[Show abstract][Hide abstract] ABSTRACT: HLA-haploidentical 2 or 3-loci mismatched families are alternative donors for high-risk patients without HLA-matched donors. We retrospectively reviewed our case series of HLA-halpoidentical hematopoietic stem cell transplantations (haplo-HSCTs). Between Jul 2005 and Dec 2012, 25 patients (median age, 8 y; 13 ALL, 8 AML, 4 others) received haplo-HSCTs because of a worsening prognosis (i.e. induction failure, non-CR, or relapse after prior HSCT). Disease status was CR in 8 and non-CR in 17 patients. The 17 patients received myeloablative conditioning, while the 8 were given reduced-intensity conditioning because of their conditions (e.g. early relapse after prior HSCT). ATG was not administered in all but 3 patients. Tacrolimus and sMTX were used for prophylaxis GVHD and steroids were immediately given to prevent the onset of aGVHD. The 3-year OS and EFS were 35.6±10.0% and 31.3±10.1%, respectively (median follow-up, 49 mo); 14 patients died of their primary disease. Grade 3-4 aGVHD occurred in 7 patients, 2 of whom died of grade 4 aGVHD. Eleven patients had extensive cGVHD. While 4 of the 8 CR patients remained in CR, only 4 of the 17 non-CR patients achieved long-term CR (survival time, 6-89 mo). Haplo-HSCT was tolerable with strict control of infections and GVHD. However, further strategies for non-CR patients appear to be required.
No preview · Article · Feb 2014 · [Rinshō ketsueki] The Japanese journal of clinical hematology
[Show abstract][Hide abstract] ABSTRACT: Studies have suggested that bevacizumab has shown activity against various pediatric solid tumors. We, therefore, conducted a Phase I study of bevacizumab plus irinotecan in Japanese children with recurrent, progressive or refractory solid tumors.
The starting dose was bevacizumab 10 mg/kg over 60-90 min and irinotecan 125 mg/m(2) over 90 min intravenously on Days 1, 15 and 29. The dose of irinotecan was 340 mg/m(2) for patients receiving enzyme-inducing antiepileptic drugs. Treatment was repeated every 6 weeks for up to three courses in the absence of disease progression or unacceptable toxicity.
Of 11 patients, 9 (median age, 9 years) were fully assessable for toxicity and received 24 courses. Dose-limiting toxicities were Grade 2 diarrhea and Grade 4 neutropenia/thrombocytopenia in two of the five patients at dose level 1. No dose-limiting toxicities were observed in four patients at dose level -1 at bevacizumab 10 mg/kg and irinotecan 100 mg/m(2) (270 mg/m(2) for patients taking enzyme-inducing antiepileptic drugs). The maximum-tolerated dose was bevacizumab 10 mg/kg and irinotecan 100 mg/m(2). The most frequent non-dose-limiting toxicities were Grade 1 or 2 hypertension, bleeding and hematologic toxicity. One patient with optic nerve glioma had a partial response. Three patients with medulloblastoma, optic nerve glioma and diffuse intrinsic pontine glioma had stable disease.
Combination chemotherapy of bevacizumab plus irinotecan was well tolerated in children. We plan Phase II pediatric studies at doses of bevacizumab 10 mg/kg and irinotecan 100 mg/m(2) every 2 weeks (270 mg/m(2) for patients taking enzyme-inducing antiepileptic drugs).
Preview · Article · Sep 2013 · Japanese Journal of Clinical Oncology
[Show abstract][Hide abstract] ABSTRACT: The acute myeloid leukaemia (AML) 99 trial conducted previously in Japan for the treatment of de novo paediatric AML showed excellent results, with a 5-year overall survival (OS) and event-free survival (EFS) of 75·6% and 61·6%, respectively. To examine reproducibility of these results in another cohort, the outcome of 146 newly diagnosed AML paediatric patients prospectively registered in the Japan Association of Childhood Leukaemia Study (JACLS) from 2003 to 2006 was compared to that of 240 patients in the original AML 99 clinical trial. The 5-year EFS and OS achieved in the new cohort was 66·7 ± 4·0% and 77·7 ± 8·0% respectively, which were comparable to those obtained in the original AML 99 clinical trial, although less frequent core-binding factor (CBF) AML (29·5% vs. 37%) and an almost equal frequency of allogeneic haematopoietic stem cell transplantation (allo-HSCT) during first complete remission (16·5% vs. 19%) were observed. The 5-year EFS in patients with a normal karyotype (NK) (n = 35, 54·9 ± 15·1%) was inferior in the present cohort when compared to the original AML99 trial. This study confirmed the excellent outcome of the original AML99 protocol.
