ABSTRACT
Background@#Allogeneic hematopoietic stem cell transplantation (alloSCT) is a potentially curative treatment option for acute leukemia. We aimed to identify the comorbidity factors affecting survival outcomes after alloSCT and develop a new comorbidity index tool for predicting overall survival (OS). @*Methods@#A Korean nationwide cohort of 3,809 adults with acute leukemia treated with alloSCT between January 2002 and December 2018 was analyzed as the development cohort.A retrospective cohort comprising 313 consecutive adults with acute leukemia who underwent alloSCT between January 2019 and April 2020 was analyzed as the validation cohort. @*Results@#In the development cohort, advanced age, male sex, and comorbidities such as previous non-hematologic malignancy, hypertension, and coronary or cerebral vascular disease were significantly related to poor OS. Subsequently, a new comorbidity scoring system was developed, and risk groups were created, which included the low-risk (score ≤0.17), intermediate-risk (0.17＜ score ≤0.4), high-risk (0.4＜ score ≤0.55), and very high-risk (score ＞0.55) groups. The 1-year OS rates were discriminatively estimated at 73.5%, 66.2%, 61.9%, and 50.9% in the low-risk, intermediate-risk, high-risk, and very high-risk groups in the development cohort, respectively (P ＜0.001). The developed scoring system yielded discriminatively different 1-year OS rates and 1-year incidence of non-relapse mortality according to the risk group (P =0.085 and P =0.018, respectively).Furthermore, the developed model showed an acceptable performance for predicting 1-year non-relapse mortality with an area under the curve of 0.715. @*Conclusion@#The newly developed predictive scoring system could be a simple and reliable tool helping clinicians to assess risk of alloSCT in adults with acute leukemia.
ABSTRACT
Background/Aims@#Idiopathic multicentric Castleman disease (iMCD) comprises approximately 30% of all cases of Castleman disease. It is characterized by constitutional symptoms, enlarged lymph nodes at multiple anatomical sites, and laboratory test abnormalities, which are primarily related to the overproduction of interleukin 6 (IL-6). Siltuximab is a human-mouse chimeric immunoglobulin G1κ monoclonal antibody against human IL-6. In view of the limited treatment options for iMCD, this study aimed to evaluate the efficacy and safety of siltuximab in the management of this condition. @*Methods@#In this real-world retrospective study, we administered siltuximab to 15 patients with iMCD who previously received conventional chemotherapy and/or steroid pulse therapy. The median time to a durable symptomatic response was 22 days (range, 17 to 56). The serum hemoglobin and albumin levels and erythrocyte sedimentation rates significantly normalized after the first 3 months of siltuximab treatment. Lymph node involution, assessed using imaging, was relatively gradual, demonstrating a complete or partial response at 6 months. @*Results@#On an average, the improvements in clinical, laboratory, and radiologic parameters of iMCD in responders were observed after one, three, and eight cycles of siltuximab treatment, respectively. Siltuximab demonstrated a favorable safety profile, and prolonged treatment was well-tolerated. @*Conclusions@#Despite the small sample size of the present study, the results are encouraging and demonstrate the potential of siltuximab as the first-line treatment of iMCD. Further large multicenter studies are needed to evaluate the clinical outcomes and adverse events associated with siltuximab.
