Azacitidine combined with interferon-α for pre-emptive treatment of AML/MDS after allogeneic peripheral blood stem cell transplantation: A prospective phase II study.

This prospective clinical study aimed to evaluate the efficacy and safety of the pre-emptive treatment modality of azacitidine in combination with interferon-α (IFN-α) in AML/MDS patients post-transplantation. Forty-seven patients aged 17-62 were enrolled with 14 patients having completed the planned 12 cycles. Following initiation, 72.3% responded positively after the first cycle, peaking at 77.2% by the fifth cycle. Notably, 24 patients maintained sustained responses throughout a median follow-up of 1050 days (range, 866-1234). Overall survival, leukaemia-free survival and event-free survival probabilities at 3 years were 69.5%, 60.4% and 35.7% respectively. Cumulative incidences of relapse and non-relapse mortality were 36.5% and 4.3% respectively. Multivariate analysis identified that receiving pre-emptive treatment for fewer than six cycles and the absence of chronic graft-versus-host disease after intervention was significantly associated with poorer clinical outcomes. The combination of azacitidine with IFN-α was well-tolerated with no observed severe myelotoxicity, and the majority of adverse events were reversible and manageable. In conclusion, the use of azacitidine in conjunction with IFN-α as pre-emptive therapy is a safe and effective treatment to prevent disease progression in AML/MDS patients with MRD positivity post-allo-HSCT.

Case report: Allogeneic stem cell transplantation for type B insulin resistance.

Type B insulin resistance (TBIR) is a rare, often fulminant form of insulin resistance caused by autoantibodies against the insulin receptor. If left untreated, its mortality is high. Various immunosuppressive regimens have shown efficacy, but treatment effects are variable and time-delayed, and drug-induced complications may arise. We report a patient with TBIR arising as a complication of Wiskott-Aldrich syndrome. Stable remission of TBIR was achieved through allogeneic peripheral blood stem cell transplantation (PBSCT) over a follow-up period of more than 1.5 years. We thus demonstrate that PBSCT can be considered a treatment option in TBIR where conventional immunosuppressive therapy is ineffective or contraindicated.

Aortitis after administration of pegfilgrastim to a healthy donor for peripheral blood stem cell collection.

A 45-year-old man who was a sibling donor for allogeneic peripheral blood stem cell transplantation (allo-PBSCT) was administered 7.2 mg of pegfilgrastim for stem cell collection. Peripheral blood stem cells were collected 4 days after administration of pegfilgrastim (Day 4) and 4.32 × 106 /kg of CD34-positive cells per recipient body weight were obtained. Fever of 38 ℃ or higher and left submandibular pain appeared on Day 6. Ultrasonography and contrast-enhanced computed tomography (CT) showed wall thickening of the carotid artery and the abdominal aorta. We carefully excluded the possibilities of cardiovascular and autoimmune diseases by thorough examination, and ultimately diagnosed pegfilgrastim-induced aortitis. The patient's fever resolved rapidly after treatment with prednisolone (PSL) 1 mg/kg. We began to taper PSL after eight days. Sixty-one days after starting PSL, we confirmed that abdominal aortic wall thickening had improved by contrast-enhanced CT. We continued to taper off PSL and stopped 141 days later with no relapse thereafter. This is the first case report of pegfilgrastim-induced aortitis in an allo-PBSCT donor. Careful monitoring is warranted when administering pegfilgrastim to donors even without past medical history.

A retrospective single-center analysis of G-CSF-mobilized donor lymphocyte infusion in hematologic malignancies after unmanipulated allogenic PBSCT.