Full-text · Article · Aug 2012 · British Journal of Haematology
[Show abstract][Hide abstract] ABSTRACT: A 1-year-old girl with familial hemophagocytic lymphohistiocytosis underwent umbilical cord blood transplantation. On day 24, she developed renal failure, jaundice and hemolytic anemia, and we diagnosed transplantation-associated thrombotic microangiopathy (TMA). Despite discontinuation of tacrolimus, her condition became even worse. From day 25, we started to administer recombinant human soluble thrombomodulin (rTM). According to the recommendation of the pharmaceutical company, a dose reduction from 380 to 130 IU/kg/day in patients with renal failure, we administered rTM at the reduced dose during the first 2 days. Because the reduced dose was not effective, we administered rTM at the standard dose from day 27. Surprisingly, she began to recover from TMA on the next day, and we continued to administer rTM until day 109. She is alive without evidence of disease eighteen months after transplantation. Adverse events of rTM were severe gastrointestinal hemorrhage and hemorrhagic cystitis, and it was necessary to control hemorrhage by interruption of administration. This case report suggests that rTM may be effective for TMA. Moreover, alteration in the dosage schedule seems to be required according to the condition of patients. Further studies are needed to evaluate the effectiveness and an optimal dose of rTM as a treatment for TMA.
No preview · Article · Feb 2012 · [Rinshō ketsueki] The Japanese journal of clinical hematology
[Show abstract][Hide abstract] ABSTRACT: Although the therapeutic outcome of acquired aplastic anemia has improved markedly with the introduction of immunosuppressive therapy using antithymocyte globulin and cyclosporine, a significant proportion of patients subsequently relapse and require second-line therapy. However, detailed analyses of relapses in aplastic anemia children are limited.
We previously conducted two prospective multicenter trials of immunosuppressive therapy for children with aplastic anemia: AA-92 and AA-97, which began in 1992 and 1997, respectively. In this study, we assessed the relapse rate, risk factors for relapse, and the response to second-line treatment in children with aplastic anemia treated with antithymocyte globulin and cyclosporine.
From 1992 to 2007, we treated 441 children with aplastic anemia with standard immunosuppressive therapy. Among the 264 patients who responded to immunosuppressive therapy, 42 (15.9%) relapsed. The cumulative incidence of relapse was 11.9% at 10 years. Multivariate analysis revealed that relapse risk was significantly associated with an immunosuppressive therapy regimen using danazol (relative risk, 3.15; P=0.001) and non-severe aplastic anemia (relative risk, 2.51; P=0.02). Seventeen relapsed patients received additional immunosuppressive therapy with antithymocyte globulin and cyclosporine. Eight patients responded within 6 months. Seven of nine non-responders to second immunosuppressive therapy received hematopoietic stem cell transplantation and five are alive. Eleven patients underwent hematopoietic stem cell transplantation directly and seven are alive.
In the present study, the cumulative incidence of relapse at 10 years was relatively low compared to that in other studies mainly involving adult patients. A multicenter prospective study is warranted to establish optimal therapy for children with aplastic anemia.
[Show abstract][Hide abstract] ABSTRACT: Children with acute lymphoblastic leukemia (ALL) who fail to achieve complete remission (CR) after induction therapy (induction failure: IF) have a poor prognosis; however, there have been few prospective studies in patients with IF.
Between April 1997 and March 2005, 27 of 1,237 leukemic patients (2.2%) failed to achieve CR after four- or five-drug induction therapy. Twenty-three of these patients entered the F-protocol study, which mainly consisted of acute-myeloid-leukemia-oriented chemotherapy followed by scheduled hematopoietic cell transplantation (HCT).