ABSTRACT
Background@#Allogeneic hematopoietic stem cell transplantation (alloSCT) is a potentially curative treatment option for acute leukemia. We aimed to identify the comorbidity factors affecting survival outcomes after alloSCT and develop a new comorbidity index tool for predicting overall survival (OS). @*Methods@#A Korean nationwide cohort of 3,809 adults with acute leukemia treated with alloSCT between January 2002 and December 2018 was analyzed as the development cohort.A retrospective cohort comprising 313 consecutive adults with acute leukemia who underwent alloSCT between January 2019 and April 2020 was analyzed as the validation cohort. @*Results@#In the development cohort, advanced age, male sex, and comorbidities such as previous non-hematologic malignancy, hypertension, and coronary or cerebral vascular disease were significantly related to poor OS. Subsequently, a new comorbidity scoring system was developed, and risk groups were created, which included the low-risk (score ≤0.17), intermediate-risk (0.17＜ score ≤0.4), high-risk (0.4＜ score ≤0.55), and very high-risk (score ＞0.55) groups. The 1-year OS rates were discriminatively estimated at 73.5%, 66.2%, 61.9%, and 50.9% in the low-risk, intermediate-risk, high-risk, and very high-risk groups in the development cohort, respectively (P ＜0.001). The developed scoring system yielded discriminatively different 1-year OS rates and 1-year incidence of non-relapse mortality according to the risk group (P =0.085 and P =0.018, respectively).Furthermore, the developed model showed an acceptable performance for predicting 1-year non-relapse mortality with an area under the curve of 0.715. @*Conclusion@#The newly developed predictive scoring system could be a simple and reliable tool helping clinicians to assess risk of alloSCT in adults with acute leukemia.
ABSTRACT
Hepatic sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a rare but severe complication of hematopoietic cell transplantation (HCT) showing high mortality. Multiple risk factors for SOS/VOD were identified, but it is often confused with other hepatic complications due to nonspecific clinical features. Therefore, diagnostic and severity criteria have been revised several times. The European Society of Blood and Marrow Transplantation suggested a new guideline that excludes the standard duration of development within 21 days, emphasizes late-onset SOS/VOD, and suggests the importance of Doppler ultrasonography. The severity criteria were further subdivided for guidance to begin active treatment using defibrotide which was approved in Korea since 2016. In a phase 3 trial, defibrotide had superior 100-day survival, compared to best available treatments (38.2% vs. 25.0%). Although several studies of SOS/VOD in Korean patients have been performed after the implementation of HCT, most involved small number of pediatric patients. Recently, the Korean Society of Blood and Marrow Transplantation investigated the incidence of SOS/VOD in the Korean population, and several influential studies of adult patients were published. Here, we summarize recent issues regarding the mechanism, diagnosis, severity criteria, prevention, and treatments of SOS/VOD in Korean patients, as well as recent analyses of nationwide incidence.
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Standard post-remission therapy for adult patients with high-risk acute lymphoblastic leukemia (ALL) is allogeneic hematopoietic cell transplantation (allo-HCT). However, 20–30% of patients treated with allo-HCT subsequently relapse, and their long-term survival outcomes are very poor even after the next allo-HCT. The poor survival outcomes reported by previous studies have mainly been due to low complete remission (CR) rates and high mortality from conventional salvage chemo-regimens, such as mitoxantrone plus etoposide plus cytarabine (MEC) or fludarabine plus cytarabine plus idarubicin (FLA-Ida). However, several novel agents with proven high remission rates and a good measurable residual disease response can now be administered. The representative novel agents recently introduced are blinatumomab (anti-CD19 bispecific T-cell engager) and inotuzumab ozogamicin (anti-CD22 antibody-calicheamicin conjugate). In South Korea, blinatumomab has been used since October 2016 and inotuzumab ozogamicin has been in use since October 2019 under coverage by the national insurance system. Studies on blinatumomab in Korea showed that this drug is effective when used as an early salvage line, even in patients who relapse after an initial allo-HCT. However, a previous study revealed that relapsed patients with a short CR duration of < 12 months post-HCT show a poor response to blinatumomab compared to patients with a longer CR duration. Also, some early relapsed cases with active acute graft-versus-host disease (GVHD) show aggravated GVHD with the use of blinatumomab. No real-world data are available in Korea for inotuzumab, but previous trials have reported a good CR and proceeding rates to allo-HCT comparable to blinatumomab. We have experienced hepatotoxicity including venoocclusive disease in post-HCT relapsed patients treated with inotuzumab.
