year-old Japanese man who presented with fever, headache, fatigue, and weight loss, with normal blood pressure. A movable mass was palpated in his lower abdomen. Laboratory tests revealed microcytic anemia and hypoalbuminemia, with elevated IL-6, sIL-2R, and vascular endothelial growth factor. Computed tomography of the abdomen demonstrated a 55-mm-diameter pelvic tumor and enlarged mesenteric lymph nodes. MCD was suspected, and the pelvic tumor resected. After the operation, his blood pressure rose slowly, and resulted to seizures of posterior reversible encephalopathy syndrome. Evaluation of hypertension revealed that plasma norepinephrine and normetanephrine concentrations were elevated, and pathological examinations showed that the resected tumor was positive for IL-6 and chromogranin-A. Therefore, we diagnosed the patient with IL-6-producing paraganglioma with MCD-mimicking symptoms. Moreover, IL-6-producing pheochromocytoma and paraganglioma should be included in differential diagnoses of MCD, even in normotensive patients.

Complete response following toxic epidermal necrolysis in relapsed adult T cell leukemia/lymphoma after haploidentical stem cell transplantation.

Allogeneic hematopoietic cell transplantation (allo-HSCT) is considered the curative treatment option in patients with aggressive adult T cell leukemia/lymphoma (ATLL), but the treatment of relapse after allo-HSCT remains a major challenge. We report a case of ATLL that was treated with sequential mogamulizumab (MOG) and lenalidomide (LEN) for early relapse after allo-HSCT. A 73-year-old Japanese male with acute-type ATLL underwent haploidentical-HSCT with post-transplant cyclophosphamide. He attained a complete response. However, ATLL relapse was diagnosed by biopsy of skin lesions that appeared on day 67. Discontinuation of immunosuppressant therapy alone did not result in improvement of ATLL, however, the skin lesions disappeared after an immune response was induced by sequential MOG and LEN. Following MOG and LEN, very serious toxic epidermal necrolysis (TEN) developed requiring high-dose intravenous immunoglobulin and methylprednisolone pulse therapy. Although graft-versus-host disease exacerbated and progressed to TEN, a complete response was achieved after successful treatment of TEN. These agents may thus enhance anti-ATLL activity by immune modulation. Further investigation is necessary to determine the optimal use of MOG and LEN in relapsed ATLL after allo-HSCT.

Comparison of cyclosporine and tacrolimus combined with mycophenolate mofetil in prophylaxis for graft-versus-host disease after reduced-intensity umbilical cord blood transplantation.

Umbilical cord blood transplantation with a reduced-intensity conditioning regimen (RIC-UCBT) is used increasingly in patients who have comorbid organ functions and lack human leukocyte antigen-identical donors. We compared the outcomes in 35 patients who received mycophenolate mofetil plus cyclosporine (MMF/CSP, n = 17) or MMF plus tacrolimus (MMF/TAC, n = 18) for graft-versus-host disease (GVHD) prophylaxis after RIC-UCBT. Cumulative incidence of neutrophil engraftment was 94 and 89 % in MMF/CSP and MMF/TAC groups, respectively (p = 0.34). The incidence of pre-engraftment immune reaction did not differ between the MMF/CSP (41 %) and MMF/TAC (39 %, p = 1.00) groups; however, patients in the MMF/TAC group tended to have a lower incidence of grade II-IV acute GVHD than those in MMF/CSP group (28 vs 53 %, p = 0.11). Overall survival (OS) at 1 year was 43 and 60 % in MMF/CSP and MMF/TAC groups, respectively (p = 0.39). Progression-free survival, non-relapse mortality, and relapse rate were comparable between the two groups (p = 0.76, 0.59, and 0.88, respectively). In multivariate analyses, MMF/TAC GVHD prophylaxis was closely associated with improved OS, but not with incidence of engraftment and acute GVHD. These results suggest that more intensive GVHD prophylaxis with MMF/TAC decreased acute GVHD without affecting other clinical outcomes, resulting in improved OS after RIC-UCBT.

A case of refractory multiple myeloma with proliferation of large granular lymphocytes by lenalidomide treatment and its association with clinical efficacy.

