Pretransplantation Therapy with Hypomethylating Agents in Patients with Myelodysplastic Syndromes Receiving Reduced-Intensity Conditioning Regimens

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Iron Overload during Follow-up after Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation in Patients with High-Risk Neuroblastoma

Multiple RBC transfusions inevitably lead to a state of iron overload before and after high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT). Nonetheless, iron status during post-SCT follow-up remains unknown. Therefore, we investigated post-SCT ferritin levels, factors contributing to its sustained levels, and organ functions affected by iron overload in 49 children with high-risk neuroblastoma who underwent tandem HDCT/autoSCT. Although serum ferritin levels gradually decreased during post-SCT follow-up, 47.7% of the patients maintained ferritin levels above 1,000 ng/mL at 1 yr after the second HDCT/autoSCT. These patients had higher serum creatinine (0.62 vs 0.47 mg/mL, P = 0.007) than their counterparts (< 1,000 ng/mL). Post-SCT transfusion amount corresponded to increased ferritin levels at 1 yr after the second HDCT/autoSCT (P < 0.001). A lower CD34+ cell count was associated with a greater need of RBC transfusion, which in turn led to a higher serum ferritin level at 1 yr after HDCT/autoSCT. The number of CD34+ cells transplanted was an independent factor for ferritin levels at 1 yr after the second HDCT/autoSCT (P = 0.019). Consequently, CD34+ cells should be transplanted as many as possible to prevent the sustained iron overload after tandem HDCT/autoSCT and consequent adverse effects

A Prognostic Score for Patients with Acute Leukemia or Myelodysplastic Syndromes Undergoing Allogeneic Stem Cell Transplantation

AbstractAllogeneic hematopoietic stem cell transplantation (SCT) has the potential to cure patients with acute leukemia or myelodysplastic syndromes (MDS), but a number of prognostic factors can influence the outcome of transplantation. At present, no transplantation-specific risk score exists for this patient population. We propose a simple scoring system for patients with acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), or MDS, based on a retrospective analysis of 445 patients undergoing SCT at our institution (divided into training and validation subsets). The score depends on 5 variables: age, disease, stage at transplantation, cytogenetics, and pretransplantation ferritin. It divides patients into 3 groups of comparable size, with 5-year overall survival (OS) of 56% (low risk), 22% (intermediate risk), and 5% (high risk). This prognostic score could be useful in making treatment decisions for individual patients, in stratifying patients entering clinical trials, and in adjusting transplantation outcomes across centers under the new federal reporting rules

Genetic characterization of Barbari goats using microsatellite markers

Genetic variation in Barbari goats, a highly prolific breed distributed widely in the northern part of India, known for better milk and meat quality, was studied as a part of genetic characterization and conservation. The genomic DNA from 50 unrelated Barbari goats were amplified via PCR with a panel of 21 microsatellite markers, and resolved through 6 per cent denaturing polyacrylamide gel electrophoresis followed by silver staining. The number of alleles ranged from 4 to 11, with allele sizes ranging from 88 to 220 bp. The distribution of allele frequencies was between 0.0104 and 0.5208. Polymorphism information content varied from 0.5563 to 0.8348. The population was not in Hardy-Weinberg equilibrium for all except two microsatellite loci (ILSTS044 and ILSTS060). The observed heterozygosity ranged from 0.8478 to 1.0000 while the expected heterozygosity ranged from 0.6208 to 0.8509. Based on the results of the present study, there is a good scope for exploiting the genetic variability in the Barbari goats for further improvement of performance

Allogeneic hematopoietic stem cell transplantation could improve survival of cytogenetically normal adult acute myeloid leukemia patients with DNMT3A mutations

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/115978/1/ajh24135.pd

Long-Term Follow-up of Reduced Intensity Allogeneic Stem Cell Transplantation for Chronic Lymphocytic Leukemia: Prognostic Model to Predict Outcome

