This study prospectively evaluated the rate of biologic response to desmopressin (DDAVP) in 66 patients with type 1 or 2 von Willebrand disease (VWD), each of whom had, on the basis of available records, a clinically significant bleeding history and at least one of the following laboratory abnormalities: bleeding time (BT) longer than 15 minutes, ristocetin cofactor activity (VWF:RCo) less than 10 IU/dL, factor VIII coagulant activity (FVIII:C) less than 20 IU/dL (severe VWD). Before the study, responsive patients were defined as those who, 2 hours after infusion of 0.3 microg/kg DDAVP, had increased baseline values of VWF:RCo and FVIII:C by at least 3-fold and achieved levels of at least 30 IU/dL for both and a BT of 12 minutes or less. The rate of biologic response varied according to VWD types and was higher in type 1 (7 of 26, 27%) than in type 2 (7 of 40, 18%) (type 2A [1 of 15, 7%], type 2M [3 of 21, 14%], type 2N [3 of 4, 75%]). Mutations in the VWF gene were previously known or newly identified in most patients with types 2A (n = 15 of 15), 2M (n = 15 of 21), and 2N (n = 4 of 4), but in none of those with type 1 VWD. Genotype provided more information than phenotype in predicting individual responses to DDAVP only in patients with 2A and 2N VWD. This prospective study showed that the rate of biologic response to DDAVP is relatively low not only in type 2 but also in type 1 VWD when uniform and stringent criteria for patient selection and responsiveness are applied.

Transplantation-associated bone loss is a well-known phenomenon, however, effects of hematopoietic stem cell transplantation are insufficiently characterized. We conducted a prospective, unicentric, long-term follow-up in 280 patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Bone mineral density (BMD) was measured before transplantation and then yearly for at least 4 years. Patients received vitamin D plus calcium until steroid withdrawal. Mean baseline BMD was normal. We demonstrated significant bone loss with nadir BMD at month 6 for the spine and at month 24 for total body and femoral neck. Average annual bone loss was 0.6% for spine, 0.4% for total body, 2.3% for femoral neck, and 3.5% for Ward triangle. While spine and total body BMD returned to baseline, bone loss at femoral neck sites was attenuated, but BMD did not return to baseline until month 48 (P <.0001 for femoral neck and Ward triangle). Univariate factor analysis of 15 potential risk factors for rapid bone loss revealed a positive correlation of bone loss with steroid and cyclosporine A use, baseline BMD, and loss of muscle mass (overwhelming power of steroid use in multifactor analysis). Such rapid BMD changes probably increase fracture risk consecutive to irreversible microarchitectural changes even if osteodensitometry shows long-term recovery.

Hydroxyurea improves hematologic parameters for children with sickle cell disease (SCD), but its long-term efficacy at maximum tolerated dose (MTD) has not been determined. Between 1995 and 2002, hydroxyurea therapy was initiated for 122 pediatric patients with SCD including 106 with homozygous sickle cell anemia (HbSS), 7 with sickle hemoglobin C (HbSC), 7 with sickle/beta-thalassemia (HbS/ beta-thalassemia [6 HbS/beta0, 1 HbS/beta+]), and 2 with sickle hemoglobin OArab (HbS/OArab). Median age at initiation of therapy was 11.1 years. Hydroxyurea was escalated to MTD, with an average dose of 25.4 +/- 5.4 mg/kg per day; the average duration of hydroxyurea therapy has been 45 +/- 24 months (range, 6-101 months). Hydroxyurea was discontinued for 15 (12%) children with poor compliance. Mild transient neutropenia occurred, but no hepatic or renal toxicity was noted. Hydroxyurea therapy led to significant increases in hemoglobin level, mean corpuscular volume, and fetal hemoglobin (HbF) level, whereas significant decreases occurred in reticulocyte, white blood cell, and platelet counts and serum bilirubin levels. Children with variant SCD genotypes also had hematologic responses to hydroxyurea. HbF induction has been sustained for up to 8 years without adverse effects on growth or increased numbers of acquired DNA mutations. Long-term hydroxyurea therapy at MTD is well tolerated by pediatric patients with SCD and has sustained hematologic efficacy with apparent long-term safety.