A 72-year-old Japanese male was diagnosed as having monoclonal gammopathy of undetermined significance and was followed up without therapy. Three years later, the patient progressed to symptomatic multiple myeloma. Melphalan + prednisolone was administered as first-line chemotherapy for ~6 years. Since the patient was judged to exhibit refractory multiple myeloma, he subsequently received radiation therapy on the lumbar spine. The patient was enrolled in a clinical trial and received lenalidomide + lowdose dexamethasone (Rd) therapy. The patient achieved very good partial remission following four cycles of Rd. At this time, large granular lymphocytes (LGLs) increased to 25-40% of peripheral blood leukocytes, however, the LGLs were present in the blood (~8%) prior to lenalidomide treatment. By flow cytometry of surface antigens, it was revealed that the LGLs were positive for cluster of differnetiation (CD)2, 7, 8, 16, 56, and 57, and human leukocyte antigen-D related, however, were negative for CD3, 4 and 5, suggesting that these LGLs predominantly exhibited an natural killer (NK) cell phenotype. T-cell receptor ß gene rearrangement was not detected by polymerase chain reaction. A 51Cr release assay was performed to investigate whether the NK cells actually possessed activity. A low level of M protein was sustained for ~15 months. This implied the enhancement of immune activation during lenalidomide treatment. The present case study suggested that LGL cells induced by lenalidomide may contribute to long-term restraint of myeloma cells. This immune system component may contribute to disease control.

Association between thromboembolic events and the JAK2 V617F mutation in myeloproliferative neoplasms.

Thrombotic complications are a major cause of death in patients with Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), which are closely associated with the JAK2 V617F activating mutation. However, whether the presence of the JAK2 V617F mutation affects thrombotic risk is currently unknown, although some reports have suggested a variable association with thrombosis. Therefore, we investigated the association between JAK2 V617F and various complications, including thrombosis, in Japanese patients with MPNs. We assessed the JAK2 V617F status in 140 patients who were diagnosed or doubted as having some type of MPN by utilizing a JAK2 V617F-specific guanine-quenching probe. JAK2 V617F was detected in 31 of 51 patients (60.8%) with essential thrombocythemia, all 16 patients (100%) with polycythemia vera, 4 of 11 patients (36.4%) with primary myelofibrosis, 2 of 18 patients (11.1%) with other types of MPNs, and none of the 44 patients with doubted MPN. In the 78 patients with classical MPN, JAK2 V617F correlated with a leukocyte count ≥10,000/µl (p=0.046). Complications of thrombosis, hemorrhage, and leukemic transformation occurred in 21 (41.2%), 4 (25.0%), and 3 (27.3%) patients with classical MPN, respectively, and thrombotic events (TE) occurred more frequently in patients with JAK2 V617F than without (p=0.047). Based on these findings, initial screening for the JAK2 mutation and careful monitoring for thrombotic events should be performed in patients with MPN.

Donor-derived 47, XXY in an unrelated cord blood transplant recipient.

A 65-year-old Japanese male with therapy-related myelodysplastic syndrome was admitted for unrelated cord blood transplantation. A cord blood unit from a male donor was obtained from the Japan Cord Blood Bank Network. The patient then received a conditioning regimen consisting of fludarabine, intravenous busulfan, and total body irradiation. Successful engraftment was obtained. The bone marrow examination on day 28 revealed trilineage engraftment, and chimerism analysis by variable number of tandem repeat polymerase chain reaction confirmed complete donor chimerism. At that time, conventional cytogenetics of the bone marrow aspirate showed 20 out of 20 metaphases with the 47, XXY karyotype characteristic of Klinefelter syndrome. Klinefelter syndrome is the most common genetic cause of human male infertility with a reported prevalence of 0.1-0.2% in the general population. In Japan Cord Blood Bank Network, there is no informed consent from parents about the possibility that post-unrelated cord blood transplantation patient evaluation may reveal donor-origin inherited diseases including cytogenetic abnormality. It is desirable to have opportunities in Japan discussing whether parents will be notified of the possibility that post-unrelated cord blood transplantation evaluation may reveal donor-derived illness incidentally.

[Fatal zygomycosis caused by Mucor indicus after haplo-identical stem cell transplantation].