To explore the efficacy and safety of G-SCF-mobilized donor lymphocyte infusion (DLI) for treatment of relapse of hematologic malignancies after allogeneic peripheral blood stem cell transplantation, we performed a retrospective analysis in a cohort of patients with morphologic (n = 36) or molecular (n = 22) relapse post transplantation. The 3-year post-DLI survival rates for therapeutic and preemptive DLI recipients were 16.7% and 33.3%, respectively. The occurrence of DLI-associated acute graft-versus-host disease predicted longer survival, whereas diagnosis of T cell acute lymphoblastic leukemia/lymphoma or myelodysplastic syndromes or early relapse after transplant (< 6 months) predicted shorter survival after therapeutic DLI. Cumulative incidence of progression to hematologic relapse and non-relapse mortality after preemptive DLI were 46.8% and 29.1%, respectively. Active disease prior to transplant and early molecular relapse after transplant (< 4 months) were the strongest predictors of non-relapse mortality after preemptive DLI. In conclusion, although therapeutic DLI had limited efficacy against T cell acute lymphoblastic leukemia/lymphoma or myelodysplastic syndromes or early post-transplant relapse, patients who developed DLI-associated acute graft-versus-host disease would benefit from this procedure in the setting of G-SCF-mobilized DLI. Furthermore, preemptive DLI could protect half of patients from hematologic relapse after transplantation with acceptable toxicity.

A pyruvate kinase deficiency child with novel PK-LR gene mutations was successfully cured by matched unrelated donor peripheral blood stem cell transplantation.

BACKGROUND: Pyruvate kinase deficiency (PKD) is an autosomal recessive disorder caused by a PK-LR gene mutation. Allogeneic hematopoietic cell transplantation (HCT) is an effective cure for PKD. However, the experience of applying HCT in PKD is limited. METHODS: We present a child with novel PK-LR gene mutations who was successfully cured by matched unrelated donor peripheral blood stem cell transplantation (MUD-PBSCT). RESULTS: A 4-year-old, male patient suffered severe hemolytic anemia and jaundice 5 h after birth. Gene sequencing showed that the pyruvate kinase-liver and RBC (PK-LR) gene had a nonsense mutation in exon 5: c.602G>A (p.W201X), and large deletions in exons 3-9. Both of them were novel pathogenic mutations of the PK-LR gene. After transplantation, the hemoglobin level became normal and the nonsense mutation was undetectable. Grade Ⅳ acute graft-versus-host disease (aGVHD) and extensive chronic graft-versus-host disease (cGVHD) occurred in the patient. However, the GVHD was controlled effectively. The patient is alive and has good quality of life 22 months post-transplant, but has mild oral lichen planus-like lesion. CONCLUSION: Gene sequencing contributes to the diagnosis of PKD. HCT is an effective method for curing PKD, but we should explore how to reduce severe GVHD.

Haematologic malignancies with unfavourable gene mutations benefit from donor lymphocyte infusion with/without decitabine for prophylaxis of relapse after allogeneic HSCT: A pilot study.

Relapse is the main cause of treatment failure for leukaemia patients with unfavourable gene mutations who receive allogeneic haematopoietic stem cell transplantation (allo-HSCT). There is no consensus on the indication of donor lymphocyte infusion (DLI) for prophylaxis of relapse after allo-HSCT. To evaluate the tolerance and efficacy of prophylactic DLI in patients with unfavourable gene mutations such as FLT3-ITD, TP53, ASXL1, DNMT3A or TET2, we performed a prospective, single-arm study. Prophylactic use of decitabine followed by DLI was planned in patients with TP53 or epigenetic modifier gene mutations. The prophylaxis was planned in 46 recipients: it was administered in 28 patients and it was not administered in 18 patients due to contraindications. No DLI-associated pancytopenia was observed. The cumulative incidences of grade II-IV and III-IV acute graft-versus-host disease (GVHD) at 100 days post-DLI were 25.8% and 11.0%, respectively. The rates of chronic GVHD, non-relapse mortality and relapse at 3 years post-DLI were 21.6%, 25.0% and 26.1%, respectively. The 3-year relapse-free survival and overall survival (OS) rates were 48.9% and 48.2%, respectively. Acute GVHD (HR: 2.30, p = 0.016) and relapse (HR: 2.46, p = 0.003) after DLI were independently associated with inferior OS. Data in the current study showed the feasibility of prophylactic DLI with/without decitabine in the early stage after allo-HSCT in patients with unfavourable gene mutations.

Risk factors and associations with clinical outcomes of cytomegalovirus reactivation after haploidentical versus matched-sibling unmanipulated PBSCT in patients with hematologic malignancies.