Seventeen (73.9%) of the 23 patients responded to re-induction chemotherapy with CR. Of note, 15 (93.8%) of 16 patients with Philadelphia-chromosome-negative (non-Ph(+)) ALL achieved CR; in contrast, only 2 (28.6%) of 7 Ph(+) patients achieved CR. Fourteen (82.4%) of 17 patients remained in CR (CCR) until their scheduled HCT, 12 of the 14 with CCR underwent HCT as scheduled, and 6 patients remain in first CR after a median of 78 months (range, 49-107 months). The 5-year overall survival (OS) rates of 16 patients with non-Ph(+) and 7 patients with Ph(+) were 43.8 +/- 12.4% and 14.3 +/- 13.2%, respectively (P = 0.012). The 5-year OS rate of the 17 patients who obtained CR by re-induction therapy and the 6 who did not were 47.1 +/- 12.1% and 0%, respectively (P < 0.001).
Acute-myeloid-leukemia-oriented chemotherapy followed by scheduled HCT is a promising treatment strategy for non-Ph(+) ALL patients with IF.
No preview · Article · Jan 2010 · Pediatric Blood & Cancer
[Show abstract][Hide abstract] ABSTRACT: We cared 28 life limiting children with cancer in the past five years. Two patients died at home and the rest of them died at hospitals. Most children older than 11 years understood their disease. On the other hand, poor prognosis at the end stage was not noticed precisely to most of them. We recommended that they spend time with their families as long as possible. There were some problems associated with going back home. Those were as follows: a decision making was difficult for the patients because some of them were very young or unconcious not awake, not enough time for the patient's family to get ready for a home palliative care, or the patients who need frequent transfusions. In palliative care of children with the end of life stage cancer, it is essential that more co-medicals and other professions should be involved in order to strive for a good quality of life.
No preview · Article · Dec 2009 · Gan to kagaku ryoho. Cancer & chemotherapy
[Show abstract][Hide abstract] ABSTRACT: Post-transplant outcomes of hemophagocytic lymphohistiocytosis (HLH) patients were analyzed in Japan where Epstein-Barr virus (EBV)-associated severe forms are problematic.
Fifty-seven patients (43 familial HLH [12 FHL2, 11 FHL3, 20 undefined], 14 EBV-HLH) who underwent stem cell transplantation (SCT) between 1995 and 2005 were enrolled based on the nationwide registration.
Fifty-seven patients underwent 61 SCTs, including 4 consecutive SCTs. SCTs were employed using allogeneic donors in 93% of cases (allo 53, twin 1, auto 3). Unrelated donor cord blood transplantation (UCBT) was employed in half of cases (21 FHL, 7 EBV-HLH). Reduced intensity conditioning was used in 26% of cases. The 10-year overall survival rates (median +/- SE%) were 65.0 +/- 7.9% in FHL and 85.7 +/- 9.4% in EBV-HLH patients, respectively. The survival of UCBT recipients was >65% in both FHL and EBV-HLH patients. Three out of four patients were alive with successful engraftment after second UCBT. FHL patients showed a poorer outcome due to early treatment-related deaths (<100 days, seven patients) and a higher incidence of sequelae than EBV-HLH patients (P = 0.02). The risk of death for FHL patients having received an unrelated donor bone marrow transplant was marginally higher than that for a related donor SCT (P = 0.05) and that for UCBT (P = 0.07).
EBV-HLH patients had a better prognosis after SCT than FHL patients. FHL patients showed either an equal or better outcome even after UCBT compared with the recent reports. UCB might therefore be acceptable as an alternate SCT source for HLH patients, although the optimal conditioning remains to be determined.
No preview · Article · Oct 2009 · Pediatric Blood & Cancer
[Show abstract][Hide abstract] ABSTRACT: Viral resistance to antiviral drugs can cause serious complications in immunosuppressed patients. We isolated from an allogeneic stem cell transplant (SCT) recipient an antiviral-resistant human herpesvirus 6 (HHV-6) strain with mutations that caused amino acid substitutions.
To study the impact of mutations in the U38 and U69 genes of the ganciclovir (GCV)-resistant HHV-6 strain associated with the death of the SCT recipient.
Viruses were obtained from blood taken during symptomatic disease. Mutations in the genes for U69 protein kinase and U38 DNA polymerase were analyzed and the effects of the U69 mutations on GCV resistance were assayed using a recombinant baculovirus system.
Increasing HHV-6 antigenemia occurred after 2-3 months of preemptive GCV therapy, followed by symptomatic HHV-6 disease that ended in fatal fungus-related septic shock. The HHV-6 strain isolated from the patient was 100-fold more resistant to GCV than was a wild-type strain. New mutations were found in HHV-6 genes U38 (P462S and A565V) and U69 (L202I and L213I). The mutation of U38 P462S corresponds to a mutation in the UL54 gene (P522S) of a GCV-resistant HCMV. The U69 mutations did not alter GCV sensitivity in baculovirus GCV-resistant assay system.