ABSTRACT
BACKGROUND AND OBJECTIVES: Cells of innate immunity normally recover in the first weeks to months after allogenenic hematopoietic stem cell transplantation (allo-HSCT). Their relevance in terms of graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect is largely unknown. The predictive role of early recovery in the immune cells on acute GVHD and GVL effect after allo-HSCT was investigated in patients with acute leukemia who achieved the first complete remission. METHODS: Peripheral blood samples were taken at the median of 14 days (range, 12~29 days) after allo-HSCT. A cohort including 119 samples and characteristics of patients were analyzed. Immune cell populations were identified by flow cytometry. RESULTS: The median age was 49.0 years (range, 21~69) at transplantation. Univariate analysis showed that age less than 40 years old, lower frequencies of CD8+ T cells, invariant natural killer T (iNKT) cells, monocytic myeloid derived suppressor cells (M-MDSCs) and higher frequency of immature MDSCs were associated with occurrence of grade III–IV acute GVHD. Multivariate analyses showed that iNKT cells (hazard ratio (HR), 0.453, 95% CI, 0.091~0.844, p=0.024) and M-MDSCs (HR, 0.271, 95% CI, 0.078~0.937, p=0.039) were independent factors. Combination of higher frequencies of both cell subsets was associated with lower incidence of grade III–IV acute GVHD, whereas patients with lower frequency of iNKT cells and higher frequency of M-MDSCs showed significant higher probability of relapse. CONCLUSIONS: iNKT cells and M-MDSCs could be relevant cell biomarkers for predicting acute GVHD and/or relapse in acute leukemia patients treated with allo-HSCT.
Subject(s)
Humans , Biomarkers , Cohort Studies , Flow Cytometry , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cells , Immunity, Innate , Incidence , Leukemia , Multivariate Analysis , Natural Killer T-Cells , Recurrence , T-LymphocytesABSTRACT
BACKGROUND: The aim of this study was to evaluate the effects of darbepoetin alfa (DA) on hemoglobin (Hb) concentration and the need for transfusions in multiple myeloma (MM) patients receiving chemotherapy with novel agents. METHODS: Of 251 patients with MM who received DA therapy for at least 4 weeks, 142 who did not receive RBC transfusion during 4 weeks after DA initiation and started DA therapy at baseline Hb <10.0 g/dL were analyzed. RESULTS: After 4 weeks of DA therapy, 80 (60.6%) of 132 patients with evaluable data had Hb that increased ≥1.0 g/dL from baseline, while 50 (37.9%) had Hb that increased ≥2.0 g/dL from baseline. Pretreatment Hb level did not correlate with the proportion of patients with increased Hb. The median duration of DA therapy was 9.0 weeks. At the end of DA therapy, of 135 patients with evaluable data, 86 (60.6%) had Hb that increased ≥1.0 g/dL from baseline, while 67 (47.2%) had Hb that increased ≥2.0 g/dL from baseline. Stage III disease according to the International Staging System and absence of myeloma bone disease at diagnosis were independent predictors of higher Hb response during early DA therapy. CONCLUSION: We demonstrated the efficacy of DA therapy in a homogeneous group of MM patients receiving chemotherapy. DA therapy significantly increased Hb concentration, regardless of baseline Hb level.
Subject(s)
Humans , Anemia , Bone Diseases , Darbepoetin alfa , Diagnosis , Drug Therapy , Erythropoietin , Multiple MyelomaABSTRACT
This retrospective study aimed to compare the clinical features of paramedullary lesions (PLs) and extramedullary lesions (ELs) of plasmacytomas at diagnosis, using positron emission tomography integrated with computed tomography, using glucose labeled with the positron-emitting radionuclide ¹⁸F (¹⁸F-FDG-PET/CT) in newly diagnosed multiple myeloma (NDMM), and to address their prognostic impact. Sixty-four patients with NDMM presenting ELs (n=22) and/or PLs (n=42) were included. Patients with ELs at initial presentation had unfavorable laboratory parameters of calcium and lactate dehydrogenase, a higher percentage of bone marrow plasma cells, and showed a trend toward advanced international staging system (ISS), compared to patients with PLs. Using X-ray imaging, high bone disease (HBD) was observed in 50% and 71% of patients with ELs and PLs, respectively. After a median follow-up of 29.2 months (range, 3.4–76.5 months) in survivors, patients with ELs had a significantly lower overall survival (OS) (p=0.033) than patients with PLs did, whereas the progression-free survival (PFS) did not differ significantly (p=0.818). However, the PFS after 1(st) progression was significantly worse in patients with ELs than in those with PLs (p=0.017). In the multivariate analyses, the negative impact of initial ELs on OS (p=0.033) was sustained. Our results demonstrated the different clinical features and outcomes of ELs and PLs in NDMM. Patients with initial ELs showed a shorter PFS after 1(st) progression, which translated into poor OS, providing insight into the different biological effect of ELs.