In allogeneic hematopoietic stem cell transplantation recipients, cytomegalovirus (CMV) infection can cause overt CMV-associated disease, which is a main cause of transplantation-associated mortality. CMV infection correlates closely with donor's type. We therefore examined whether risk factors of CMV reactivation and clinical endpoints in patients with hematologic malignancies after allogeneic peripheral blood stem cell transplantation (PBSCT) differed between using matched-sibling donors (MSD-SCT) and haploidentical donors (HID-SCT). In this retrospective cohort study, we enrolled in 200 consecutive patients received an unmanipulated G-CSF-mobilized allogeneic PBSCT. Ninety (45%) patients received MSD-SCT and 110 (55%) received HID-SCT. Quantitative PCR was used for monitoring of CMV reactivation after transplantation. One-year cumulative incidence of CMV DNAemia was 55.0%, ranging from 23.5% in MSD-SCT group to 81.0% in HID-SCT group (p < 0.001). Although univariate analyses showed that non-myeloid malignancies, disease in complete remission status at transplantation, pretreatment with antithymocyte globulin, HLA-haploidentical donors, male donors, previous Epstein-Barr virus DNAemia, and absolute lymphocyte count on day 30 < 0.6 × 109/L were respectively associated with CMV reactivation after transplantation in total cohort of recipients (all p < 0.05), haploidentical donors were found to be the only independent predictor in multivariate analyses (Hazard ratio = 6.4, p < 0.001). Furthermore, univariate analyses revealed that non-myeloid malignancies and previous Epstein-Barr virus DNAemia were respectively associated with CMV reactivation in MSD-SCT recipients, and female was associated with CMV reactivation in HID-SCT recipients (all p < 0.05). In HID-SCT recipients, but not MSD-SCT recipients, previous CMV DNAemia was associated with a lower cumulative incidence of acute graft-versus-host disease (49.2% vs. 72.6%, p < 0.001). CMV DNAemia did not play a role in the relapse rate, but it was strongly associated with an increased risk of non-relapse mortality either in total cohort of recipients (30.5% vs. 13.7%; p = 0.003) or in the HID-SCT subgroup (36.0% vs. 16.7%; p = 0.030). Relapse-free survival and overall survival in total cohort of recipients with CMV DNAemia were both inferior to those without CMV DNAemia (45.3% vs. 57.6% and 54.8% vs. 65.8%, respectively; both p < 0.05). However, in subgroup analysis according to donor's type, neither relapse-free survival nor overall survival was impacted by CMV status (both p > 0.05). This study addressed differences in incidence, risk factors, and associations with clinical outcomes of CMV reactivation after haploidentical versus matched-sibling PBSCT.

Reconstitution of NK cells expressing KIR3DL1 is associated with reduced NK cell activity and relapse of CML after allogeneic hematopoietic stem cell transplantation.

Although the prognosis of chronic myeloid leukemia (CML) in blastic crisis remains poor, some patients achieve long-term remission after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This may be attributable to graft-versus-leukemia (GVL) effects by donor lymphocytes, but their regulating mechanisms are unclear. Antitumor natural killer (NK) cell immunity is assumed to be important in CML, and we have previously shown that allelic polymorphisms of killer immunoglobulin-like receptors (KIRs) and histocompatibility leukocyte antigens (HLAs) are associated with the response of CML to tyrosine kinase inhibitors. Here, we report a case of CML in blastic phase who received HLA-matched but KIR3DL1 allelic-mismatched allo-HSCT. After transplant, decreased BCR-ABL transcript levels and enhanced NK cell activity were transiently observed. However, reconstitution of KIR3DL1-expressing NK cells occurred, which was associated with diminished NK cell activity and increased BCR-ABL. This case indicates the potential significance of KIR3DL1 in NK cell-mediated GVL activity following allo-HSCT. To the best of our knowledge, this is the first report to analyze the association between sequential KIR3DL1 expression and activity of NK cells after allo-HSCT. Selecting donors with KIR3DL1-null alleles may maintain competent GVL effects and provide improved outcomes in allo-HSCT for CML.

