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Yoichi Takaue

Publications and source records attributed to Yoichi Takaue.

At least 19 recordsLinked to original sources
PubMed2006

Monitoring of WT1-specific cytotoxic T lymphocytes after allogeneic hematopoietic stem cell transplantation.

Donor-derived cytotoxic T lymphocytes (CTL) that respond to tumor antigens emerge after hematopoietic stem cell transplantation (HSCT), particularly in association with the status of immune recovery. To analyze the frequency of CTL against PR1, PRAME and WT1 after HSCT, a tetramer-based analysis was performed in 97 samples taken from 35 patients (9 AML, 11 MDS, 2 CML, 4 ALL, 7 lymphoma and 2 renal cell carcinoma [RCC]) with the HLA-A02 phenotype. Regarding PR1, only 1 sample showed the presence of tetramer-positive cells (0.04%/lymphocyte). Similarly, in PRAME, only 10 of 97 samples were sporadically positive with low titers. For WT1, positive results were detected in 39 of 97 samples and 7 (2 CML, 1 ALL, 2 lymphoma and 2 RCC) patients clearly showed positive results more than once. On the basis of these results, we performed serial analyses of WT1-specific CTL during the clinical course in 2 patients with RCC, who underwent HSCT with a reduced-intensity regimen, to examine the precise correlation between the kinetics of CTL, the occurrence of GVHD and the observed clinical response. A higher positive rate for WT1-specific CTL and a correlation with the clinical response suggest that WT1 may be a useful antigen for a wider monitoring application.

Adult↗
PubMed2006

Pleiotropic role of histone deacetylases in the regulation of human adult erythropoiesis.

Histone acetylation and deacetylation play fundamental roles in transcriptional regulation. We investigated the role of histone deacetylases (HDACs) in human adult haematopoiesis, using the structurally distinct HDAC inhibitors FK228 (depsipeptide) and Trichostatin A. When CD34+ cells were cultured with interleukin (IL)-3 or stem cell factor (SCF) + IL-3, FK228 (0.5 ng/ml) specifically enhanced the generation of immature erythroid cells with a CD36+ glycophorin A (GPA)low phenotype. In semisolid cultures, FK228 promoted the formation of erythroid colonies by CD34+ cells with IL-3 and SCF + IL-3. Furthermore, upon exposure to FK228, CD34+ cell-derived CD36+ GPA- cells were induced to form erythroid colonies with IL-3 alone. Conversely, FK228 inhibited the generation of CD36+ GPAhigh relatively mature erythroid cells from CD34+ cells in the presence of erythropoietin (EPO) and SCF + EPO. FK228 suppressed the EPO-mediated survival of CD36+ GPAlow/- and CD36+ GPAhigh cells and induced their apoptosis. Similar effects were observed for trichostatin A in the generation of erythroid cells in IL-3- and EPO-containing cultures. These data suggest that HDACs negatively regulate the IL-3-mediated growth of early erythroid precursors by suppressing their responsiveness to IL-3, while playing an important role in EPO-mediated differentiation and survival of erythroid precursors. Our data revealed that HDACs have diverse functions in human adult erythropoiesis.

Adult↗
PubMed2006

Modulation of acute graft-versus-host disease and chimerism after adoptive transfer of in vitro-expanded invariant Valpha14 natural killer T cells.

Mouse natural killer T cells with an invariant Valpha14-Jalpha18 TCR rearrangement (Valpha14i NKT cells) are able to regulate immune responses through rapid and large amounts of Th1 and Th2 cytokine production. It has been reported that in vivo administration of the Valpha14i NKT cell ligand, alpha-galactosylceramide (alpha-GalCer) significantly reduced morbidity and mortality of acute graft-versus-host disease (GVHD) in mice. In this study, we examined whether adoptive transfer of in vitro-expanded Valpha14i NKT cells using alpha-GalCer and IL-2 could modulate acute GVHD in the transplantation of spleen cells of C57BL/6 mice into (B6xDBA/2) F(1) mice. We found that the adoptive transfer of cultured spleen cells with a combination of alpha-GalCer and IL-2, which contained many Valpha14i NKT cells, modulated acute GVHD by exhibiting long-term mixed chimerism and reducing liver damage. Subsequently, the transfer of Valpha14i NKT cells purified from spleen cells cultured with alpha-GalCer and IL-2 also inhibited acute GVHD. This inhibition of acute GVHD by Valpha14i NKT cells was blocked by anti-IL-4 but not by anti-IFN-gamma monoclonal antibody. Therefore, the inhibition was dependent on IL-4 production by Valpha14i NKT cells. Our findings highlight the therapeutic potential of in vitro-expanded Valpha14i NKT cells for the prevention of acute GVHD after allogeneic hematopoietic stem cell transplantation.