Subject(s)
Humans , Bone Diseases , Bone Marrow , Calcium , Diagnosis , Disease-Free Survival , Follow-Up Studies , Glucose , L-Lactate Dehydrogenase , Multiple Myeloma , Multivariate Analysis , Plasma Cells , Plasmacytoma , Positron-Emission Tomography , Retrospective Studies , SurvivorsABSTRACT
BACKGROUND: Standard remission induction chemotherapy consisting of anthracycline plus cytarabine (3+7) is administered for adult acute myeloid leukemia (AML). However, the effects of intensified regimen on complete remission (CR), relapse and overall survival (OS) remain unknown. METHODS: We analyzed 1195 patients treated with idarubicin plus cytarabine/BHAC (3+7) from 2002 to 2013. Among them, 731 received early intensification with 3-day cytarabine/BHAC (3+10, N=363) or 2-day idarubicin plus cytarabine/BHAC 3 days (5+10, N=368). The 3+10 and 5+10 strategies were applied to patients with bone marrow blast counts of 5–20% and >20% on day 7 of 3+7, respectively. RESULTS: Early intensification correlated with a younger age (median: 40 vs. 45 yr) and higher t(8;21) frequency (20.4% vs. 7.1%), compared to 3+7. After early intensification, the early death rates were higher among the elderly (3+10 [15.7%], 5+10 [21.7%] vs. 3+7 [6.3%], P=0.038), while the post-induction CR rate was higher in young patients (3+10 [79.8%], 5+10 [75.1%] vs. 3+7 [65.1%], P<0.001). Early relapse rate was also decreased (3+10 [11.8%], 5+10 [11.7%] vs. 3+7 [22.0%], P<0.001). In multivariate analysis, early intensification correlated with an inferior 5-year OS among elderly patients (19.2% vs. 22.8%; hazard ratio [HR]=1.84, 95% confidence interval [CI]; 1.11–3.06, P=0.018) and lower overall relapse rate among young patients (33.0% vs. 41.4%, P=0.023; HR=0.71, 95% CI; 0.55–0.93, P=0.012). CONCLUSION: Early intensification correlated with higher CR and lower relapse rates, but not OS in young AML patients. In elderly patients, early intensification correlated with a higher early death rate and poorer OS.
Subject(s)
Adult , Aged , Humans , Bone Marrow , Cytarabine , Drug Therapy , Idarubicin , Induction Chemotherapy , Leukemia, Myeloid, Acute , Mortality , Multivariate Analysis , Recurrence , Remission InductionABSTRACT
BACKGROUND/AIMS: Recently, large cohort studies regarding associations between autoimmune disease and lymphomas have been reported in a few Western countries. However, Asian data concerning autoimmune-related lymphomas are limited. Therefore, we evaluated the clinical characteristics and prognostic factors of patients with autoimmune disease-related non-Hodgkin lymphoma (NHL) in a single center in Korea. METHODS: We analyzed the data from 11 patients with autoimmune-related NHL. Patients were categorized into two groups, those with rheumatoid arthritis (RA) and those with non-RA-related NHL. Then patients were re-categorized into a group with methotrexate (MTX) usage and a MTX non-usage group. Histological subtype, MTX duration, autoimmune disease duration, treatment modalities, and other data were collected and analyzed. RESULTS: Our study revealed that older RA patients have a greater likelihood of occurrence of NHL (p = 0.042). We confirmed that MTX duration and cumulative dose of MTX have no significant correlation with autoimmune disease and NHL (p = 0.073). In the management of autoimmune disease-related NHL, all patients were directly treated with systemic chemotherapy instead of employing a wait and watch approach. Overall survival (OS) and progression-free survival (PFS) in all autoimmune disease-related NHL were 100% and 87.5%, with no treatment-related mortality during the 2-year follow-up period of our study. CONCLUSIONS: Our study suggests that patients with RA-NHL are characterized by older age at onset compared to those with non-RA-NHL. Also considering of OS and PFS, intensive treatment strategy instead of delayed watchful managements may be required for autoimmune disease-related NHL including of old age group.