Decitabine (5-aza-2'-deoxycytidine) inhibits DNA methylation and has dual effects on neoplastic cells, including the reactivation of silenced genes and differentiation at low doses and cytotoxicity at high doses. We evaluated, in a phase 1 study, low-dose prolonged exposure schedules of decitabine in relapsed/refractory leukemias. Patient cohorts received decitabine at 5, 10, 15, or 20 mg/m2 intravenously over one hour daily, 5 days a week for 2 consecutive weeks, doses 5- to approximately 30-fold lower than the maximum tolerated dose (MTD). There were 2 groups that also received 15 mg/m2 daily for 15 or 20 days. A total of 50 patients were treated (44 with acute myelogenous leukemia [AML]/myelodysplasia [MDS], 5 with chronic myelogenous leukemia [CML], and 1 with acute lymphocytic leukemia [ALL]), and the drug was well tolerated at all dose levels, with myelosuppression being the major side effect. Responses were seen at all dose levels. However, the dose of 15 mg/m2 for 10 days appeared to induce the most responses (11 of 17 or 65%), with fewer responses seen when the dose was escalated or prolonged (2 of 19 or 11%). There was no correlation between P15 methylation at baseline or after therapy and response to decitabine. We conclude that decitabine is effective in myeloid malignancies, and low doses are as or more effective than higher doses.

Data on the application of donor lymphocyte infusions (DLIs) following reduced-intensity transplantation (RIT) remain limited. Persistence of host antigen-presenting cells might increase the efficacy or toxicity of cellular immunotherapies. We report the results of dose-escalating DLIs in 46 patients undergoing RIT, who received a total of 109 infusions to treat mixed chimerism or residual or progressive disease. Diagnoses were myeloma (n = 19), Hodgkin lymphoma (n = 13), non-Hodgkin lymphoma (n = 10), and other (n = 4). Thirty-two had an HLA-matched family donor and 14 an unrelated donor. Grades II to IV graft-versus-host disease (GVHD) occurred in 5 sibling and 7 unrelated donor recipients. GVHD was more common (P =.002), occurred at lower T-cell doses, and was more severe in the unrelated donor cohort. Conversion from mixed to multilineage full donor chimerism occurred in 30 of 35 evaluable patients. Presence of mixed chimerism in the granulocyte lineage at the time of DLI did not predict for chimerism response or GVHD. Disease responses occurred in 63% of patients with myeloma and 70% of those with Hodgkin lymphoma and were not predicted by changes in chimerism. These data support the presence of clinically relevant graft-versus-Hodgkin activity and indicate that DLI may be associated with a significantly increased toxicity in unrelated compared to sibling donor transplant recipients receiving identical treatment protocols.

Imatinib has pronounced but brief antileukemic activity in advanced Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL). We assessed the prognostic impact of pretreatment disease features and the early bone marrow (BM) response in 68 consecutive patients with Ph(+)ALL receiving imatinib salvage therapy. A complete hematologic or marrow response was achieved by 92% of patients with BM blasts below 5% on day 14, whereas 62.5% of patients with more than 5% BM blasts on day 14 were nonresponders. Similarly, time to progression (TTP) was superior in patients with a good day 14 response (5.2 versus 0.9 months; P <.0001). Prior complete remission of less than 6 months, white blood cell count of more than 10 x 10(9)/L, circulating peripheral blood blasts at diagnosis, additional Philadelphia chromosomes, or at least 2 Bcr-Abl fusion signals were associated with significantly inferior remission rate and response duration. In patients without poor prognostic features, single-agent imatinib may be appropriate before transplant salvage therapy. Conversely, patients with clinically or cytogenetically defined poor-risk features are candidates for trials of upfront imatinib in combination with other agents.

All-trans-retinoic acid (ATRA) increases the efficacy of chemotherapy when used for induction and maintenance treatment of acute promyelocytic leukemia (APL), but its role in consolidation is unknown. Since November 1996, 426 patients with newly diagnosed APL have received induction therapy with ATRA and idarubicin. Before November 1999 (LPA96 study), consolidation therapy consisted of 3 courses of anthracycline monochemotherapy. After November 1999 (LPA99 study), patients with intermediate and high risks of relapse received consolidation therapy with ATRA and increased doses of anthracyclines. Of the 384 patients who achieved complete remission (90%), 382 proceeded to consolidation therapy. Seven patients died in remission (1.8%). The 3-year cumulative incidence of relapse for patients in the LPA96 and LPA99 studies was 17.2% and 7.5%, respectively (P =.008). Patients treated with ATRA in consolidation therapy showed an overall reduction in the relapse rate from 20.1% to 8.7% (P =.004). In intermediate-risk patients the rate decreased from 14.0% to 2.5% (P =.006). This improved antileukemic efficacy also translated into significantly better disease-free and overall survival. A risk-adapted strategy combining anthracycline monochemotherapy and ATRA for induction and consolidation therapy of newly diagnosed APL results in improved antileukemic efficacy and a high degree of compliance.

