PURPOSE: To investigate the efficacy and safety of umbilical cord blood (UCB) infusion (UCBI) plus immunosuppressive therapy (IST) treatment in comparison to IST treatment, as well as predictive factors for clinical responses, in severe aplastic anemia (SAA) patients. MATERIALS AND METHODS: Totally, 93 patients with SAA were enrolled in this cohort study. In the IST group, rabbit antithymocyte globulin (r-ATG) combined with cyclosporine A (CsA) was administered, while in the IST+UBCI group, r-ATG, CsA, and UCB were used. RESULTS: After 6 months of treatment, UCBI+IST achieved a higher complete response (CR) rate (p=0.002) and an elevated overall response rate (ORR) (p=0.004), compared to IST. Regarding hematopoietic recovery at month 6, platelet responses in the UCBI+IST group were better than those in the IST group (p=0.002), and UCBI+IST treatment facilitated increasing trends in absolute neutrophil count (ANC) response (p=0.056). Kaplan-Meier curves illuminated UCBI+IST achieved faster ANC response (p < 0.001) and platelet response (p < 0.001), compared with IST therapy. There was no difference in overall survival (OS) between the two groups (p=0.620). Furthermore, logistic regression analysis demonstrated that UCBI+IST was an independent predicting factor for both CR (p=0.001) and ORR (p < 0.001), compared to IST; meanwhile, very severe aplastic anemia (VSAA) and ANC could predict clinical responses as well. However, Cox proportional hazard regression indicated that VSAA (p=0.003), but not UCBI+IST, affected OS. Safety profiles showed that UCBI+IST therapy did not elevate adverse events, compared with IST treatment. CONCLUSION: UCBI+IST achieved better clinical responses and hematopoietic recovery than IST, and was well tolerated in SAA patients.
Anemia, Aplastic* ; Antilymphocyte Serum ; Blood Platelets ; Cohort Studies ; Cyclosporine ; Fetal Blood* ; Humans ; Logistic Models ; Neutrophils ; Umbilical Cord*

Heavy proteinuria in the nephrotic range is an uncommon, often unrecognized manifestation of graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation. A few isolated case reports have been published in the Korean literature involving a small number of patients who developed membranous nephropathy as GVHD after peripheral blood stem cell transplantation (PBSCT). A 17-year-old female was diagnosed with non-Hodgkin's lymphoma. Following remission, she underwent allogeneic PBSCT. Shortly thereafter, she developed acute GVHD, which was managed by medical therapy with prednisolone and cyclosporine. Approximately 13 months following PBSCT, the patient developed proteinuria without peripheral edema. Pulsed steroid therapy was initiated three times, but her condition did not improve. Twenty months after PBSCT, she developed nephrotic range proteinuria. A renal biopsy was performed, and the diagnosis was histologically consistent with membranous nephropathy. Because the response to steroids was not satisfactory, the dose of cyclosporine was increased. Approximately 3 months after renal biopsy, the proteinuria disappeared. Given the recent increase in the incidence of GVHD-mediated renal disease, in particular, renal biopsy is indispensable to the diagnosis of nephropathy and to the prevention of disease progression.
Adolescent ; Biopsy ; Cyclosporine ; Diagnosis ; Disease Progression ; Edema ; Female ; Glomerulonephritis, Membranous* ; Graft vs Host Disease* ; Hematopoietic Stem Cell Transplantation ; Humans ; Incidence ; Lymphoma, Non-Hodgkin ; Peripheral Blood Stem Cell Transplantation ; Prednisolone ; Proteinuria ; Stem Cells* ; Steroids

BACKGROUND: Psoriasis is a chronic recurrent disease requiring long-term treatment; therefore, special attention is warranted when prescribing cyclosporine A (CsA) for patients diagnosed with psoriasis. Various forms of maintenance therapy have been suggested to reduce the incidence of adverse events associated with CsA use. OBJECTIVE: We aimed to compare the efficacy and safety of the three aforementioned CsA therapies for management of patients with psoriasis. METHODS: Patients fulfilling our selection criteria were selected for the study. CsA therapy (2.5∼5 mg/kg/day) was administered for 12 weeks, and patients who showed remission following this treatment were administered maintenance therapy. Patients with successful induction of response were randomly assigned to three treatment groups. Group A was the continuous regimen group (2∼3 mg/kg/day). Group B was the pulsed regimen group (4 mg/kg/day for 4 days, 3 days of discontinuation). Group C was the weekend regimen group (5 mg/kg/day for 2 days, 5 days of discontinuation). Patients were followed up on an outpatient basis at 4-week intervals to monitor treatment effects. RESULTS: In each group, the Psoriasis Area and Severity Index (PASI) and body surface area (BSA) values decreased in a similar fashion from visit 1 to visit 4 and at the time of the final visit 7. In each group, dermatology life quality index (DLQI) values showed statistically significant differences between pre- and post-treatment states; however, no inter-group differences were observed. Although adverse events such as elevated blood pressure and serum creatinine levels were slightly higher in the intermittent group, there was no significant inter-group difference. CONCLUSION: The pulsed regimen did not show a major difference in treatment effects compared to the everyday use group. We propose that the patient's age, presence of underlying diseases, lifestyle patterns, and convenience of use should be considered while determining the type of regimen administered to a patient.
Blood Pressure ; Body Surface Area ; Creatinine ; Cyclosporine* ; Dermatology ; Humans ; Incidence ; Life Style ; Outpatients ; Patient Selection ; Psoriasis* ; Quality of Life