Acute Disease↗
PubMed2006

Myeloablative allogeneic hematopoietic stem cell transplantation for non-Hodgkin lymphoma: a nationwide survey in Japan.

We retrospectively surveyed the data of 233 patients who underwent myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) for non-Hodgkin lymphoma (NHL). Donors were HLA-matched relatives in 154 patients (66%) or unrelated volunteers in 60 (26%). Ninety patients (39%) were in complete remission. One hundred ninety-three (83%) received a total body irradiation (TBI)-based regimen, and 40 (17%) received a non-TBI-based regimen. Acute graft-versus-host disease (GVHD) occurred in 155 (67%) of the 233 evaluable patients; grade II to IV in 90 (39%), and grade III to IV in 37 (16%). Treatment-related mortality (TRM) was observed in 98 patients (42%), and 68% of them were related to GVHD. In a multivariate analysis, chemoresistance, prior autograft, and chronic GVHD were identified as adverse prognostic factors for TRM. Relapse or progression of lymphoma was observed in 21%. The 2-year overall survival rates of the patients with indolent (n = 38), aggressive (n = 111), and lymphoblastic lymphoma (n = 84) were 57%, 42%, and 41%, respectively. In a multivariate analysis, chemoresistance, prior autograft, and prior radiotherapy were identified as adverse prognostic factors for overall survival. Although myeloablative allo-HSCT represents an effective therapeutic option for patients with NHL, more work is still needed to decrease TRM and relapse.

Acute Disease↗
PubMed2006

Coincidental outbreak of methicillin-resistant Staphylococcus aureus in a hematopoietic stem cell transplantation unit.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common nosocomial pathogens among hospital-acquired infections, and immunocompromised patients are highly susceptive to infection. The molecular typing of isolated strains is a common method for tracing an outbreak of MRSA, but experience with this approach is still limited in the hematopoietic stem cell transplantation (HSCT) ward. METHODS: We experienced 6 cases of MRSA infection/colonization in our 26-bed HSCT ward during a 4-week period. This unusual outbreak strongly suggested that the same MRSA strain was involved despite strict isolation and aseptic patient care. Clarification of the transmission pattern was critical, and we applied pulsed-field gel electrophoresis (PFGE) and amplified fragment length polymorphism (AFLP) assays for evaluation. RESULTS AND CONCLUSION: In four of the six cases, the pattern of bands examined by PFGE and AFLP analyses supported the idea that direct person-to-person transmission was very unlikely and the outbreak was coincidental. This experience highlights the clinical value of molecular typing methods for the clinical epidemiological assessment of MRSA outbreak.

Adult↗
PubMed2006

Nutritional support for patients suffering from intestinal graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Patients who exhibit gastrointestinal (GI) involvement due to graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (SCT) are often recommended to withhold oral intake (NPO) to avoid further damage to the GI mucosa. However, it is possible that continuing oral intake could be beneficial in many patients compared to total parenteral nutrition (TPN). OBJECTIVE: The primary objective of this prospective study was to evaluate whether programmed step-ladder oral dieting (enteral nutrition; EN) is feasible and beneficial for these patients. METHODS: A total of 18 patients who exhibited GI-acute GVHD (stage I to III gut GVHD) after SCT received an EN dieting program, and changes in clinical and laboratory parameters were compared to those in a control cohort of 17 patients who were placed on NPO with TPN. Patients with GVHD were included prospectively and those with intestinal bleeding/obstruction, severe pancreatitis, and cytomegalovirus enterocolitis were excluded. RESULTS: None of the patients in the EN group experienced significant adverse events, including exacerbation of GI symptoms. Although there was no statistically significant difference in the volume or frequency of diarrhea or the time to complete dietary recovery, parameters including body weight and serum levels of total protein and albumin tended to improve faster in the EN group. CONCLUSION: The EN diet is safely applicable to patients suffering from GI involvement by GVHD.

Adult↗
PubMed2006

Intensive multimodality therapy including paclitaxel and reduced-intensity allogeneic hematopoietic stem cell transplantation in the treatment of adrenal cancer with multiple metastases.