A 62-year-old woman with acute lymphoblastic leukemia in first complete remission was treated with unrelated cord blood transplantation, but exhibited primary graft failure. She then underwent HLA-haploidentical peripheral blood stem cell transplantation from her daughter. The conditioning regimen consisted of fludarabine 30 mg/m(2)/day for 6 days, intravenous busulfan 3.2 mg/kg/day for 2 days, and thymoglobulin 1 mg/kg/day for 2 days. Voriconazole was administered to prevent fungal infections. The patient achieved prompt hematopoietic recovery. Fever was observed 21 days after the second transplant, followed by sigmoid colon perforation and a liver space occupying lesion (SOL). A filamentous fungus was detected in a percutaneous biopsy of the liver SOL. In spite of changing the antifungal drug from voriconazole to liposomal amphotericin B, the patient died on day 41. The fungus was identified as Mucor indicus, a type of zygomycete. Although Mucor indicus inhabits soil, an infectious disease is extremely rare, and breakthrough infection after voriconazole prophylaxis had not been reported until now. It is mandatory to consider preventive antifungal treatment for drug-resistant fungal infectious diseases in patients after neutrophilic recovery with a strongly immunocompromised state after a HLA-haploidentical transplant.

A case of 8p11 myeloproliferative syndrome with BCR-FGFR1 gene fusion presenting with trilineage acute leukemia/lymphoma, successfully treated by cord blood transplantation.

The 8p11 myeloproliferative syndrome is a rare neoplasm associated with chromosomal translocations involving the fibroblast growth factor receptor 1 (FGFR1) gene located at chromosome 8p11-12. FGFR1 encodes a transmembrane receptor tyrosine kinase. The resultant fusion proteins are constitutively active tyrosine kinases that drive the proliferation of hematopoietic cells, whose uncontrolled growth can present as a myeloproliferative neoplasm. We report here the case of a 50-year-old man harboring the t(8;22)(p12;q11) chromosomal translocation in cells from both bone marrow and lymph nodes. He presented with acute leukemia and lymphoma with trilineage features. A novel mRNA in-frame fusion between exon 4 of the breakpoint cluster region (BCR) gene at chromosome 22q11 and exon 9 of FGFR1 gene on chromosome 8p11-12 was identified by reverse transcription polymerase chain reaction analysis and was confirmed by DNA sequencing. Because the patient was refractory to chemotherapy, cord blood transplantation was performed in progressive disease. It resulted in a successful outcome in which cytogenetic complete remission has been maintained for 2 years till date.

Successful treatment of small cell variant anaplastic large cell lymphoma with allogeneic peripheral blood stem cell transplantation, and review of the literature.

The small cell variant of anaplastic large cell lymphoma (ALCL) presents in a nearly identical manner to the more common ALK(+) primary ALCL, with the exception that it is more frequently associated with leukemic involvement, and the prognosis has been reported to be poor. We report a 40-year-old Japanese male who was diagnosed with small cell variant ALCL with peripheral blood involvement stage IVB, age-adjusted international prognostic index 3. Conventional cytogenetics of the bone marrow aspirate specimen showed abnormal metaphases with the following karyotype: 47, XY, +X, t(2;5)(p23;q35). The patient was treated with acute lymphoblastic leukemia-oriented intensive chemotherapy. He underwent allogeneic peripheral blood stem cell transplantation from his HLA-DR1 locus mismatch sister. Prior to transplant, the patient had residual lymphadenopathy considered to be in partial remission. As of August 2012, the patient has achieved 18 months of continuous complete remission (CCR), with a Karnofsky score of 100 %. We have identified a total of seven cases of small cell variant ALCL treated with allogeneic hematopoietic stem cell transplantation (HSCT) in the literature. Of these, no relapse was reported, and four patients were CCR more than 1 year. Allogeneic HSCT appears to represent a promising treatment option for small cell variant ALCL.

Unrelated cord blood transplantation for patients with adult T-cell leukemia/lymphoma: experience at a single institute.