Subject(s)
Humans , Age of Onset , Arthritis, Rheumatoid , Asian People , Autoimmune Diseases , Clinical Study , Cohort Studies , Disease-Free Survival , Drug Therapy , Follow-Up Studies , Korea , Lymphoma , Lymphoma, Non-Hodgkin , Lymphoproliferative Disorders , Methotrexate , Mortality , Retrospective StudiesABSTRACT
PURPOSE: The development of bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (HSCT) deteriorates patients' quality of life. This study aimed to analyze the prevalence, clinical features, risk factors and prognostic factors of BOS. MATERIALS AND METHODS: This retrospective study included patients who underwent allogeneic HSCT from January 2002 to December 2008 and survived for > or =100 days after transplantation. RESULTS: Of 860 patients who survived for > or =100 days, 36 (4.2%) met the diagnostic criteria. The duration of BOS development after transplantation was 466.00 (284.00-642.75) [median (interquartile range)] days. The risk factor for the development of BOS was peripheral blood as the stem cell source with a hazard ratio (HR) of 2.550 [95% confidence interval (CI): 1.274-5.104, p=0.008]. In multivariate analysis, pretransplant FEV1/FVC (HR: 0.956, 95% CI: 0.921-0.993, p=0.020) and time from HSCT to diagnosis of BOS (HR: 0.997, 95% CI: 0.994-0.999, p=0.009) were independent prognostic factors associated with mortality. CONCLUSION: Peripheral blood as a stem cell source is a risk factor for the development of BOS. A decreased pretransplant FEV1/FVC and shorter duration of time from transplantation to diagnosis of BOS are poor prognostic factors for BOS.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Bronchiolitis Obliterans/epidemiology , Disease Progression , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Multivariate Analysis , Prevalence , Proportional Hazards Models , Quality of Life , Respiratory Function Tests , Retrospective Studies , Risk Factors , Survival Analysis , Transplantation, HomologousABSTRACT
BACKGROUND/AIMS: Several studies have demonstrated the effect of autologous hematopoietic stem cell transplantation (auto-HSCT) as a salvage treatment for patients with relapsed diffuse large B-cell lymphoma (DLBCL). However, the role of auto-HSCT as a frontline treatment has not been fully investigated in the rituximab era. We validated the age-adjusted International Prognostic Index (aaIPI) score for high-risk DLBCL patients and identified a possible role for frontline auto-HSCT. METHODS: We recommended frontline auto-HSCT for high-risk DLBCL patients who satisfied the criteria of both a higher Ann-Arbor stage (III to IV) and an elevated lactate dehydrogenase (LDH) level at diagnosis with an aaIPI score > or = 2. From 2006 to 2011, among the 150 DLBCL patients aged or = 2 showed inferior overall survival (OS; p = 0.040) and progression-free survival (PFS; p = 0.007) compared to the aaIPI score 0 to 1. Between the two treatment arms among the high-risk DLBCL patients, the clinical parameters were not different. The high-risk group treated with frontline auto-HSCT showed similar OS (p = 0.392) and PFS (p = 0.670) to those in the low-risk group. Thus, frontline auto-HSCT showed superior PFS (p = 0.004), but only a trend towards favorable OS (p = 0.091) compared to R-CHOP alone. CONCLUSIONS: We identified the possible role of frontline auto-HSCT for high-risk DLBCL with a higher stage (III to IV) and elevated LDH level.
Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Age Factors , Antibodies, Monoclonal, Murine-Derived/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/blood , Chemotherapy, Adjuvant , Cyclophosphamide/therapeutic use , Disease Progression , Disease-Free Survival , Doxorubicin/therapeutic use , Kaplan-Meier Estimate , L-Lactate Dehydrogenase/blood , Lymphoma, Large B-Cell, Diffuse/blood , Neoadjuvant Therapy , Neoplasm Staging , Predictive Value of Tests , Prednisone/therapeutic use , Proportional Hazards Models , Reproducibility of Results , Risk Assessment , Risk Factors , Stem Cell Transplantation , Time Factors , Transplantation, Autologous , Treatment Outcome , Up-Regulation , Vincristine/therapeutic useABSTRACT
BACKGROUND: The expression of the SOCS genes in cytomegalovirus (CMV) viremia after hematopoietic stem cell transplantation (HSCT) remains largely unexplored. METHODS: Using quantitative RT-PCR of mononuclear cells, we conducted pairwise comparison of SOCS1 and SOCS3 expression levels among a healthy donor group (N=55), a pre-HSCT group (N=17), and the recipient subgroup (N=107), which were divided according to the occurrence of CMV viremia and acute graft-versus-host disease (aGVHD). RESULTS: Compared to that in the healthy donor group, SOCS1 expression was higher in the CMV+ subgroup, especially in the CMV+GVHD- group, but decreased in the other subgroups. When compared to the expression in the pre-HSCT group, SOCS1 expression was significantly higher in the CMV+ subgroup, especially in the CMV+GVHD+ subgroup. Meanwhile, compared to that in the healthy donor group, SOCS3 expression was significantly lower in all other groups. The CMV-GVHD- subgroup showed significantly lower SOCS3 expression compared to the CMV+ subgroup, the CMV+GVHD+ subgroup, and the CMV+GVHD- subgroup. CONCLUSION: We report differential expression of SOCS genes according to CMV viremia with acute GVHD occurrence after HSCT, suggesting that regulation of SOCS expression is associated with CMV viremia.
Subject(s)
Humans , Cytomegalovirus , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Tissue Donors , ViremiaABSTRACT
Acute colonic pseudo-obstruction (ACPO), also known as Ogilvie's syndrome, is a rare clinical syndrome of massive large bowel dilatation without mechanical obstruction, which may cause significant morbidity and mortality. Treatment focuses on decompressing a severely dilated colon. The proposed theory that this severe ileus results from an imbalance in the autonomous regulation of colonic movement supports the rationale for using neostigmine, a reversible acetylcholinesterase inhibitor, in patients who failed conservative care. Although gastrointestinal complications are frequent following allogeneic stem cell transplantation (SCT), the incidence of ACPO in a transplant setting is unknown and, if not vigilant, this adynamic ileus can be underestimated. We describe the case of a patient with myelodysplastic syndrome undergoing non-myeloablative allogeneic SCT from a partially human leukocyte antigen-mismatched sibling donor, and whose clinical course was complicated by ACPO in the early post-engraftment period. The ileus was not associated with gut graft-versus-host disease or infectious colitis. After 3 days of conservative care, intravenous neostigmine (2 mg/day) was administered for 3 consecutive days. Symptoms and radiologic findings began to improve 72 hours after the initial injection of neostigmine, and complete response without any associated complications was achieved within a week. Thus, neostigmine can be a safe medical therapy with successful outcome for patients who develop ACPO following allogeneic SCT.