Adrenocortical carcinoma is a rare malignancy in adolescents and young adults. The prognosis of unresectable/metastatic adrenocortical carcinoma remains very poor because the rarity of the tumor has made it difficult to establish treatment guidelines, and diagnosis and the resultant treatment can be greatly delayed. We treated a 24-year-old woman who was diagnosed with adrenocortical carcinoma of the right adrenal gland which extended to the inferior vena cava. Although she underwent surgical resection of the extensive tumor as the primary treatment, the disease recurred in the lung and liver as multiple metastases shortly after surgery. She received intensive multimodality therapy, including chemotherapy with paclitaxel, ifosfamide, and cisplatin (TIP regimen), embolization of the feeding arteries, and proton irradiation for the liver mass. Finally, she underwent reduced-intensity allogeneic hematopoietic stem cell transplantation from an HLA 1-locus-mismatched sibling donor. A prolonged survival of 39 months after the onset of the disease was achieved. Although this experience is limited, we suggest that TIP chemotherapy was effective for adrenocortical carcinoma, and a graft-versus-tumor effect after reduced-intensity stem cell transplantation may have contributed to the prolonged survival.

Adrenal Gland Neoplasms↗
PubMed2006

Early detection of plasma cytomegalovirus DNA by real-time PCR after allogeneic hematopoietic stem cell transplantation.

Cytomegalovirus (CMV) infection is an important cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Therefore, preemptive ganciclovir therapy based on early detection of CMV reactivation is widely used to prevent CMV disease. Real-time polymerase chain reaction (PCR) has been widely used for monitoring CMV reactivation as well as the antigenemia assay that detects CMV structural phosphoprotein with a molecular weight of 65,000 (pp65). We developed a real-time PCR assay system for CMV based on a double-stranded DNA-specific dye, SYBR Green I, and quantified DNA, which was extracted automatically from plasma. This real-time PCR assay and the pp65 antigenemia assay were compared in parallel with 357 blood samples obtained from 64 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). Real-time PCR assay results correlated with those of the pp65 antigenemia assay (p < 0.0001). It is noteworthy that the detection of CMV DNA by PCR preceded the first positive antigenemia by 14 days. In this study, 10 of 64 patients developed CMV disease. The antigenemia assay detected CMV reactivation earlier than the development of CMV disease only in four of 10 patients. In contrast, our real-time PCR detected CMV-DNA before the development of CMV diseases in eight of 10 patients. The real-time PCR with SYBR Green I as a detection signal is simple and readily performed, and may be a useful system for early detection of CMV reactivation after allo-HSCT.

Cytomegalovirus↗
PubMed2005

Cytokine production and migration of in vitro-expanded NK1.1(-) invariant Valpha14 natural killer T (Valpha14i NKT) cells using alpha-galactosylceramide and IL-2.

Mouse natural killer T cells with invariant Valpha14 rearrangement (Valpha14i NKT cells) can rapidly produce both Th1 and Th2 cytokines and regulate various immune responses, such as autoimmunity and tumor immunity. In this study, we describe the phenotypical and functional characterization of in vitro-expanded mouse Valpha14i NKT cells from spleen using a combination of alpha-galactosylceramide (alpha-GalCer) and IL-2. The expanded Valpha14i NKT cells retained the memory/activated (CD44(+)CD69(+)CD62L(-)) and CD4(+) or CD4(-)8(-) double negative phenotypes but modulated or lost the classical NKT cell marker, NK1.1. The expanded Valpha14i NKT cells continuously released IL-4 and IFNgamma and induced NK cell IFNgamma production in vitro. Furthermore, the expanded Valpha14i NKT cells migrated into the liver and spleen after adoptive transfer into lymphopenic SCID mice, and they were able to rapidly produce IL-4 and IFNgamma after alpha-GalCer injection. Our findings suggest that the intrinsic characteristics of the cytokine secretion of Valpha14i NKT cells were equivalent to that of in vitro-expanded Valpha14i NKT cells. In vitro-expanded Valpha14i NKT cells are considered to be useful for NKT cell defect-related diseases, such as autoimmunity and cancer.

Animals↗
PubMed2005

A prospective trial to evaluate the safety and efficacy of pravastatin for the treatment of refractory chronic graft-versus-host disease.