Drug-resistant mutations arising during preemptive therapy may complicate post-transplant HHV-6 disease in SCT recipients. The increased copy number during GCV treatment of this new GCV-resistant HHV-6 strain correlated with mutations in the U69 and U38 genes. Since the kinase mutation did not alter sensitivity to GCV when tested in the in vitro system, it is likely that the substitutions in the polymerase related to GCV resistance.
No preview · Article · Nov 2008 · Journal of Clinical Virology
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to clarify the feasibility of a novel treatment strategy consisting of postponed primary surgery till the end of systemic chemotherapy including HDC without interruption by local therapy for neuroblastoma patients at a high risk for relapse. After induction chemotherapy, patients received double conditioning HDC consisting of thiotepa and melphalan. Radical surgery was applied to local lesions. Irradiation was not applied to any lesions. Eleven consecutive pediatric neuroblastoma patients were treated according to this strategy. Seven of 11 patients remained in complete remission for 21-171 months. This treatment strategy seems feasible and a further study is warranted.
No preview · Article · Jul 2008 · Pediatric Hematology and Oncology
[Show abstract][Hide abstract] ABSTRACT: We have little information on chronic graft-versus-host disease (GVHD) after cord blood transplantation (CBT). We investigated its clinical features in 1072 Japanese patients with hematologic malignancies who received a transplant through the Japan Cord Blood Bank Network. The primary end point was to investigate the incidence of any chronic GVHD. Median age of the patients was 33 years (range, 0-79 years). The cumulative incidence of chronic GVHD 2 years after transplantation was 28%. Chronic GVHD was fatal in 29 patients. Multivariate analysis demonstrated that development of chronic GVHD was favorably associated with both overall survival and event-free survival. Multivariate analysis identified risk factors of chronic GVHD: higher patient body weight, higher number of mismatched antigens for GVHD direction, myeloablative preparative regimen, use of mycophenolate mofetil in GVHD prophylaxis, and development of grades II to IV acute GVHD. Although chronic GVHD is a significant problem after CBT, it is associated with improved survival, perhaps due to graft-versus-malignancy effects.
[Show abstract][Hide abstract] ABSTRACT: A pilot study was undertaken using a myeloablative conditioning with fludarabine, busulfan, and melphalan to improve the outcome of HSCT in 10 children, aged six months to six yr, with JMML. All patients were conditioned with oral busulfan (560 mg/m(2)), fludarabine (120 mg/m(2)), and melphalan (180-210 mg/m(2)) prior to HSCT, and received stem cells from bone marrow in seven cases, and from cord blood in three cases. Engraftment was documented in eight patients, whereas graft failure occurred in two, one of whom had received HLA-mismatched cord blood and other had received bone marrow from HLA-mismatched mother. Three patients, including two in who graft failure had occurred, relapsed. Five patients developed acute GVHD and two developed chronic GVHD. Seven patients are alive and in remission 27-69 months after transplantation. Thus, our study showed that HSCT following conditioning with fludarabine, busulfan, and melphalan was well tolerated and appeared to be effective for JMML.
No preview · Article · May 2008 · Pediatric Transplantation
[Show abstract][Hide abstract] ABSTRACT: Blasts from eight cases with acute megakaryoblastic leukaemia (AMKL) and seven with transient abnormal myelopoiesis in Down's syndrome (TAM) were investigated to clarify their phenotypic characteristics. CD41 and CD7 were the most frequently expressed in both disorders. CD41 was positive in six TAM and five AMKL cases, and CD7 was positive in five TAM and five AMKL cases, respectively. CD33 was detected in four TAM and five AMKL cases. Other myeloid-lineage associated antigens such as CD13 and CD11b could not be found in TAM but were expressed in five AMKL cases. Interestingly, CD56, a neural adhesion molecule, was expressed in three of four TAM and one of five AMKL cases. Cytoplasmic CD3 antigen was also noted in three of five examined cases.A short-term culture study was conducted on blasts from two TAM cases and five AMKL cases. In two cases in which CD41 was not expressed before culture, the expression of CD41 was enhanced after culture with or without 12–0-tetradecanoyl-phorbol-13-acetate (TPA). The expression of CD7 remarkably was depressed, while that of CD13 was enhanced after culture with TPA.These findings suggest that blasts of TAM and AMKL originate from very immature cells and represent a mixed phenotype. In the present study, distinction of pheno-typical differences between blast in TAM and AMKL was not possible.