Subject(s)
Humans , Acetylcholinesterase , Colitis , Colon , Colonic Pseudo-Obstruction , Dilatation , Graft vs Host Disease , Ileus , Incidence , Leukocytes , Myelodysplastic Syndromes , Neostigmine , Siblings , Stem Cell Transplantation , Stem Cells , Tissue Donors , TransplantsABSTRACT
BACKGROUND: Suppressor of cytokine signaling genes (SOCS) are regarded as pivotal negative feedback regulators of cytokine signals, including the interferon-gamma (IFN-gamma), granulocyte-colony stimulating factor, and interleukin families, released by T cells. A detailed understanding of the involvement of SOCS genes in graft-versus-host disease (GVHD) is critical to effectively manage GVHD, yet their expression patterns among recipients remain largely unexplored. METHODS: Expression levels of SOCS1 and SOCS3 were determined by real-time quantitative reverse transcription PCR (qRT-PCR) in patients with acute GVHD (aGVHD) and chronic GVHD (cGVHD), in a severity-dependent manner, after allogeneic hematopoietic stem cell transplantation (HSCT). A total of 71 recipients with AML (N=40), ALL (N=12), myelodysplastic syndromes (MDS; N=10), chronic myelogenous leukemia (CML; N=2), severe aplastic anemia (SAA; N=5), or others (N=2), who received allogeneic HSCT from human leukocyte antigen-identical siblings or unrelated donors between 2009 and 2011, were included in the present study. RESULTS: Overall, the expression levels of SOCS1 decreased in recipients with grade II to IV aGVHD and cGVHD when compared to normal donors and non-GVHD recipients. Interestingly, the expressions of SOCS1 decreased significantly more in cGVHD than in aGVHD recipients (P=0.0091). In contrast, SOCS3 expressions were similarly reduced in all the recipients. CONCLUSION: This is the first study to show that SOCS1 and SOCS3 are differentially expressed in recipients following allogeneic HSCT, suggesting a prognostic correlation between SOCS genes and the development of GVHD. This result provides a new platform to study GVHD immunobiology and potential diagnostic and therapeutic targets for GVHD.
Subject(s)
Humans , Anemia, Aplastic , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cells , Interferon-gamma , Interleukins , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Leukocytes , Myelodysplastic Syndromes , Polymerase Chain Reaction , Real-Time Polymerase Chain Reaction , Reverse Transcription , Siblings , Suppressor of Cytokine Signaling Proteins , T-Lymphocytes , Tissue Donors , Transplantation, Homologous , Unrelated DonorsABSTRACT
BACKGROUND: Suppressor of cytokine signaling genes (SOCS) are regarded as pivotal negative feedback regulators of cytokine signals, including the interferon-gamma (IFN-gamma), granulocyte-colony stimulating factor, and interleukin families, released by T cells. A detailed understanding of the involvement of SOCS genes in graft-versus-host disease (GVHD) is critical to effectively manage GVHD, yet their expression patterns among recipients remain largely unexplored. METHODS: Expression levels of SOCS1 and SOCS3 were determined by real-time quantitative reverse transcription PCR (qRT-PCR) in patients with acute GVHD (aGVHD) and chronic GVHD (cGVHD), in a severity-dependent manner, after allogeneic hematopoietic stem cell transplantation (HSCT). A total of 71 recipients with AML (N=40), ALL (N=12), myelodysplastic syndromes (MDS; N=10), chronic myelogenous leukemia (CML; N=2), severe aplastic anemia (SAA; N=5), or others (N=2), who received allogeneic HSCT from human leukocyte antigen-identical siblings or unrelated donors between 2009 and 2011, were included in the present study. RESULTS: Overall, the expression levels of SOCS1 decreased in recipients with grade II to IV aGVHD and cGVHD when compared to normal donors and non-GVHD recipients. Interestingly, the expressions of SOCS1 decreased significantly more in cGVHD than in aGVHD recipients (P=0.0091). In contrast, SOCS3 expressions were similarly reduced in all the recipients. CONCLUSION: This is the first study to show that SOCS1 and SOCS3 are differentially expressed in recipients following allogeneic HSCT, suggesting a prognostic correlation between SOCS genes and the development of GVHD. This result provides a new platform to study GVHD immunobiology and potential diagnostic and therapeutic targets for GVHD.