Risk factors and clinical outcomes of Epstein-Barr virus DNAemia and post-transplant lymphoproliferative disorders after haploidentical and matched-sibling PBSCT in patients with hematologic malignancies.

In allogeneic hematopoietic stem cell transplantation recipients, reactivation of Epstein-Barr virus (EBV) can cause post-transplantation lymphoproliferative disorder (PTLD), which may rapidly progress to multiorgan failure and even death. Development of EBV PTLD correlates very closely with use of anti-thymocyte globulin (ATG) and type of transplant. To assess the incidences and clinical features of EBV DNAemia and PTLD in the setting of stem cell transplantation using unmanipulated G-CSF-primed allogeneic peripheral blood stem cells as graft, we performed a retrospective analysis of stem cell transplantation from HLA-matched sibling donors (MSD-SCT, n = 90) or HLA-haploidentical related donors (HID-SCT, n = 110) in patients with hematological malignancies. All of HID-SCT recipients and 27.8% of MSD-SCT recipients received an ATG-containing conditioning regimen. One-year cumulative incidence of EBV DNAemia was 44.1%, ranging from 4.8% in MSD-SCT recipients not using ATG to 20.0% in MSD-SCT recipients using ATG, and 73.7% in HID-SCT recipients. Risk factors for EBV reactivation included use of ATG (p = 0.008), male donor (p = 0.034), and cytomegalovirus DNAemia (p < 0.001). One-year incidence of EBV PTLD was 11.9%, ranging from 1.8% in recipients of MSD-SCT not using ATG to 4.4% in recipients of MSD-SCT using ATG, and 23.5% in recipients of HID-SCT. Risk factors for PTLD after HID-SCT included in fludarabine-containing conditioning regimen (p = 0.010), cytomegalovirus DNAemia (p = 0.036), and patient's age < 40-yr (p = 0.032). Two-year non-relapse mortality was higher for patients with EBV DNAemia than those without EBV DNAemia (35.8% vs. 15.3%, p = 0.002). One-year relapse-free survival and overall survival among patients with PTLD were 40.2% and 44.9%, respectively, as opposed to 63.4% and 68.4% among patients without PTLD (both p < 0.05). In multivariate analyses, EBV DNAemia predicted a lower risk of relapse (p = 0.025), while PTLD was a marginally significant predictor of relapse (p = 0.092). This study identified patients at risk of EBV reactivation and PTLD after unmanipulated allogeneic peripheral blood stem cell transplantation.

Comparison of the safety and efficacy of prophylactic donor lymphocyte infusion after haploidentical versus matched-sibling PBSCT in very high-risk acute myeloid leukemia.

Donor lymphocyte infusion (DLI) might be used prophylactically to reduce relapse after allogeneic hematopoietic stem cell transplantation for very high-risk leukemia/lymphoma without effective targeted therapy. To compare the safety and efficacy of prophylactic DLI for prevention of relapse after allogeneic peripheral blood stem cell transplantation from haploidentical donors (HID-SCT) and matched-sibling donors (MSD-SCT) in patients with very high-risk acute myeloid leukemia (AML), we performed a retrospective analysis in a cohort of 21 HID-SCT and 13 MSD-SCT recipients, displaying similar baseline characteristics except for donor's gender distribution. Grade 2-4 acute graft-versus-host disease (GVHD) at 100-day post-DLI was higher in HID-SCT group than that in MSD-SCT group (59.5% vs. 30.8%, p = 0.05). The grade 3-4 acute GVHD (17.5% vs. 7.7%), 1-year chronic GVHD (36.6% vs. 33.2%), and severe chronic GVHD (15.3% vs. 27.3%) were not statistically significant different between groups. One-year non-relapse mortality was higher in HID-SCT group than that in MSD-SCT group with marginal significance (27.9% vs. 0.0%, p = 0.061). One-year relapse rate was not statistically significant different between HID-SCT group and MSD-SCT group (21.6% vs. 36.5%, p = 0.543). For HID-SCT recipients, 1-year relapse rate was lower in patients receiving prophylactic DLI than that in a control cohort of eight patients with same very high-risk features but not receiving prophylactic DLI (62.5% vs. 28.3%, p = 0.037). No statistically significant difference was observed in 1-year overall survival (OS, 55.1% vs. 83.9%, p = 0.325) and relapse-free survival (RFS, 50.1% vs. 74.0%, p = 0.419) rates between HID-SCT group and MSD-SCT group. In multivariate analyses, non-remission status prior to transplant, poor-risk gene mutations, and donor's age ≥ 48 years predicted a higher risk of relapse after DLI. Non-remission status prior to transplant predicted inferior OS and RFS. Patient's age ≥ 40 years also predicted an inferior OS. In conclusion, prophylactic DLI was very safe and efficient for reducing relapse in patients with very high-risk AML receiving MSD-SCT. In the recipients of HID-SCT, the application of prophylactic DLI could reduce the risk of relapse, although with a higher incidence of DLI-associated acute GVHD than those of MSD-SCT.