No preview · Article · Mar 2008 · British Journal of Haematology
[Show abstract][Hide abstract] ABSTRACT: We analyzed the outcomes of 44 children with hepatitis associated aplastic anemia (HAA) who received immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and cyclosporine (CsA). Fourteen (31.8%) patients achieved complete response and 17 (38.6%) achieved partial response, for an overall response rate of 70.4% after 6 months. Seven non-responders received bone marrow transplantation from an HLA-matched unrelated donor and 6 out of 7 are alive. The probability of overall survival at 10 years was 88.3+/-4.9%, which supports the role of IST with ATG and CsA as treatment of choice for children with HAA without an HLA identical sibling donor.
[Show abstract][Hide abstract] ABSTRACT: Non-T-cell-depleted HLA-haploidentical hematopoietic stem cell transplantation (SCT) from family members has been reported, but its effectiveness and safety are not fully known. In this study, we examined the outcomes of 83 children and adolescents with nonmalignant (n = 11) or malignant (n = 72) disorders who underwent SCT mismatched at 2 or 3 HLA loci, either from the mother (n = 56), a noninherited maternal antigen (NIMA)-mismatched sibling (n = 14), or the father/a noninherited paternal antigen (NIPA)-mismatched sibling (n = 13). Engraftment was satisfactory. Severe (grade III-IV) acute graft-versushost disease (GVHD) was noted only in malignant disease, with an incidence of 21 of 64 evaluable patients. GVHD prophylaxis with a combination of tacrolimus and methotrexate was significantly associated with a lower risk of severe acute GVHD, compared with other types of prophylaxis (P = .04). Nine of 11 patients with nonmalignant disease and 29 of 72 patients with malignant disease were alive at a median follow-up of 26 months (range, 4-57 months). Outcomes were not significantly different among the 3 donor groups (mother versus NIMA-mismatched sibling versus father/NIPA-mismatched sibling) for the malignancy disorders. Our results indicate that non-T-cell-depleted HLA-haploidentical SCT may be feasible, with appropriate GVHD prophylaxis, for young recipients who lack immediate access to a conventional stem cell source.
No preview · Article · May 2007 · International Journal of Hematology
[Show abstract][Hide abstract] ABSTRACT: Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive disorder characterized by exocrine pancreatic insufficiency, bone marrow dysfunction, and skeletal abnormalities. SBDS was identified as a causative gene for SDS in 2003, and genetic analyses of SDS have been performed. We performed genetic analysis of 13 Japanese patients with presumed SDS and found that 10 of them had SBDS mutations. Most patients had recurrent mutations (181-184TA-->CT and 258+2T-->C); however, 2 patients had unique mutations (259-1G-->A and 428C-->G). Although genetic analysis is useful for definitive diagnosis and for genetic counseling of SDS patients and families, SDS appears to be a genetically heterogeneous disorder. In addition, presumed SDS patients without SBDS mutations may be included in other disorders.
No preview · Article · Jul 2006 · International Journal of Hematology
[Show abstract][Hide abstract] ABSTRACT: Most cases of nephrotic syndrome following stem cell transplantation (SCT) occur 6 months after SCT. The patients are treated with immunosuppressive therapies; however, in some cases treatment is not effective. We used enalapril, an angiotensin-converting enzyme inhibitor (ACEI) and candesartan, an angiotensin II receptor blocker (ARB), for the control of proteinuria in a case of immunosuppressive treatment (IST)-resistant nephrotic syndrome. A 15-year-old boy with acute lymphoblastic leukemia underwent allogeneic peripheral blood SCT from a completely HLA-matched sibling after completion of a conditioning regimen composed of 12-Gy doses of total-body irradiation, 600 mg/m2 thiotepa, and 140 mg/m2 melphalan. Twenty-eight months after SCT, minimal-change nephrotic syndrome was diagnosed on the basis of biopsy findings. Although neither cyclosporine (trough level, 100-150 ng/mL) nor corticosteroid was effective, proteinuria disappeared 2 months after the beginning of treatment with tacrolimus (trough level, 13-20 ng/mL), and remission was maintained for 23 months. Nephrotic syndrome recurred, however, and was resistant to tacrolimus. Findings at the second renal biopsy revealed membranous nephropathy. An ARB (candesartan, 4 mg/ day) in combination with an ACEI (enalapril, 5 mg/day) was started. Proteinuria improved within 2 weeks. We suggest that ARB combined with ACEI can be used to control proteinuria in patients with IST-resistant nephrotic syndrome after SCT.