Subject(s)
Humans , Anemia, Aplastic , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cells , Interferon-gamma , Interleukins , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Leukocytes , Myelodysplastic Syndromes , Polymerase Chain Reaction , Real-Time Polymerase Chain Reaction , Reverse Transcription , Siblings , Suppressor of Cytokine Signaling Proteins , T-Lymphocytes , Tissue Donors , Transplantation, Homologous , Unrelated DonorsABSTRACT
Tacrolimus is a widely used immunosuppressive agent for the prophylaxis of graft-versus-host disease in allogeneic hematopoietic stem cell transplantation (HSCT). Since tacrolimus is primarily metabolized by the liver, hepatic dysfunction may affect its metabolism. Hepatic veno-occlusive disease (VOD) is an early complication of HSCT that results in hepatic dysfunction, suggesting that VOD may affect tacrolimus metabolism. We report a case of hepatic VOD accompanied by a sustained high blood trough level of tacrolimus despite its discontinuation. The findings of this case suggest that the elimination of tacrolimus can be markedly delayed in patients with hepatic VOD, and that the clinician should carefully modulate the drug dosage for these patients.
Subject(s)
Humans , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cells , Hepatic Veno-Occlusive Disease , Liver , TacrolimusABSTRACT
Tacrolimus is a widely used immunosuppressive agent for the prophylaxis of graft-versus-host disease in allogeneic hematopoietic stem cell transplantation (HSCT). Since tacrolimus is primarily metabolized by the liver, hepatic dysfunction may affect its metabolism. Hepatic veno-occlusive disease (VOD) is an early complication of HSCT that results in hepatic dysfunction, suggesting that VOD may affect tacrolimus metabolism. We report a case of hepatic VOD accompanied by a sustained high blood trough level of tacrolimus despite its discontinuation. The findings of this case suggest that the elimination of tacrolimus can be markedly delayed in patients with hepatic VOD, and that the clinician should carefully modulate the drug dosage for these patients.
Subject(s)
Humans , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cells , Hepatic Veno-Occlusive Disease , Liver , TacrolimusABSTRACT
Graft-versus-host disease (GVHD) is a common complication of allogeneic stem cell transplantation (allo-SCT). However, a similar syndrome has been reported in autologous stem cell transplantation (ASCT) as well. The target organs of GVHD in ASCT are the skin, liver and gastrointestinal (GI) tract, which are consistent with those in allo-SCT. Histologic findings from the skin and the mucosa of the GI tract also show similar features. Here we describe a case of autologous GVHD involving the skin of a patient who underwent ASCT for multiple myeloma. In this patient, the response to a total prednisone dose of 0.5 mg/kg/day was unsatisfactory, and the patient required more intensive and prolonged immunosuppressive therapy with slow tapering.
Subject(s)
Humans , Gastrointestinal Tract , Graft vs Host Disease , Liver , Mucous Membrane , Multiple Myeloma , Prednisone , Skin , Stem Cell Transplantation , Stem CellsABSTRACT
The Ph-chromosome is the hallmark of chronic myelogenous leukemia (CML), but it has also been reported infrequently for de novo AML. This cytogenetic variant of AML is characterized by a poor prognosis associated with extraordinary drug resistance. Experience with the use of imatinib mesylate for Ph-chromosome-positive de novo AML is limited because of the rarity of the disorder. Thus, allogeneic hematopoietic stem cell transplantation (HSCT), as a post-remission therapy, should be considered. In three patients with Ph-chromosome-positive AML, we achieved complete remission with induction chemotherapy and the use of an imatinib cycle as an interim therapy. Subsequently, all patients received consolidation chemotherapy followed by imatinib cycles, bridging the time to allogeneic HSCT. All patients were successfully transplanted, and have been in excellent condition, with a median follow-up duration of 15 months (range, 2-25 months). We report on these cases and present the treatment strategy of induction chemotherapy, maintenance with imatinib mesylate, and final allogeneic HSCT as a representative paradigm for the treatment of Ph-chromosome-positive de novo AML.