This prospective study evaluates the safety and efficacy of pravastatin for the treatment of chronic graft-versus-host disease (GVHD). We included 18 patients with refractory chronic GVHD. Oral pravastatin was started at 10 mg/day, and the dose was increased up to 40 mg/day in 4 weeks. This maximum dose was administered over 8 weeks. There were no severe adverse events caused by pravastatin. A clinical response was observed in the skin score in two patients, mouth score in five patients, eye score in two patients, liver score in three patients, platelet count score in one patient, and weight loss in two patients. The overall response rate was 28%. Immunophenotypic analyses showed that T-helper (Th)1 cells were dominant in all but one patient before treatment and that the Th1/Th2 ratio tended to be lower in the responders than in the nonresponders. A randomized controlled trial is warranted to evaluate the efficacy of pravastatin against chronic GVHD.

Chronic Disease↗
PubMed2005

Clinical response in Japanese metastatic melanoma patients treated with peptide cocktail-pulsed dendritic cells.

BACKGROUND: Metastatic, chemotherapy-resistant melanoma is an intractable cancer with a very poor prognosis. As to immunotherapy targeting metastatic melanoma, HLA-A2+ patients were mainly enrolled in the study in Western countries. However, HLA-A24+ melanoma patients-oriented immunotherapy has not been fully investigated. In the present study, we investigated the effect of dendritic cell (DC)-based immunotherapy on metastatic melanoma patients with HLA-A2 or A24 genotype. METHODS: Nine cases of metastatic melanoma were enrolled into a phase I study of monocyte-derived dendritic cell (DC)-based immunotherapy. HLA-genotype analysis revealed 4 cases of HLA-A*0201, 1 of A*0206 and 4 of A*2402. Enriched monocytes were obtained using OptiPreptrade mark from leukapheresis products, and then incubated with GM-CSF and IL-4 in a closed serum-free system. After pulsing with a cocktail of 5 melanoma-associated synthetic peptides (gp100, tyrosinase, MAGE-2, MAGE-3 and MART-1 or MAGE-1) restricted to HLA-A2 or A24 and KLH, cells were cryopreserved until used. Finally, thawed DCs were washed and injected subcutaneously (s.c.) into the inguinal region in a dose-escalation manner. RESULTS: The mean percentage of DCs rated as lin-HLA-DR+ in melanoma patients was 46.4 +/- 15.6 %. Most of DCs expressed high level of co-stimulatory molecules and type1 phenotype (CD11c+HLA-DR+), while a moderate number of mature DCs with CD83 and CCR7 positive were contained in DC products. DC injections were well tolerated except for transient liver dysfunction (elevation of transaminases, Grade I-II). All 6 evaluable cases except for early PD showed positive immunological responses to more than 2 melanoma peptides in an ELISPOT assay. Two representative responders demonstrated strong HLA-class I protein expression in the tumor and very high scores of ELISPOT that might correlate to the regression of metastatic tumors. Clinical response through DC injections was as follows : 1CR, 1 PR, 1SD and 6 PD. All 59 DC injections in the phase I study were tolerable in terms of safety, however, the maximal tolerable dose of DCs was not determined. CONCLUSIONS: These results suggested that peptide cocktail-treated DC-based immunotherapy had the potential for utilizing as one of therapeutic tools against metastatic melanoma in Japan.

Journal Article↗
PubMed2005

Chest computed tomography of late invasive aspergillosis after allogeneic hematopoietic stem cell transplantation.

Computed tomography (CT) is a powerful diagnostic tool for invasive aspergillosis (IA) after allogeneic stem cell transplantation (allo-SCT); however, little information is available concerning CT findings of late IA after allo-SCT. To characterize CT findings of late IA, we retrospectively examined medical records and high-resolution CT findings of 27 allo-SCT recipients with late IA. Either acute or chronic GVHD was diagnosed in 24 patients. All 27 patients were given corticosteroids at IA diagnosis. High-resolution CT findings included halo (n=12), centrilobular nodules (n=12), ill-defined consolidation (n=13), ground-glass attenuation (n=8), pleural effusion (n=7), pleural-based consolidation (n=4), and cavitation (n=4). CT findings showing centrilobular nodules and either halo or cavitation were classified into bronchopneumonia type and angioinvasive type, respectively. Angioinvasive-type, bronchopneumonia-type, and combination-type IA were diagnosed in 11, 8, and 4 patients, respectively. CT findings were nonspecific in the other 4 patients. One bronchopneumonia-type case and 2 angioinvasive-type IA cases were subsequently diagnosed as combination type. Although there were no significant differences in patient characteristics between the 2 types of IA, bronchopneumonia-type IA had a poorer prognosis than angioinvasive IA ( P=.022). Halo is a useful diagnostic marker in late IA as well as early IA, and late IA frequently manifests as bronchopneumonia.