In follicular lymphoma (FL), genomic polymorphisms corresponding to the expression of valine (V) or phenylalanine (F) at amino acid 158 of Fc gamma RIIIa alter the binding affinity of immunoglobulin G1 (IgG1) to the receptor and have been associated with varied responses to rituximab. We examined Fc gamma RIIIa polymorphisms of 30 CLL patients with the phenotypes V/V (n = 6), V/F (n = 12), and F/F (n = 12) treated with thrice-weekly rituximab (375 mg/m(2)) for 4 weeks to correlate polymorphism type with infusion toxicity and response. Infusion toxicity (grade 3 or greater or hypoxia/hypotension requiring transient cessation of therapy) was observed equally among the groups (V/V, 50%; V/F, 33%; F/F, 41.6%; P =.78). The response to rituximab was also similar among the different polymorphism phenotypes (V/V, 33%; V/F, 41.6%; F/F, 50%). These data suggest that Fc gamma RIIIa polymorphisms are not predictive of response in CLL and that, unlike the case with FL, mechanisms of tumor clearance other than antibody-dependent cellular cytotoxicity may be more important.

The ability of donor lymphocyte infusions (DLIs) to induce complete responses (CRs) in patients with relapsed myeloma after allogeneic bone marrow transplantation (BMT) provides clear evidence of an effective graft-versus-myeloma (GVM) response. To identify target antigens of the GVM response, we screened a myeloma cDNA expression library with post-DLI serum from 4 patients with myeloma who achieved CR after DLI and 1 patient who was in CR before DLI. We identified a panel of 13 gene products reactive with post-DLI serum but negative with pre-DLI and pre-BMT serum. Antibodies to these proteins were not detected in the sera of 10 patients who underwent allogeneic BMT without DLI and 5 patients with acute graft-versus-host disease (GVHD). Minimal reactivity with these proteins was detected in the sera of 20 healthy donors and 20 patients with chronic GVHD. In contrast, 5 of these proteins were recognized by more than 1 myeloma DLI responder. Testing of serial serum samples showed an association between antibody response and time of best response after DLI. The expression of these genes was evaluated in primary myeloma cells and in normal plasma cells. This study demonstrates that the GVM response is associated with antibody responses to highly expressed myeloma-associated antigens.

A plausible mechanism to explain thrombotic risk differences associated with the use of second- and third-generation oral contraceptives (OCs), particularly in carriers of factor V(Leiden), is still lacking. In a double-blind trial, 51 women without and 35 women with factor V(Leiden) were randomized to either a second- (30 microg ethinylestradiol/150 microg levonorgestrel) or third- (30 microg ethinylestradiol/150 microg desogestrel) generation OC. After 2 cycles of use and a wash-out of 2 cycles, the participants continued with the corresponding progestagen-only preparation. Hemostatic variables that probe the activity of the anticoagulant protein C system were determined. Compared with levonorgestrel, desogestrel-containing OCs significantly decreased protein S and increased activated protein C (APC) resistance in both groups. OCs with desogestrel had the most pronounced effects in carriers of factor V(Leiden). Progestagen-only preparations caused changes of anticoagulant parameters opposite to those of combined OCs, which in a number of cases were more pronounced with levonorgestrel. Our data show that progestagens in combined OCs counteract the thrombotic effect of the estrogen component. The higher thrombotic risk associated with third-generation OCs compared with second-generation OCs may be explained by the fact that desogestrel appeared less antithrombotic than levonorgestrel, especially in women with factor V(Leiden).