BACKGROUND: Tacrolimus (Tac) can cause impaired insulin release and dyslipidemia, and may affect the development of post-transplant diabetes mellitus. However, these effects on insulin sensitivity and lipid profile have not been compared in renal transplant recipients receiving traditional twice-daily tacrolimus (TacBID) or cyclosporine and those receiving once-daily prolonged release formulation of tacrolimus (TacOD). METHODS: We conducted an observational prospective study of 15 stable non-diabetic renal transplant recipients to observe the changes in insulin sensitivity and lipid profiles for 1 year at a tertiary hospital. We evaluated the levels of hemoglobin A1c, total cholesterol, high density lipoprotein, low density lipoprotein, triglycerides, apolipoprotein A1, apolipoprotein B, serum creatinine, fasting plasma glucose, fasting insulin, homeostatic model assessment of β-cell (HOMA-β) and HOMA-insulin resistance index at baseline and at 2 and 4 months. To analyze differences in parameters, we conducted a Wilcoxon rank sum test and general linear model (GLM)-repeated measures analysis of variance (ANOVA) in both groups (cyclosporine to TacOD conversion group/TacBID to TacOD conversion group). RESULTS: At baseline, parameters did not differ between groups. GLM-repeated measures ANOVA revealed no change in insulin sensitivity or lipid profile after conversion at baseline or at 2 and 4 months. There were no complications after conversion from standard TacBID or cyclosporine to TacOD. CONCLUSIONS: There was no change in insulin sensitivity or lipid profile in renal transplant recipients. Any conversion from TacBID to TacOD should be performed in a controlled manner under close surveillance.
Apolipoprotein A-I ; Apolipoproteins ; Blood Glucose ; Cholesterol ; Creatinine ; Cyclosporine* ; Diabetes Mellitus ; Dyslipidemias ; Fasting ; Insulin Resistance* ; Insulin* ; Kidney Transplantation ; Linear Models ; Lipoproteins ; Prospective Studies ; Tacrolimus* ; Tertiary Care Centers ; Transplant Recipients* ; Triglycerides

The treatment of chronic spontaneous urticaria begins with antihistamines; however, the dose required typically exceeds that recommended for allergic rhinitis. Second-generation, relatively non-sedating H1-receptor blockers are typically employed up to 4 times a day. First-generation antihistamines, such as hydroxyzine or diphenhydramine (Atarax or Benadryl), were employed similarly in the past. Should high-dose antihistamines fail to control symptoms (at least 50%), omalizumab at 300 mg/month is the next step. This is effective in 70% of antihistamine-refractory patients. H₂-receptor blockers and leukotriene antagonists are no longer recommended; they add little and the literature does not support significant efficacy. For those patients who are unresponsive to both antihistamines and omalizumab, cyclosporine is recommended next. This is similarly effective in 65%–70% of patients; however, care is needed regarding possible side-effects on blood pressure and renal function. Corticosteroids should not be employed chronically due to cumulative toxicity that is dose and time dependent. Brief courses of steroid e.g., 3–10 days can be employed for severe exacerbations, but should be an infrequent occurrence. Finally, other agents, such as dapsone or sulfasalazine, can be tried for those patients unresponsive to antihistamines, omalizumab, and cyclosporine.
Adrenal Cortex Hormones ; Blood Pressure ; Cyclosporine ; Dapsone ; Diphenhydramine ; Histamine Antagonists ; Humans ; Hydroxyzine ; Leukotriene Antagonists ; Omalizumab ; Rhinitis, Allergic ; Sulfasalazine ; Urticaria*

OBJECTIVETo analyze early hematopoietic response and long-term survival of very severe aplastic anemia (VSAA) patients with different absolute neutrophil counts (ANC) after frontline immnunosuppressive therapy (IST).

METHODSClinical data and outcome of 145 VSAA patients treated with rabbit antithymocyte globulin combined with cyclosporine were retrospectively analyzed. Hematopoietic responses to IST and long-term survival were statistically analyzed for VSAA patients in different ANC subgroups.