Adrenal Cortex Hormones↗
PubMed2005

Outcomes of patients with acute leukaemia who relapsed after reduced-intensity stem cell transplantation from HLA-identical or one antigen-mismatched related donors.

The characteristics of relapse following reduced-intensity stem-cell transplantation (RIST) remain to be clarified. We reviewed the medical records of 19 patients with acute leukaemia [acute myeloid leukaemia (AML), 16; acute lymphoblastic leukaemia (ALL), 3] who relapsed after RIST from related donors using purine-analogue-based regimens. Their median age was 55 years (range, 29-65 years). Median interval between RIST and relapse was 4.9 months (range, 1.8-24.9 months). Three chose not to receive interventions. The remaining 16 patients received withdrawal of immunosuppression (n = 3), chemotherapy (n = 2), donor lymphocyte infusion (n = 10) and second transplantation (n = 7), alone (n = 9) or in combination (n = 7). Four are alive with a median follow-up of 27.6 months (range, 16.0-28.9 months); three in remission and one in relapse. The 2-year overall survival after relapse was 28.9%. Causes of death in 15 patients included progressive disease (n = 7), graft-versus-host disease (n = 5) and infections (n = 3). Cumulative incidences of relapse-related and non-relapse-related deaths at 2 years after relapse were 37% and 32% respectively. Two prognostic factors were identified on univariate analysis: age [P = 0.017; hazard ratio (HR), 1.16; 95% confidence interval (CI), 1.03-1.32], and ALL as underlying disease (P = 0.011; HR, 10.4; 95% CI, 1.73-62.4). Some AML patients who relapse after RIST achieve durable remission with allogeneic immunotherapy-based interventions; however they carry a significant risk of non-relapse mortality.

Acute Disease↗
PubMed2005

Impact of human leucocyte antigen mismatch on graft-versus-host disease and graft failure after reduced intensity conditioning allogeneic haematopoietic stem cell transplantation from related donors.

The impact of human leucocyte antigen (HLA) incompatibility between donor and recipient on graft-versus-host disease (GVHD) and graft failure after reduced-intensity conditioning stem cell transplantation (RICT) remains to be elucidated. We retrospectively analysed outcome in 341 patients who underwent RICT from related donors for haematological malignancies. The overall cumulative incidence of grade II-IV acute GVHD (aGVHD) was 40% for all subjects; 39% in recipients with HLA-matched donors, 44% in those with one-locus-mismatched donors, and 50% in those with two- to three-loci-mismatched donors. In a Cox regression model adjusted for potential confounders, the tendency for grade II-IV aGVHD (P=0.01), chronic GVHD (cGVHD) (P=0.05) and graft failure (P=0.033) increased with HLA disparity. Use of peripheral blood grafts instead of marrow was a risk factor for cGVHD. Use of antithymocyte globulin was associated with reduced aGVHD and cGVHD. Overall survival (OS) in recipients of two- to three-loci-mismatched RICT at 2 years (18%) was significantly worse than that in patients who received one-locus-mismatched RICT (51%) and HLA-matched RICT (48%) (P<0.0001). A two- to three-loci mismatch was identified as an independent risk factor for OS (P<0.001), but there was no significant difference in OS between HLA-matched and one-locus-mismatched RICT. HLA incompatibility between the donor and recipient is an important risk factor for graft failure, aGVHD, cGVHD and OS after RICT. RICT from a one-locus-mismatched donor may represent an effective alternative approach in patients with high-risk malignancies who lack HLA-matched related donors.

Acute Disease↗
PubMed2005

Evaluation of cytomegalovirus-specific T-cell reconstitution in patients after various allogeneic haematopoietic stem cell transplantation using interferon-gamma-enzyme-linked immunospot and human leucocyte antigen tetramer assays with an immunodominant T-cell epitope.