CLL remains incurable with chemoimmunotherapy, and allogeneic hematopoietic stem cell transplantation (HSCT) offers potential for cure. We assessed the outcomes of 108 CLL patients undergoing first allogeneic HSCTs, 76 with reduced intensity (RIC) and 32 with myeloablative (MAC) conditioning between 1998 and 2009 at Dana-Farber Cancer Institute. With median follow-up 5.9 years in surviving patients, the 5 year OS for the entire cohort is 63% for RIC regimens and 49% for MAC regimens (p=0.18). The risk of death declined significantly starting in 2004 and we found that 5 year OS for HSCT between 2004–2009 was 83% for RIC regimens compared to 47% for MAC regimens (p=0.003). For RIC transplantation, we developed a prognostic model based on predictors of PFS, specifically remission status, LDH, comorbidity score and lymphocyte count, and found 5-year PFS 83% for score 0, 63% for score 1, 24% for score 2, and 6% for score >= 3 (p<0.0001). We conclude that RIC HSCT for CLL in the current era is associated with excellent long-term PFS and OS, and, as potentially curative therapy, should be considered early in the disease course of relapsed high-risk CLL patients

dynamics of immune cell reconstitution in allogeneic hematopoietic cell transplant patients receiving post transplant cyclophosphamide ptcy

In the setting of haploidentical hematopoietic cell transplantation (haplo-HCT), post-transplant cyclophosphamide (PTCy) selectively eliminates alloreactive T cells in-vivo, resulting in favorable graft versus host disease (GVHD), non-relapse mortality (NRM) and relapse outcomes. However, few studies have examined the impact of PTCy on immune reconstitution (IR). We quantified IR in 63 patients after haplo-HCT with PTCy, mofetil mycophenolate and tacrolimus (TAC) and compared results to 93 patients with 8/8 HLA matched related or unrelated donors (MD) receiving TAC, methotrexate and sirolimus for GVHD prophylaxis. Both groups received reduced intensity conditioning for hematologic malignancies. The median age of the Haplo-PTCy and MD cohorts was 55 and 57 years. Patient samples were analyzed using multi-color flow cytometry panels to characterize distinct lymphocyte populations. All IR values are expressed as median absolute cell count per μL. One month after HCT, recovery of all T cell subsets (CD3, CD4Tcon, Treg, CD8) was significantly reduced in the PTCy cohort compared to MD (Figure A, B, C). Recovery of CD4Tcon was also reduced at 2 and 3 months after PTCy (p NK cells were lower 1 month after PTCy (52.7 vs 91.1, p=0.08), but were significantly higher at 2, 3 and 6 months (153.4 vs 94.8, p=0.001, 153.7 vs 87.5, p=0.008, 180 vs 102, p=0.01, respectively, Figure D) compared to the MD cohort. Delayed NK cell recovery at 1 month after PTCy was due entirely to reduced numbers of CD56dim NK cells (Figure E). Subsequently recovery of CD56dim NK cells was similar in both cohorts. Recovery of CD56bright NK cells was significantly increased in the PTCy cohort (p Consistent with prior reports, 1 year cumulative incidence of extensive cGvHD was lower in the PTCy cohort compared to the MD cohort, 13% (5-26%, 95% CI) and 40% (30-50%, 95% CI) respectively, p=0.003, without increased NRM (p=0.28) or relapse (p=0.17). In summary, the effect of PTCy on IR was most pronounced 1 month after transplant with significantly delayed recovery of CD3, CD4Tcon, Treg, CD8 and CD56dim NK cells. Slow recovery of CD4Tcon persisted for 3 months and delayed recovery of Treg persisted for 1 year. Beginning 2 months after HCT, recovery of both CD56dim and CD56bright NK cells was more rapid in the PTCy cohort. Further studies will examine the effects of these differences in IR on clinical outcomes such as relapse, infections and GVHD

Allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission: systematic review and meta-analysis of prospective clinical trials.

The optimal treatment of acute myeloid leukemia (AML) in first complete remission (CR1) is uncertain. Current consensus, based on cytogenetic risk, recommends myeloablative allogeneic stem cell transplantation (SCT) for poor-risk but not for good-risk AML. Allogeneic SCT, autologous transplantation, and consolidation chemotherapy are considered of equivalent benefit for intermediate-risk AML