RESULTSPre-IST ANC=0.05×10(9)/L acted as the best cutoff level to predict IST response at 3, 6 months. For 145 VSAA patients, early death rate was 13.4% (11/82) vs 1.6% (1/63), respectively, in the ANC≤0.05×10(9)/L group and ANC>0.05×10(9)/L group (P<0.05). Hematopoietic response rates to IST was 22.0% vs 54.0% (P=0.000) at 3 months, 34.1% vs 63.5% (P=0.000) at 6 months; the overall five-year survival rate was only (62.5±5.4) % vs (91.4±3.7) % (P=0.000) and five-year event-free survival rate was (42.3±5.5) % vs (63.1±6.5) % (P=0.003), respectively, in the ANC≤0.05×10(9)/L group and ANC>0.05×10(9)/L group.

CONCLUSIONVSAA patients with extremely low ANC (≤0.05×10(9)/L) had high early death rate and with very low response rate to frontline IST and poor survival, so it is urgent to seek for the alternative frontline therapy that will bring faster and better outcome for these patients.

Anemia, Aplastic ; blood ; drug therapy ; Animals ; Antilymphocyte Serum ; therapeutic use ; Cyclosporine ; therapeutic use ; Disease-Free Survival ; Humans ; Immunosuppressive Agents ; therapeutic use ; Leukocyte Count ; Neutrophils ; cytology ; Rabbits ; Retrospective Studies ; Survival Rate ; Treatment Outcome

BACKGROUND/AIMS: The relationship between patient survival and biopsy-proven acute rejection (BPAR) in liver transplant recipients with hepatitis C remains unclear. The aims of this study were to compare the characteristics of patients with and without BPAR and to identify risk factors for BPAR. METHODS: We retrospectively reviewed the records of 169 HCV-RNA-positive patients who underwent LT at three centers. RESULTS: BPAR occurred in 39 (23.1%) of the HCV-RNA-positive recipients after LT. The 1-, 3-, and 5-year survival rates were 92.1%, 90.3%, and 88.5%, respectively, in patients without BPAR, and 75.7%, 63.4%, and 58.9% in patients with BPAR (P<0.001). Multivariate analyses showed that BPAR was associated with the non-use of basiliximab and tacrolimus and the use of cyclosporin in LT recipients with HCV RNA-positive. CONCLUSION: The results of the present study suggest that the immunosuppression status of HCV-RNA-positive LT recipients should be carefully determined in order to prevent BPAR and to improve patient survival.
Antibodies, Monoclonal/therapeutic use ; Biopsy ; Cyclosporine/therapeutic use ; Drug Therapy, Combination ; Genotype ; Graft Rejection/mortality/*prevention & control ; Hepacivirus/genetics/isolation & purification ; Hepatitis C/drug therapy/*virology ; Humans ; Immunosuppressive Agents/*therapeutic use ; *Liver Transplantation/adverse effects ; Polymerase Chain Reaction ; RNA, Viral/blood ; Recombinant Fusion Proteins/therapeutic use ; Recurrence ; Retrospective Studies ; Survival Rate ; Tacrolimus/therapeutic use

OBJECTIVETo retrospectively study the impacts of ABO incompatibility on early outcome after single unit unrelated cord blood transplantation（UCBT）, such as cumulative incidence of engraftment, incidence of acute graft- versus- host disease （aGVHD） and 180- day transplant- related mortality（TRM）.

METHODS208 patients underwent single unit UCBT from April 2008 to October 2014 were analyzed, included 99 ABO- identical, 60 minor, 38 major and 11 bidirectional ABO- incompatible recipients. All the patients received intensified myeloablative conditioning, and a combination of cyclosporine A and mycophenolate mofetil was given for GVHD prophylaxis.

RESULTSCumulative incidences of neutrophil engraftment, platelet recovery, erythroid lineage reconstitution, Ⅱ-Ⅳ aGVHD, Ⅲ-Ⅳ aGVHD and 180- day TRM showed no significant difference among the patients receiving ABOidentical, minor, major, and bidirectional UCBT（all P>0.05, respectively）. What's more, none of the patients developed pure red- cell aplasia（PRCA）after UCBT. Group A donor and a group O recipient patients didn't appeared to influence the clinical results when compared with others（all P>0.05, respectively）.

CONCLUSIONPatients receive ABO- incompatible UCBT may not develop PRCA. The presence of ABO- incompatibility did not influence the hematopoietic reconstitution, the incidence of aGVHD and 180-day TRM in this cohort. There is not support for the need to regard ABO-compatibility as an UCB-graft selection criterion.

