ABSTRACT
Immune reconstitution after hematopoietic stem cell transplantation (HSCT) is a complex and extremely variable process. The Ikaros transcription factor plays an important role in hematopoiesis in several cell lines, especially in the lymphoid lineage. We hypothesized that Ikaros might influence immune reconstitution, and consequently, the risk of opportunistic infections, relapse, and graft versus host disease (GVHD). Samples were collected from the graft and from the peripheral blood (PB) of the recipients 3 weeks after neutrophil recovery. Real-time polymerase chain reaction (RT-PCR) was performed to analyze the absolute and relative Ikaros expression. Patients were divided into two groups, according to Ikaros expression in the graft and in the recipients' PB based on the ROC curves for moderate/severe cGVHD. A cutoff of 1.48 was used for Ikaros expression in the graft, and a cutoff of 0.79 was used for Ikaros expression in the recipients' PB. Sixty-six patients were included in this study. Median age of patients was 52 years (range 16-80 years), 55% of them were male, and 58% of them had acute leukemia. Median follow-up period was 18 months (range 10-43 months). There was no association between Ikaros expression and the risk of acute GVHD, relapse, or mortality. However, a significant association was observed with the risk of chronic GVHD. Higher Ikaros expression in the graft was associated with a significantly higher cumulative incidence (CI) of moderate/severe chronic GVHD according to the National Institute of Health (NIH) classification at two years (54% vs. 15% for patients with lower expression, P = 0.03). A higher Ikaros expression in the recipients' PB 3 weeks after engraftment was also associated with a significantly higher risk of moderate/severe chronic GVHD (65% vs. 11%, respectively, P = 0.005). In conclusion, Ikaros expression in the graft and in the recipients' PB after transplantation was associated with a higher risk of moderate/severe chronic GVHD. Ikaros expression should be evaluated in larger prospective trials as a potential biomarker for chronic GVHD.
Subject(s)
Bronchiolitis Obliterans Syndrome , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Ikaros Transcription Factor , Leukemia, Myeloid, Acute , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Chronic Disease , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Leukemia, Myeloid, Acute/etiology , Prospective Studies , Recurrence , Ikaros Transcription Factor/genetics , Ikaros Transcription Factor/metabolismABSTRACT
Patients with refractory severe aplastic anemia (SAA) who lack a matched sibling or unrelated donor need new therapeutic approaches. Hematopoietic SCT (HSCT) using mismatched or haploidentical related donors has been used in the past, but was associated with a significant risk of GVHD and mortality. Recently, the use of post-transplant cyclophosphamide (Cy) has been shown to be an effective strategy to prevent GVHD in recipients of haploidentical HSCT, but the majority of reports have focused on patients with hematology malignancies. We describe the outcome of 16 patients who underwent haploidentical transplantation using a reduced-intensity conditioning regimen with post-transplant Cy. Stem cell sources were BM (N=13) or PBSCs (N=3). The rate of neutrophil engraftment was 94% and of platelet engraftment was 75%. Two patients had secondary graft failure and were successfully salvaged with another transplant. Three patients developed acute GVHD being grades 2-4 in two. Five patients have died and the 1-year OS was 67.1% (95% confidence interval: 36.5-86.4%). In our small series, the use of a reduced-intensity conditioning with post-transplant Cy in haploidentical BMT was associated with high rates of engraftment and low risk of GVHD in patients with relapsed/refractory SAA.
Subject(s)
Anemia, Aplastic/therapy , Bone Marrow Transplantation , Cyclophosphamide/administration & dosage , Graft vs Host Disease/prevention & control , Immunosuppressive Agents/administration & dosage , Transplantation Conditioning , Acute Disease , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
Oxaliplatin is a third generation platinum compound that inhibits DNA synthesis, mainly through intrastrandal cross-links in DNA. Most of the experience with the clinical use of this drug is derived from colorectal cancer but it is also used in other tumor types such as ovary, breast, liver and non-Hodgkin's lymphoma. Thrombocytopenia is a frequent toxicity seen during oxaliplatin treatment, occurring at any grade in up to 70% of patients and leading to delays or even discontinuation of the chemotherapy. Although myelossupression is recognized as the main cause of oxaliplatin-related thrombocytopenia, new mechanisms for this side-effect have emerged, including splenic sequestration of platelets related to oxaliplatin-induced liver damage and immune thrombocytopenia. These new pathophysiology pathways have different clinical presentations and evolution and may need specific therapeutic maneuvers. This article attempts to review this topic and provides useful clinical information for the management of oxaliplatin-related thrombocytopenia.