Outcomes of myeloablative peripheral blood stem cell transplantation for non-complete remission patients with relapsed/refractory peripheral T cell lymphomas.

There was limited information about the efficacy of myeloablative allogeneic peripheral blood stem cell transplantation (allo-PBSCT) in non-complete remission (non-CR) patients with relapsed/refractory peripheral T cell lymphomas (PTCLs). We conducted a retrospective study of 21 consecutive non-CR patients with relapsed/refractory PTCLs who received myeloablative allo-PBSCT between January 2008 and June 2016. The median follow-up of survivors was 46.5 months (range, 14-105 months). The estimated 3-year relapse rate was 24% (95% CI, 9 to 43%). The 3-year non-relapsed mortality rate was 24% (95% CI, 9 to 44%). Overall, the estimated 3-year overall survival was 47% (95% CI, 25 to 66%). And the estimated 3-year progression-free survival was 46% (95% CI, 24 to 66%). Specifically, eight patients failed to achieve a CR at the first evaluation 3 months after allo-PBSCT and received withdraw of immunosuppression. Five patients also received donor lymphocytes infusions. Five (5/8, 62.5%) patients responded subsequently to these interventions (complete = 4, partial = 1). Overall, ten patients were alive at our last follow-ups, and durable CR were achieved in nine patients without further therapy. Five (50%) of these ten alive patients experienced chronic graft-versus-host disease (GVHD). Our favorable clinical outcomes suggested myeloablative allo-PBSCT was a valid therapeutic option for non-CR patients with relapsed/refractory PTCLs. The sustained CR after immunotherapeutic intervention and high prevalence of chronic GVHD in alive patients provided evidence of graft versus T cell lymphoma effects.

Regulatory γδ T cells induced by G-CSF participate in acute graft-versus-host disease regulation in G-CSF-mobilized allogeneic peripheral blood stem cell transplantation.

BACKGROUND: The immunomodulatory effects of granulocyte colony-stimulating factor (G-CSF) on T cells result in a low incidence of acute graft-versus-host disease (aGVHD) in G-CSF-mobilized allogeneic peripheral blood stem cell transplantation (G-PBSCT). However, the exact mechanism remains unclear. Regulatory γδ T cells (γδTregs), characterized by the presence of TCRγδ and Foxp3, have aroused great concern in the maintenance of immune tolerance. We hypothesized that γδTregs might involve in the immunomodulatory effects of G-CSF mobilization. METHODS: The expression and immunomodulatory function of γδTreg subsets in peripheral blood of donors before and after G-CSF treatment in vivo and in vitro were evaluated by flow cytometry and CFSE assays. To investigate the effects of γδTregs on aGVHD, the association between γδTreg subsets in grafts and aGVHD in recipients was estimated. RESULTS: The proportions of Vδ1Tregs, CD27+Vδ1Tregs and CD25+Vδ1Tregs were significantly increased in peripheral blood after G-CSF treatment in vivo. γδTregs could be generated in vitro by stimulating with anti-TCRγδ in the presence of G-CSF. The immune phenotype, proliferation suppression function, and cytokine secretion of G-CSF-induced γδTregs were similar to that of transforming growth factor-ß (TGF-ß)-induced γδTregs. The clinical data demonstrated that the proportion of CD27+Vδ1Tregs in grafts was significantly lower in the patients who experienced aGVHD than in those who did not develop aGVHD (P = 0.028), and the proportions of other γδTreg subsets in grafts did not differ significantly between the two groups. The best cutoff value for CD27+Vδ1Treg proportion in grafts in prediction of aGVHD was 0.33%, with an area under the curve value of 0.725 (P = 0.043). Eight patients (26.7%) were classified as the low-CD27+Vδ1Treg group (< 0.33%), and 22 patients (73.3%) as the high-CD27+Vδ1Treg group (≥ 0.33%). The incidence of aGVHD was higher in the low-CD27+Vδ1Treg group than in the high-CD27+Vδ1Treg group (75.0% versus 22.7%, P = 0.028). CONCLUSIONS: G-CSF could induce the generation of γδTregs in vivo and in vitro, and γδTregs might participate in aGVHD regulation in G-PBSCT.