We report the results of unrelated cord blood transplantation (UCBT) for patients with adult T-cell leukemia/lymphoma (ATLL) conducted in our single institute. Ten patients with ATLL (nine acute and one lymphoma-type) received UCBT during the period from August 2003 to July 2011. The median age at the time of diagnosis of ATLL was 51 years (range 37-64). The median period from diagnosis of ATLL to UCBT was 130 days (range 94-344). Conditioning regimens were myeloablative for six and reduced intensity for four. The median number of infused nucleated cells and CD34 positive cells were 2.52 × 10(7)/kg and 1.04 × 10(5)/kg, respectively. There was no engraftment failure. Three patients developed grade II acute graft versus host disease, and four developed grade III. The estimated 2-year overall survival was 40 % (95 % CI 12-67 %). Four of six chemosensitive patients prior to UCBT survived for 1035, 793, 712, and 531 days post-UCBT, respectively. There were no survivors among the four chemorefractory patients prior to UCBT. Our data indicates that UCBT is feasible and provides long-term survival in patients with chemosensitive ATLL.

Characterization of the light chain-restricted clonal B cells in peripheral blood of HCV-positive patients.

To investigate the association between hepatitis C virus (HCV) and B cell proliferation, we searched for the clonal B cells by flow cytometric analysis of the surface immunoglobulin kappa (kappa):lambda (lambda) light chain ratios of the circulating B (CD19+) cells in 240 HCV-positive patients and 150 negative controls with liver diseases. Clonal B cells with light chain restriction (kappa:lambda ratio >3:1 or <1:2) were analyzed for CD5 expression and the presence of monoclonal immunoglobulin heavy-chain (IGH) gene rearrangements and the t(14;18) chromosomal translocation. Clonal B cells were detected in 7 cases with HCV (2.9%), but was never detected in the controls (p < 0.05). Of the 7 cases, all had monoclonal IGH gene rearrangements and one had the t(14;18) chromosomal translocation. These HCV-related clonal B cells are not uniform in the intensity of CD5 expression and showed no increase in the frequencies of CD5+ population compared with non-clonal B cells. No "chronic lymphocytic leukemia-phenotype" cells were found. The loss of clonality was observed in 2 cases treated with interferon and in one case treated with splenectomy. The longitudinal study is required to determine whether these circulating clonal B cells progress to lymphoproliferative disorders in future or not.

Periostin and bone marrow fibrosis.

Periostin is a secreted protein that shares structural homology with the insect axon guidance protein fasciclin 1. Periostin is expressed predominantly in collagen-rich fibrous connective tissues that are subjected to constant mechanical stresses. We have shown previously that periostin is a novel component of subepithelial fibrosis in bronchial asthma. Here, we investigated the relationship between periostin and bone marrow (BM) fibrosis. Periostin was expressed in the stroma and stromal cells of BM fibrosis specimens and to a great extent its expression levels correlated closely to the grade of fibrosis, as estimated by silver staining. However, in the present study, we found no relationship between plasma periostin levels and the extent of BM fibrosis. We also demonstrated that periostin is secreted by human BM hTERT stromal cells and that its secretion is enhanced by TGF-beta, a cytokine produced by clonal proliferation of megakaryocytes and/or monocytes. These results indicate that periostin is a component of BM fibrosis and that it may play a role in the disease progression.

[Relapse of autoimmune hemolytic anemia in Evans syndrome after thymectomy for pure red cell aplasia].

A 81-year-old woman was referred to our hospital with pure red cell aplasia (PRCA) associated with a thymoma in May 2005. She had previously suffered from Evans syndrome which had been improved by prednisolone in 1999. She underwent a thymectomy, however her anemia subsequently got worse. Reticulocytopenia was noted and a marrow erythroid series was aplastic. Furthermore, both direct and indirect Coombs tests were positive, and the serum haptoglobin level was low. Based on these findings, the patient was diagnosed as having PRCA complicated with relapsed autoimmune hemolytic anemia (AIHA). The PRCA and AIHA were successfully treated with prednisolone and cyclosporine. To our knowledge, only one case of the PRCA complicated with AIHA after thymectomy has been reported. FoxP3 positive regulatory T-cells (Treg), which maintain immunological self-tolerance, were readily detectable in the excised thymoma. Thus, thymectomy resulted in removal of the Treg pool and might explain the autoimmune activation, believed to be one of the mechanisms of the post-thymectomy recurrence of the AIHA in this case.