Cytomegalovirus (CMV) infection is a major complication for patients who received allogeneic haematopoietic stem cell transplantation (HSCT). Accurate monitoring of CMV-specific T-cell reconstitution is required for appropriate decision on treatment, such as anti-viral drugs, which have adverse effects. Although human leucocyte antigen (HLA) tetramer and interferon-gamma-enzyme-linked immunospot (IFN-gamma-ELISPOT) assays have been used to measure CMV-specific T cells, detailed comparison of these assays and kinetics of anti-CMV T-cell reconstitution between reduced-intensity transplantation (RIST) and conventional HSCT has not yet been performed. In this study, we performed prospective comparative monitoring of CMV-specific T cells using HLA tetramer and IFN-gamma-ELISPOT assays with a single immunodominant CMV(495) peptide in 28 HLA-A*0201 and 9 HLA-A*0206 patients after various allogeneic HSCTs. The IFN-gamma-ELISPOT assay was more sensitive for evaluation of functional T cells than the HLA tetramer assay, and CMV-specific T cells were reconstituted earlier in patients who received RIST without anti-thymocyte globulin (ATG) than those receiving RIST with ATG or conventional HSCT. The threshold level for protection from CMV reactivation was estimated as over 1 x 10(6) cells/l peripheral blood with the IFN-gamma-ELISPOT assay. These results demonstrate that the IFN-gamma-ELISPOT assay with CMV(495) provides more accurate evaluation on CMV immunity in HLA-A*0201 and -A*0206 patients, and may be useful for determining timing of various treatments.

Adolescent↗
PubMed2005

Phenotypical and functional alterations during the expansion phase of invariant Valpha14 natural killer T (Valpha14i NKT) cells in mice primed with alpha-galactosylceramide.

Invariant Valpha14 natural killer T (Valpha14i NKT) cells are a unique immunoregulatory T-cell population that is restricted by CD1d. The glycolipid alpha-galactosylceramide (alpha-GalCer) is presented by CD1d and causes robust Valpha14i NKT-cell activation. Three days after injection of alpha-GalCer, Valpha14i NKT cells vigorously increase in number and then gradually decrease to normal levels. In the present study, we found that the re-administration of alpha-GalCer into mice primed 3 days earlier causes a marked increase in serum interleukin-4 and interferon-gamma. Intracellular staining revealed that the only expanded Valpha14i NKT cells are responsible for the enhanced cytokine production. The enhanced cytokine production was correlated with an increased number of Valpha14i NKT cells after priming. Additionally, primed Valpha14i NKT cells produced larger amounts of cytokine as compared with naive Valpha14i NKT cells when cultured with alpha-GalCer-pulsed dendritic cells. Thus, we considered that a subset of expanded Valpha14i NKT cells acquired a strong ability to produce cytokines. In contrast to mice primed 3 days earlier, cytokine production is markedly diminished in mice primed 7 days earlier. The expanded Valpha14i NKT cells altered the surface phenotype (NK1.1- CD69-) and contained intracellular interferon-gamma. Additionally, we found that primed Valpha14i NKT cells did not disappear or down-regulate surface TCR expression when re-injected with alpha-GalCer as compared with naive Valpha14i NKT cells. These results demonstrate that the function and surface phenotype of Valpha14i NKT cells is dramatically altered after alpha-GalCer priming.

Animals↗
PubMed2005

Prospective trial of high-dose chemotherapy followed by infusions of peripheral blood stem cells and dose-escalated donor lymphocytes for relapsed leukemia after allogeneic stem cell transplantation.

To determine whether induction of graft-versus-host disease (GVHD) improves the outcome of acute relapsed leukemia after stem cell transplantation (SCT), we used high-dose cytarabine (ara-C) followed by infusions of donor-derived buffy coats containing peripheral blood stem cells to treat 12 patients with relapsed leukemia. Donor lymphocyte infusion (DLI) was repeated at least twice over a 5-week interval for patients in whom grade II to IV acute GVHD did not develop after the first DLI. Grade II to IV acute GVHD developed in 4 (33%) of the patients. Chronic GVHD developed in 3 patients, 2 of whom had not experienced acute GVHD. Four (67%) of the 6 patients who developed grade II to IV acute and/or chronic GVHD after DLI responded, but none of the other 6 patients responded. Four (33%) of the patients (2 with acute myelogenous leukemia [AML] and 2 with acute lymphoblastic leukemia [ALL]) achieved complete remission lasting longer than 4 months after the first DLI, but 3 of them had relapses in bone sites. Of these 4 patients, 1 patient with AML and 2 with ALL were alive 8 to 27 months after DLI. These findings indicate that high-dose ara-C combined with megadose DLI may produce durable remission of acute leukemia that has relapsed after SCT when GVHD is induced. The low induction rate of GVHD and extramedullary relapse after remission is achieved with DLI are problems yet to be solved.

Adult↗