ABSTRACT
Interferon-α (IFN-α) inhibits tumor growth and mimics graft-versus-leukemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In the current case-control study, we compared treatment responses in acute leukemia patients with relapse tendency post-allo-HSCT receiving preemptive IFN-α after withdrawal of immunosuppressants (n = 31) vs. receiving no IFN-α (n = 67). In the IFN-α group, 25 patients responded to the treatment without progressing to hematological relapse. In the non-IFN-α group, only 22 patients responded to the treatment. The response rate differed significantly (80.6 vs. 32.8%, P < 0.001). The 2-year cumulative incidence of relapse was 31.6 and 61.2% in the IFN-α and the non-IFN groups, respectively (P = 0.006). The 2-year leukemia-free survival and overall survival rate was 57.4 vs. 28.4% (P < 0.001) and 67.6 vs. 32.9% (P = 0.001), respectively. Among the 31 patients in the IFN-α group, 18 patients (58.1%) developed graft-versus-host disease (GVHD): 6 acute and 12 limited chronic GVHD. Patients who developed GVHD had higher treatment response rate than patients without GVHD (88.9 vs. 53.8%, P = 0.022). In conclusion, preemptive IFN-α therapy is a safe and effective treatment to prevent disease progression in high-risk patients with relapse tendency post-allo-HSCT.
Subject(s)
Hematopoietic Stem Cell Transplantation , Interferon-alpha/administration & dosage , Leukemia , Acute Disease , Adolescent , Adult , Allografts , Child , Chronic Disease , Disease-Free Survival , Female , Graft vs Host Disease/etiology , Graft vs Host Disease/mortality , Graft vs Host Disease/pathology , Humans , Leukemia/mortality , Leukemia/pathology , Leukemia/therapy , Male , Middle Aged , Recurrence , Survival RateABSTRACT
This study was purposed to investigate the engraftment, graft-versus-host disease (GVHD), transplantation related mortality (TRM), relapse and survival in hematologic patients received unrelated umbilical cord blood transplantation (UCBT). A total of 25 patients with hematological disease underwent UCBT, including 8 pediatric and 17 young adult patients. Among them 3 cases received single unit of UCBT and 22 cases received double units of UCBT. For donor/recipients human leukocyte antigen (HLA) matching: HLA 6/6 loci matched in 9 cases, HLA 4-5/6 loci matched in 16 cases. There were 19 patients with hematologic malignancies, including 3 cases in the period of disease progression and 6 cases of non-hematologic malignancies. Conditioning regimens were TBI/Cy ± Flu ± ATG or BuCy ± Flu ± ATG for 21 patients and Cy+Flu+ATG for 4 patients. For prophylaxis of acute graft-versus-host disease (aGVHD) the regimen of cyclosporine (CsA) as dominant drug was used. The results showed that among 16 patients (80.0%) achieved engraftment, 20 patients survived for more than 42 d after transplantation. The cumulative neutrophil recovery rate on day 42 after transplant was 64.0%, with a median time of 17.0 d;the cumulative platelet recovery rate on day 100 after transplant was 60.0 %, with a median time of 35.0 d. The cumulative rate of grade II-IV and III-IV aGVHD after transplantation 100 d was 44.0% and 30.7%, respectively. Until the end of the follow-up, the cumulative rate of TRM was 54.3%. For all the patients, overall survival rate was 42.7%. Out of 17 evaluable patients with hematologic malignancies 7 cases (41.2%) survived to date, and only 1 case relapsed, so event-free survival rate was 35.3%. Out of 5 evaluable patients with non-hematologic malignancies, 4 patients survived and 2 patients were in stable engraftment state, 2 cases with autologous hematopoietic recovery. Among 3 cases of hematologic malignancies at advanced stage, only 1 case survived to date. It is concluded that HLA-4-6/6 loci matched UCBT is an effective option to treat hematological diseases. Double cord blood transplantation (dUCBT) can overcome the disadvantage of insufficient cells of single cord blood UCBT to treat overweight children and adult.
Subject(s)
Cord Blood Stem Cell Transplantation/methods , Hematologic Diseases/therapy , Adolescent , Adult , Child , Child, Preschool , Female , Fetal Blood , Graft vs Host Disease , Histocompatibility Testing , Humans , Male , Survival Rate , Young AdultABSTRACT
OBJECTIVE: To evaluate the safety and efficacy of umbilical cord-derived mesenchymal stem cells (MSCs) infusion in patients with steroid-resistant severe acute graft-versus-host disease (aGVHD). METHODS: A total of 19 patients with steroid-resistant severe aGVHD received MSCs infusion treatment. The treatment response, transplantation-related mortality, events associated with infusion and relapse rate were analyzed. RESULTS: Two patients with grade II, 5 patients with grade III and 12 patients with grade IV aGVHD received a total of 58 infusions of MSCs. The mean total dose of MSCs was 2.13 (range 0.60 - 7.20)×10(6) cells per kg bodyweight. Seven patients received one infusion, 2 patients received two infusions, and 10 patients received three or more infusions. Eleven patients had a complete response and 4 had a partial response and 4 had no response. No patients had side-effects during or immediately after infusions, and no MSCs related tumorigenesis was detected to date. Eleven patients survived and 8 died, 4 for aGVHD, 1 for infection and 2 for aGVHD with concomitant infection and 1 for underlying leukemia relapse. The cell viability of freshly prepared MSCs is 93% (92% - 95%) by trypan blue staining. The cell viability of programmatically frozen and thawed MSCs is 72% (70% - 74%). CONCLUSION: Infusion of umbilical cord-derived MSCs expanded in vitro is an effective therapy for patients with steroid-resistant severe aGVHD without negative impact on relapse. Freshly prepared MSCs are superior to frozen and thawed cells in terms of cell viability.