Serum microRNA181a: Correlates with the intracellular cytokine levels and a potential biomarker for acute graft-versus-host disease.

The aim of this study was to investigate the clinical relevance of lymphocyte-related serum miRNAs to the pathogenesis of acute graft-versus-host disease (aGVHD) and evaluate the predictive and prognosis value of miRNAs. Consecutive patients who received allogeneic peripheral blood stem cell transplantation (allo-PBSCT) in General Hospital of Jinan Military District were enrolled. aGVHD patients were diagnosed and graded clinically, and divided into the training set and the testing set. Blood samples were collected, total RNA was isolated, and RT-PCR was performed for miRNA expression (miR-181a-3p, miR-214-3p and miR-326). Intracellular cytokines levels were assayed by flow cytometry, and the disease specificity assay of miRNAs for aGVHD was detected. A total of 120 patients were admitted. Serum level of miR-181a in aGVHD patients was highly increased and associated with the severity of aGVHD, but not miR-214 and miR-326. Levels of cytokines including IL-2, IL-22, and IL-17a were positively correlated with miR-181a level, while serum IL-13 level was negatively correlated with miR-181a level in aGVHD patients. Moreover, increased miR-181a level was not detected in patients with acute rejection after kidney transplantation or sepsis patients. MiR-181a level was sensitively and specifically increased, especially in severe aGVHD patients. MiR-181a may be a potential biomarker for the identification, diagnosis, and prognosis of aGVHD patients.

Serum microRNA155 is increased in patients with acute graft-versus-host disease.

To explore the clinical relevance of three lymphocyte-related serum microRNAs (miR-155, miR-214, and miR-326) to the pathogenesis of graft-versus-host disease (GVHD), 64 subjects who received allogeneic peripheral blood stem cell transplantation (allo-PBSCT) were recruited in this study, of whom 19 subjects did not develop GVHD, 25 subjects were diagnosed with acute GVHD (aGVHD), and 20 subjects were diagnosed with chronic GVHD (cGVHD). Serum miRNAs were determined by real-time RT-PCR. Expression level of miRNAs and the expression signatures of miRNAs as a panel were analyzed among the three groups. The expression level of miR-214 and miR-326 showed no significant difference between GVHD and non-GVHD groups. However, miR-155 was significantly up-regulated in GVHD patients. There was a correlation between the level of miR-155 and the severity of aGVHD. Moreover, serum IFN-gamma, IL-17, and IL-9 levels were higher in aGVHD patients with high miR-155. In conclusion, the expression level of lymphocyte-related miR-155 in serum was significantly increased in aGVHD patients. The miR-155 may be considered as a potential targeted therapy for aGVHD patients.