Promyelocytic crisis of chronic myelogenous leukaemia during imatinib mesylate treatment.

An untreated 66-year-old woman with chronic myelogenous leukaemia (CML) in the chronic phase was initially given imatinib mesylate, rapidly achieving a good cytogenetic response with treatment. However, acute promyelocytic leukaemia complicated by a disseminated intravascular coagulation occurred 9 months after beginning imatinib treatment. Promyelocytic crisis of CML was diagnosed by demonstration of both BCR/ABL and PML/RAR alpha chimeric genes in leukaemic cells by karyotypic and fluorescence in situ hybridization analysis. Clonal evolution with addition of the PML/RAR alpha translocation may have arisen in the early chronic phase of CML, with expansion of this clone during imatinib treatment. Promyelocytic crisis of CML is rare; furthermore, we know of no previous report of promyelocytic crisis occurring during treatment with imatinib.

Simultaneous hepatic relapse of non-Hodgkin's lymphoma and hepatocellular carcinoma in a patient with hepatitis C virus-related cirrhosis.

We report a 66-year-old man with hepatitis C virus (HCV)-related cirrhosis and simultaneous hepatic relapse of non-Hodgkin's lymphoma (NHL) and of hepatocellular carcinoma (HCC). Although the liver is frequently involved by NHL, hepatic colocalization of NHL and HCC is rarely detected by imaging techniques. HCV has been suggested to be lymphotrophic as well as hepatotrophic, and therefore has attracted speculation about a causative role in some cases of lymphoma. The patient had a past history of cutaneous diffuse large B cell lymphoma (DLBCL) in concurrence with HCC 32 months previously. Complete remission (CR) had been maintained for both diseases until February 2004, when ultrasonography and computed tomography (CT) showed multiple liver tumors. Two of these, appearing hyperattenuating in the arterial phase of contrast-enhanced CT, were diagnosed histopathologically as HCC, and treated with radiofrequency ablation. The other tumors, hypoattenuating in the portal phase CT, were diagnosed histopathologically as DLBCL, and treated with cyclophosphamide, tetrahydropyranyl-Adriamycin, vincristine and prednisolone (THP-COP) in combination with rituximab. CR was achieved for both DLBCL and HCC. Given the previously demonstrated immune system tropism and perturbation by HCV, the virus might have contributed to the occurrence of the NHL as well as the HCC.

Reduced neutrophil CD10 expression in nonhuman primates and humans after in vivo challenge with E. coli or lipopolysaccharide.

CD10, also known as neutral endopeptidase or CALLA, is a major metalloproteinase that regulates levels of biologically active peptides that initiate inflammatory, cardiovascular, and neurogenic responses. Relative tissue expression levels of CD10, its peptide substrates, and their receptors constitute the basic regulatory mechanism. Neutrophils contain abundant CD10 and are rapid responders to an inflammatory septic challenge. Expression of neutrophil surface antigens in response to inflammation was studied in the primate model of Escherichia coli-mediated sepsis and in human volunteers injected with lipopolysaccharide (LPS). There was a rapid and profound (up to 95%) reduced baboon neutrophil CD10 expression in response to E. coli injections of 5.71 x 106 CFU/kg to 2.45 x 109 CFU/kg that gradually resolved to preinjection levels. The reduction was both dose and time dependent. Reduced CD10 antigen on mature baboon neutrophils and bands was observed by immunohistochemistry. Human volunteers challenged with 4ng/kg LPS experienced transient chills, nausea, fever, and myalgia. Up to approximately 20% of their neutrophils had reduced CD10 expression, peaking at 2 to 8 h after injection. By 24 h, neutrophil CD10 expression resolved to preinjection levels. In contrast, in both the baboon and human studies, other neutrophil surface antigens were only slightly decreased (CD11a) or increased (CD11b, CD18, CD35, CD66b, and CD63). These data present the novel observation that neutrophil CD10 expression decreases significantly in response to in vivo inflammatory challenge. This decrease appears to be unique to CD10 and may contribute to a reduced regulation of bioactive peptides released in response to inflammatory challenge.