Despite progress in leukemia therapy, most children who experience relapse have a dismal prognosis. New, effective approaches are needed. We conducted a phase 1 study of a novel nucleoside analog, clofarabine, in pediatric patients with refractory and relapsed leukemia. Clofarabine was infused intravenously over 1 hour each day for 5 days. Six dose levels, between 11.25 and 70 mg/m(2) per day for 5 days, were studied in 25 patients. A modified 3 + 3 phase 1 design was followed with 30% dose escalation until the dose-limiting toxicity (DLT) was defined. The maximum tolerated dose (MTD) was 52 mg/m(2) per day for 5 days. At the end of infusion at MTD, clofarabine triphosphate levels in leukemia blasts varied between 6 microM and 19 microM, which resulted in complete and sustained inhibition of DNA synthesis. The DLT was reversible hepatotoxicity and skin rash at 70 mg/m(2) per day for 5 days. Twenty-five patients were treated. Five patients achieved complete remission (CR), and 3 achieved partial remission (PR), for an overall response rate of 32%. Clofarabine is well tolerated and shows significant antileukemic activity in heavily pretreated children. Multicenter phase 2 trials in pediatric acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) are ongoing.

Blockade of the CD40/CD154 signal is a potential immunomodulatory strategy for T-cell-mediated diseases. As a part of a phase 1, multicenter, dose-escalating trial of humanized monoclonal antibody to CD154 (IDEC-131/E6040) in patients with refractory immune thrombocytopenic purpura (ITP), the autoimmune response to glycoprotein IIb/IIIa (GPIIb/IIIa) was evaluated at successive time points. Five patients each were given a single infusion of 1, 2, 5, or 10 mg/kg IDEC-131/E6040 and followed for 3 months. All adverse events were mild, and there were no severe infections or thromboembolic events. No increase in platelet count was observed in patients treated at 1, 2, or 5 mg/kg, but an increase was observed in 3 patients treated at 10 mg/kg. In only the patients treated at 5 or 10 mg/kg, the frequency of B cells producing anti-GPIIb/IIIa antibodies, GPIIb/IIIa-induced T-cell proliferation, and anti-GPIIb/IIIa antibody production by antigen-dependent T-B-cell collaboration were all suppressed in parallel after the treatment, with a slow return to baseline. In contrast, T-cell response to an irrelevant antigen was not affected. These findings suggest that CD40/CD154 blockade therapy is potentially effective for refractory ITP, through selective suppression of autoreactive T and B cells to platelet antigens.

Imatinib mesylate, an inhibitor of the Bcr-Abl tyrosine kinase, has modest activity in refractory/relapsed Philadelphia chromosome (Ph)-positive acute lymphocytic leukemia (ALL). Use of concurrent chemotherapy and imatinib mesylate in newly diagnosed Ph-positive ALL was explored. There were 20 patients who received hyper-CVAD (cyclophosphamide, vincristine, Adriamycin, and dexamethasone) and imatinib mesylate followed by imatinib mesylate-based consolidation/maintenance therapy. Of these patients, 11 had de novo disease, 4 were primary failures after induction (without imatinib mesylate), and 5 were in complete remission (CR) after induction (without imatinib mesylate). All 15 patients treated for active disease achieved CR. Within a median of 3.5 months in first CR, 10 patients underwent allogeneic stem cell transplantation (SCT). One patient relapsed after matched related SCT. The other 9 patients remained alive in CR with median follow-up of 12 months after SCT (range, 1+ to 17+ months). Among 10 patients ineligible for (no donor or older age) or refusing allogeneic SCT, 1 patient relapsed after one year. There were 5 patients who remained alive in continuous CR for a median of 20 months (range, 4+ to 24+ months), with 2 older patients dying in CR at 15 and 16 months of comorbid conditions. Molecular CRs were achieved in both groups (SCT or no SCT). Outcome with hyper-CVAD and imatinib mesylate appears better than with prior regimens; continued accrual and longer follow-up of the current cohort is needed.

It has been proposed that paroxysmal nocturnal hemoglobinuria (PNH) cells may proliferate through their intrinsic resistance to immune attack. To evaluate this hypothesis, we examined the impact of alloimmune pressure on PNH and normal cells in the clinical setting of nonmyeloablative allogeneic hematopoietic cell transplantation (HCT). Five patients with severe PNH underwent HCT from an HLA-matched family donor after conditioning with cyclophosphamide and fludarabine. PNH neutrophils (CD15(+)/CD66b(-)/CD16(-)) were detected in all patients at engraftment, but they subsequently declined to undetectable levels in all cases by 4 months after transplantation. To test for differences in susceptibility to immune pressure, minor histocompatibility antigen (mHa)-specific T-cell lines or clones were targeted against glycosylphosphatidylinositol (GPI)-negative and GPI-positive monocyte and B-cell fractions purified by flow cytometry sorting. Equivalent amounts of interferon-gamma (IFN-gamma) were secreted following coculture with GPI-negative and GPI-positive targets. Furthermore, mHa-specific T-cell lines and CD8(+) T-cell clones showed similar cytotoxicity against both GPI-positive and GPI-negative B cells. Presently, all 5 patients survive without evidence of PNH 5 to 39 months after transplantation. These in vitro and in vivo studies show PNH cells can be immunologically eradicated following nonmyeloablative HCT. Relative to normal cells, no evidence for a decreased sensitivity of PNH cells to T-cell-mediated immunity was observed.