Impact of Day +11 Methotrexate on the Incidence of Graft-versus-host Disease after HLA-identical Allogeneic Peripheral Blood Stem Cell Transplantation

BACKGROUND: Cyclosporine (CSA) plus 4 doses of methotrexate (MTX) is the commonly used regimen for GVHD prophylaxis. It has been previously found that the omission of the day +11 dose of MTX was associated with an increased risk of acute GVHD in the allogeneic BMT setting. However, little is known about its impact in the PBSCT setting. METHODS: Of the 68 patients, 30 patients (44%) received 4 doses of MTX (the MTX4 group), while 38 patients (56%) received less than 4 doses (the MTX3 group) because of their severe mucositis, hepatic dysfunction or renal failure. RESULTS: The cumulative incidence of acute GVHD was 60% in the MTX4 and 86% in the MTX3 group (P=0.038), while that of grade III and IV acute GVHD was 7% in the MTX4 group and 39% in the MTX3 group (P=0.017). Of the 61 patients evaluated for chronic GVHD, the cumulative incidence of chronic GVHD was 54% in the MTX4 group and 97% in the MTX3 group (P=0.001), while that of extensive chronic GVHD was 26% in the MTX4 group and 63% in the MTX3 group (P=0.004). There were no differences in the overall survival and the incidence of relapse between the two groups. On multivariate analyses, MTX3 was a poor prognostic factor in terms of acute GVHD and extensive chronic GVHD. CONCLUSION: This study suggested that omitting day +11 MTX and the clinical situation of the MTX3 group seemed to be associated with an increased incidence of acute and chronic GVHD. Accordingly, administration of day +11 MTX accompanied by active treatment of mucositis may prevent GVHD in the allogeneic PBSCT setting, but we need to conduct a large scale prospective study.

Single Center Experience of Allogeneic Peripheral Blood Stem Cell Transplantation for Acute Myeloid Leukemia / 대한혈액학회지

BACKGROUND: Recently, peripheral blood (PB) stem cells have been used widely for allogeneic stem cell transplantation (SCT), instead of bone marrow (BM). The current study analyzed the outcome of allogeneic PBSCT for the patients with acute myeloid leukemia (AML). METHODS: Twenty-nine patients with AML excluding AML M3 were included for the analysis. PB stem cells were collected from HLA-matched sibling donors mobilized with G-CSF with or without GM-CSF. RESULTS: Engraftment for neutrophil and platelet were achieved in a median 15.0 days and 14.0 days, respectively. The incidence of grade II~III acute graft versus host disease (GVHD) was 82.8% (24/29 patients), while of chronic GVHD 78.6% (22/28 patients, limited 11, extensive 11). During the median follow-up of 340 days (range, 86~1,603 days), 3 years overall survival and disease free survival was 51.4% and 40.0%, respectively. CONCLUSION: PB may be considered as a feasible source of allogeneic SCT for patients with AML.

Clinical Outcomes according to Transplanted CD34+ Cell Dose in Allogeneic Peripheral Blood Stem Cell Transplantation / 대한혈액학회지

BACKGROUND: Recently, allogeneic peripheral blood stem cell transplantation (Allo-PBSCT) instead of bone marrow transplantation (BMT) has been widely used with the benefits of an earlier recovery of blood cells and a lower incidence of graft failure because of higher CD34+ cell dose. However, recent studies suggested that the higher dose of CD34+ cells might be related to the lower survival and the higher morbidity due to chronic graft versus host disease (cGVHD). We have analyzed the impact of transplanted CD34+ cell dose on clinical outcomes in unmanipulated allo-PBSCT from HLA identical siblings. METHODS: Thirty-one consecutive adult patients with hematological diseases, who survived until at least day 90 after allo-PBSCT and were evaluable for cGVHD, were included. Peripheral blood stem cells were collected from HLA-matched sibling donors mobilized with G-CSF and/or GM-CSF. The patients were classified into a "low" or "high" CD34+ cell dose group based on whether they received less or more than a median CD34+ cell dose of 11.17X10(6)/kg, respectively. RESULTS: The median CD34+ cell dose was 11.17X10(6)/kg (range, 4.12-58.80X10(6)/kg). Acute GVHD (grade II-IV) appeared in 24 patients (77.4%) and extensive cGVHD in 14 patients (45.2%). During the follow-up (median: 340 days, range: 111-1263 days), relapses were observed in 12 patients (38.7%) and 19 patients are still alive. There was a significant difference in the incidence of extensive cGVHD (20.0% vs 68.8%, P=0.011) and relapse (60.0% vs 18.8%, P=0.029) between low and high CD34+ cell dose groups, but no difference of the incidence of acute GVHD or the days of engraftments between the two groups. The estimated survival rate was significantly different between the two groups (3 year survival rate, 31.5% vs 79.8%, P=0.022) and the patients with extensive cGVHD showed a higher survival rate than those without extensive cGVHD (55.6% vs 12.5%, P=0.013). CONCLUSION: Better survival rate was observed in high CD34+ cell dose group for alloPBSCT, while a higher incidence of extensive cGVHD was noted. The optimal dose of CD34+ cells need to be determined to minimize the morbidity related to cGVHD and to improve survival.