No preview · Article · Jul 2006 · International Journal of Hematology
[Show abstract][Hide abstract] ABSTRACT: Bone marrow (BM) stroma provides the microenvironment required for long-term hematopoiesis, and this is supported by direct interaction between stromal cells and hematopoietic cells, mediated by adhesion molecules, and through cytokine releases from the BM stroma. In a previous study, we demonstrated that hepatocyte growth factor (HGF) is one of the cytokines constitutively produced from BM stromal cells, promoting hematopoiesis mainly in an indirect way. We also showed that stromal cells themselves express HGF receptor c-MET. It was therefore postulated that HGF exerts its effect on hematopoiesis and maintenance of the hematopoietic microenvironment in a paracrine and autocrine manner.
The effect of HGF on stromal cells was analyzed by neutralizing intrinsic HGF.
Addition of neutralizing anti-HGF antibody inhibited the ability of BM stromal cells to support colony formation from CD34(+) cells and reduced production of significant cytokines from stromal cells, interleukin-11 (IL-11), stromal cell-derived factor-1 alpha (SDF-1 alpha), and to a lesser extent, stem cell factor (SCF). Furthermore, this neutralizing antibody reduced proliferation of stromal cells and inhibited adhesion of stromal cells to collagen type IV and fibronectin. Inhibition of adhesion to fibronectin was mediated by inhibition of alpha(5)beta(1)-integrin.
These findings indicate that HGF constitutively produced from BM stromal cells is an autocrine regulator, which is able to maintain the hematopoietic microenvironment through stimulating proliferation and adhesion to the extracellular matrix and promoting hematopoiesis through inducing constitutive production of IL-11, SDF-1 alpha, and SCF by stromal cells themselves.
No preview · Article · Nov 2004 · Experimental Hematology
[Show abstract][Hide abstract] ABSTRACT: Dendritic cells (DCs) initiate and direct immune responses. Recent studies have defined different DC populations, therefore we undertook this study comparing 2 types of myeloid DCs: blood CD11c(+) DCs and in vitro monocyte-derived DCs (Mo-DCs), which are both candidates as cellular adjuvants for cancer immunotherapy. Blood CD11c(+) DCs were prepared by cell sorting from peripheral blood mononuclear cells cultured overnight in RPMI 1640 medium supplemented with autologous or pooled AB serum. Mo-DCs were prepared in the same medium using granulocyte macrophage-colony-stimulating factor (GM-CSF)/interleukin 4 (IL-4) and differentiated/activated with lipopolysaccharide or monocyte-conditioned medium (ActMo-DCs). Morphologically, differences between the DC preparations were noted both at a light and and electron microscopic level. Blood CD11c(+) DCs expressed similar levels of HLA-DR, CD40, CD86, and CD83 as Mo-DCs. CD209 was present on Mo-DCs but not on blood CD11c(+) DCs. Blood CD11c(+) DCs generated a lower proliferative mixed leukocyte response (MLR) than Mo-DCs. Blood CD11c(+) DCs loaded with 0.1 microg/mL tetanus toxoid (TT)-generated greater T lymphocyte proliferative responses than did Mo-DCs or ActMo-DCs, but when loaded with higher TT concentrations no difference in T lymphocyte proliferative response was observed. Keyhole limpet hemocyanin (KLH)-loaded blood CD11c(+) DCs generated greater T lymphocyte proliferative responses than Mo-DCs or ActMo-DCs. Allogeneic MLR- or KLH-specific responses induced by blood CD11c(+) DCs generated more Th1 effectors than the responses induced by Mo-DCs or ActMo-DCs. These data establish several differences in the properties of blood CD11c(+) DCs, Mo-DCs, and ActMo-DCs, which suggest that blood DCs merit further consideration as DC preparations for clinical programs are evolved.