Prophylactic fluconazole prevents candidiasis; however, this drug has no activity against molds. We performed a randomized trial to determine whether prophylactic itraconazole prevents invasive mold infections (IMIs). A total of 304 patients receiving allogeneic stem cell transplants (SCT) were randomized to receive fluconazole (400 mg/d) or itraconazole (oral solution 2.5 mg/kg 3 times daily, or intravenous 200 mg daily) for 180 days after SC transplantation, or until 4 weeks after discontinuation of graft-versus-host disease (GVHD) therapy. Proven or probable invasive fungal infections (IFI) were evaluated by intent-to-treat and "on-treatment" analyses. More patients in the itraconazole arm developed hepatotoxicities, and more patients were discontinued from itraconazole because of toxicities or gastrointestinal (GI) intolerance (36% versus 16%, P <.001). Intent-to-treat analysis demonstrated no difference in the incidence of IFI during the intended study period (fluconazole 16% versus itraconazole 13%, P =.46); however, fewer patients in the itraconazole arm developed IFI on treatment (fluconazole 15% versus itraconazole 7%, P =.03). Itraconazole provided better protection against IMI (fluconazole 12% versus itraconazole 5%, P =.03), but similar protection against candidiasis (3% versus 2%, P =.69). There was no difference in overall or fungal-free survival. Itraconazole appears to prevent IMI in the subset of patients who tolerate the drug; however, toxicities and poor tolerability limit its success as prophylactic therapy.

This study retrospectively analyzed data from 446 patients given hematopoietic cell transplants from HLA-matched related or unrelated donors after conditioning with 2 Gy total body irradiation with or without fludarabine and postgrafting immunosuppression with mycophenolate mofetil and cyclosporine following grafting. Fifty-three of 446 patients received donor lymphocyte infusion (DLI) with a median CD3 dose of 1 x 10(7) cells/kg. Their diagnoses included myelodysplastic syndrome (n = 10), acute leukemia (n = 10), chronic leukemia (n = 11), multiple myeloma (n = 9), lymphoma (n = 9), and solid tumors (n = 4). Patients received DLI for persistent disease (n = 8), disease relapse (n = 17), progressive disease (n = 12), low donor chimerism with disease (n = 11), or low chimerism with disease remission (n = 5). Seventeen of the 53 patients (32%) are alive with a median follow-up of 30 months; 5 are in complete remission (CR), 2 are in partial remission (PR), and 10 have stable or progressive disease. Nine of 53 patients (17%) developed grades II to IV acute graft-versus-host disease. Of 48 patients receiving DLI for treatment of disease, 7 achieved CR and 5 PR, with an overall response rate of 25%. Six of 16 patients who received DLI for chimerism had increases in donor chimerism leading to sustained engraftment, whereas 10 eventually rejected their grafts. In conclusion, DLI is a potential treatment strategy, with acceptable toxicity, for patients with persistent, relapsed, or progressive disease after nonmyeloablative hematopoietic cell transplantation.

Human Valpha24+Vbeta11+ natural killer T (NKT) cells are a distinct CD1d-restricted lymphoid subset specifically and potently activated by alpha-galactosylceramide (alpha-GalCer) (KRN7000) presented by CD1d on antigen-presenting cells. Preclinical models show that activation of Valpha24+Vbeta11+ NKT cells induces effective antitumor immune responses and potentially important secondary immune effects, including activation of conventional T cells and NK cells. We describe the first clinical trial of cancer immune therapy with alpha-GalCer-pulsed CD1d-expressing dendritic cells. The results show that this therapy has substantial, rapid, and highly reproducible specific effects on Valpha24+Vbeta11+ NKT cells and provide the first human in vivo evidence that Valpha24+Vbeta11+ NKT cell stimulation leads to activation of both innate and acquired immunity, resulting in modulation of NK, T-, and B-cell numbers and increased serum interferon-gamma. We present the first clinical evidence that Valpha24+Vbeta11+ NKT cell memory produces faster, more vigorous secondary immune responses by innate and acquired immunity upon restimulation.