ABO Blood-Group System ; Blood Group Incompatibility ; Cord Blood Stem Cell Transplantation ; adverse effects ; Cyclosporine ; therapeutic use ; Graft vs Host Disease ; complications ; Humans ; Mycophenolic Acid ; analogs & derivatives ; therapeutic use ; Red-Cell Aplasia, Pure ; complications ; Retrospective Studies ; Tissue Donors ; Transplantation, Homologous

OBJECTIVETo investigate the long- term outcome of cyclosporin A (CsA) combined with thalidomide regime for Chinese patients with IPSS low/intermediate- 1 myelodysplastic syndromes (MDS) without del（5q）and the predictive variables which could impact the response to the therapy.

METHODSSeventy-six MDS patients who were treated with these drugs at a single institute in China were retrospectively analyzed. The polymorphism of cereblon gene, rs1672753, was detected in patients of this cohort by PCR and direct sequencing.

RESULTSA total of 53% of patients showed hematological improvement（HI）to the therapy. Thirty-one patients（31/73, 43%）achieved erythrocyte response（HI-E）; 15 patients（15/50, 30%）achieved neutrophil response（HI-N); 18 patients（18/58, 31%）achieved platelet response（HI-P). Twenty-seven of the 50 patients（46%）who were dependent on red blood cell transfusion achieved HI- E and became independent of transfusion. The median duration of response among the responders was 22 months (range, 1- 131 + months). Bone marrow blasts ≤2% was the only factor associated with longer response duration in univariate analysis （P=0.010）. There was no significant difference between the two groups of celeblon gene rs1672753 polymorphism either on the response rate or the response duration. The median survival of 67 patients without stem cell transplantation was 82 months. In multivariate analyses, factors significantly correlated with survival were IPSS-R（HR=3.461, 95%CI 1.126-10.639, P=0.030), age ≥ 60 y（HR=4.120, 95%CI 1.070-15.867, P=0.040）and HI-N（HR=7.733, 95%CI 1.007-59.396, P=0.049).

CONCLUSIONCsA combined with thalidomide regime could improve the anemia symptom in low/int-1 risk MDS patients without del（5q）. The predictive value of cereblon gene polymorphism, rs1672753, could not be verified in this study.

Anemia ; Blood Platelets ; Blood Transfusion ; Bone Marrow ; China ; Cyclosporine ; therapeutic use ; Erythrocytes ; Humans ; Myelodysplastic Syndromes ; classification ; drug therapy ; Neutrophils ; Peptide Hydrolases ; metabolism ; Remission Induction ; Retrospective Studies ; Thalidomide ; therapeutic use ; Treatment Outcome

OBJECTIVETo evaluate the therapeutic efficacy and related risk factors of acute myelogenous leukemia （AML） patients treated with unrelated cord blood transplantation （UCBT）.

METHODSA retrospective analysis was performed on the clinical data of 58 AML patients that consisted of 1 case of M0, 1 case M1, 35 cases M2, 3 cases M4, 14 cases M5, 3 cases M6, and 1 case acute mixed leukemia, respectively. Of them, 1 case AML secondary to myelodysplastic syndrome, and 36 in first complete remission （CR1）, 14 in second complele remission （CR2）, 8 in non- remission （NR）, 43 cases were refractory or high-risk patients（70.1%）. The median age was 14.5 years with the median weight of 45 kg, 49 patients received sUCBT and 9 dUCBT. All the patients conditioned with intensified myeloablative regimen and received a combination of Cyclosporine A（CsA）and mycophenolate mofetil（MMF）to prevent graft- versus- host disease（GVHD）.

RESULTS56 out of 58 patients achieved engraftment with implantation rate 96.6%. The median time of ANC≥0.5×10⁹/L was 17（12-37）days, and that of PLT≥20× 109/L 33（17-140）days respectively. 24 cases developed acute GVHD（aGVHD）, the incidence rate of grade Ⅱ to Ⅳ aGVHD was 30.4%. The chronic GVHD（cGVHD）was occured in 7 patients of the 49 evaluable patients, all were limited. The estimated 3-year overall survival（OS）and disease-free survival （DFS）were（60.3±6.4）% and（60.1±6.5）% respectively. And the cumulative incidences of 3-year nonrelapse mortality（NRM）and relapse were 33.3% and 9.1% respectively. The 3- year OS rates of AML patients were（66.0 ± 6.7）% for CR and（25.0 ± 15.3）% for NR, differences were statistical significance.

CONCLUSIONFor AML patients, UCBT was conducive to improve outcome with lower incidences of cGVHD and relapse, the patients after transplantation could obtain high quality of life.

Acute Disease ; Adolescent ; Cyclosporine ; Disease-Free Survival ; Fetal Blood ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Incidence ; Leukemia, Myeloid, Acute ; Mycophenolic Acid ; analogs & derivatives ; Quality of Life ; Recurrence ; Remission Induction ; Retrospective Studies