Allogeneic Peripheral Blood Stem Cell Transplantation from An HLA-identical Sibling Donor in Children / 대한소아혈액종양학회지

PURPOSE: G-CSF-mobilized peripheral blood is one of the sources of allogeneic hematopoietic stem cells. We report our experiences on allogeneic peripheral blood stem cell transplantation (allo-PBSCT) from an HLA-identical sibling donor in children. METHODS: From August 1998 to January 2003, 8 patients underwent allo-PBSCT. Median age of recipients and donors were 4 yr 10 mo (range 3 yr 2 mo 15 yr) and 5 yr 1 mo (range 1 yr 11 mo 19 yr 8 mo), respectively. Seven patients (3 ALL, 2 neuroblastomas, 1 AML, 1 Gaucher disease) had failed from previous allogeneic or autologous transplant and 1 patient had refractory acute biphenotypic leukemia. Only 2 patients were in complete remission at allo-PBSCT. G-CSF 10mug/kg/day was injected subcutaneously to the donor for 5 days and large volume leukapheresis was performed on 4th and 5th days. RESULTS: Median number of CD34 and CD3 cells infused was 18.55 106 (range 9.47 84.76) /kg and 8.26 108 (range 0.88 24.58) /kg, respectively. All patients achieved ANC > 0.5 109/L after a median of 9 days and 6 patients eventually achieved platelet engraftment. There was no grade II-IV acute GVHD but limited chronic GVHD developed in 6 evaluable patients. There was no CMV antigenemia. Three patients died from either transplant-related mortality (n=2) or relapse (n=1). The remaining 5 patients are alive disease-free for 7, 8, 15, 16, and 19 months from allo-PBSCT, respectively. CONCLUSION: Our results suggest that mega-dose allo-PBSCT from an HLA-identical sibling donor is expected to improve transplant outcome especially in very high risk pediatric patients.

NONMYELOABLATIVE ALLOGENEIC PERIPHERAL BLOOD STEM CELL TRANSPLANTATION FROM UNRELATED DONOR FOR TREATMENT OF ACUTE LYMPHOBLASTIC LEUKEMIA:THE FIRST CASE REPORT / 解放军医学杂志

The purpose of this study was to investigate the clinical efficacy against acute leukemia by transplantation of nonmyeloablative allogeneic peripheral blood stem cells from unrelated donor (URD NAPBSCT). One patient with acute lymphoblastic leukemia received URD NAPBSCT in our hospital. The donor cells were full engafted, and grade Ⅱ skin aGVHD and interstitial pneumonia were developed. The results showed that URD NAPBSCT is an effective new method for the treatment of acute leukemia.

A Case of DNA Chimerism Analysis as a Marker of Donor Lymphocyte Infusion / 대한혈액학회지

Donor lymphocyte infusion (DLI) has some benefit effects as graft-versus-leukemia effect, reducing the relapse of leukemia and inducing of a complete remission. But it has also a graft-versus-host-disease (GVHD) effect. So it is required a proper marker test when DLI is performing. The DNA chimerism analysis can be a marker test in DLI. Variable number of tandem repeats (VNTR) are highly polymorphic DNA markers in the human genomic DNA and used as primers of DNA chimerism analysis. A 43-year-old male who had been diagnosed acute myelogenous leukemia was transplanted with allogeneic peripheral blood stem cells. The initial chimerism analysis showed complete chimerism but it changed to mixed chimerism after 7 months of transplantation. We predicted the relapse of leukemia and performed DLI. The patient could obtain the complete chimerism after DLI. We report a case of chimerism analysis which was useful to predict the relapse of leukemia and perform the DLI.