We followed 141 patients treated with imatinib mesylate (> 300 mg) for chronicphase chronic myelogenous leukemia (CML) following failure of treatment with interferon. During 12 months from the start of imatinib mesylate treatment, 96.5% achieved a complete hematologic response, 47.0% achieved a major cytogenetic response, and 32.4% achieved a complete cytogenetic response. The proportion of patients with hematologic relapse was 10.9% at 12 months and 14.6% at 18 months. In a univariate Cox regression analysis, the only pretreatment characteristics that correlated with an increased risk of hematologic relapse were hemoglobin level less than 120 g/L (12 g/dL) (P =.02), increased bands in the peripheral blood (P =.01), and clonal evolution (P <.0001). In a multivariate analysis, an elevated platelet count (P =.03) and clonal evolution (P <.0001) were the only significant factors for hematologic relapse. During treatment, the absence of a major cytogenetic response within the first 6 months also significantly correlated with relapse (P =.03). Notably, patients failing to achieve a major cytogenetic response by 6 months had a significantly higher rate of hematologic relapse (27%) compared with those who achieved a major cytogenetic response by 6 months (3%), and patients with clonal evolution had a significantly higher risk of hematologic relapse (50%) than those without clonal evolution (9%).

The optimal induction for older adults with acute myeloid leukemia (AML) is unknown. Several anthracyclines have been proposed, but the data remain equivocal. Additionally, few prospective trials of priming with hematopoietic growth factors to cycle leukemia cells prior to induction chemotherapy have been conducted. Three hundred and sixty-two older adults with previously untreated AML were randomized to either daunorubicin, idarubicin or mitoxantrone with a standard dose of cytarabine as induction therapy. In addition, 245 patients were also randomized to receive granulocyte-macrophage colony-stimulating factor (GM-CSF) or placebo beginning 2 days prior to induction chemotherapy and continuing until marrow aplasia. No difference was observed in the disease-free overall survival or in toxicity among patients receiving any of the 3 induction regimens or among those receiving growth factor or placebo for priming. However, the complete remission rate for the first 113 analyzable patients, who did not participate in the priming study and started induction therapy 3 to 5 days earlier than those who did, was significantly higher (50% versus 38%; P =.03). None of the anthracyclines is associated with improved outcome in older adults. Priming with hematopoietic growth factor did not improve response when compared with placebo. Furthermore, delaying induction therapy in older adults may lead to a lower complete remission rate.

A tumor-specific, bcr-abl-derived fusion peptide vaccine can be safely administered to patients with chronic myelogenous leukemia (CML) and can elicit a bcr-abl peptide-specific T-cell immune response. In the present phase 2 trial, 14 patients with CML in chronic phase were vaccinated with 6 fusion peptides mixed with Quillaja saponaria (QS-21). No significant toxic effects were observed. In 14 of 14 patients, delayed-type hypersensitivity (DTH) and/or CD4 proliferative responses developed after beginning vaccinations, and 11 of 14 patients showed interferon-gamma (IFN-gamma) release by CD4 enzyme-linked immunospot (ELISPOT) at one or more time points. These responses were CD4(+)CD45RO(+). A peptide-specific CD8(+) interferon-gamma ELISPOT was found in 4 patients. Four patients in hematologic remission had a decrease in Philadelphia chromosome (Ph) percentage (3 concurrently receiving interferon-alpha and 1 on imatinib mesylate), and 3 patients in molecular relapse after allogenic transplantation became transiently polymerase chain reaction (PCR) negative after vaccination; 2 of these patients received concurrent donor lymphocyte infusion (DLI). All 5 patients on IFN-alpha ultimately reached a complete cytogenetic remission. In conclusion, a tumor-specific bcr-abl breakpoint peptide-derived vaccine can be safely administered and can reliably elicit measurable peptide-specific CD4 immune responses, including in patients after bone marrow transplantation, on interferon, or on imatinib mesylate. A relationship between the clinical responses and vaccination cannot be determined from this trial.