Introduction: The use of a Myeloablative (MA) regimen followed bypost-transplantation high dose Cyclophosphamide (PT-CY) has been adopted to overcome the increased relapse risk following nonmyeloablative conditioning regimen and unmanipulated Haploidentical Bone Marrow Transplantation, in patients with high-risk hematological malignancies, with acceptable TRM and risk of GVHD. We added ATG to our Myeloablative regimen with PT-CY after noticing significant incidence of grade II-IV aGVHD with the first few cases. Here we compare the outcomes of the 12 patients who received ATG to the outcomes of the first 11 patients who were transplanted without ATG. Patients and Methods: our haploidentical program was started in 2013 as a phase I/II prospective clinical trial. After reviewing the first 11 cases enrolled on the trial (MA regimen with PT-CY, without ATG), we noticed significant incidence of high grade aGVHD (54.55%). We amended our protocol in early 2015. Rabbit ATG was added at a dose of 3 mg/kg (1.5 mg/kg day -3 and day -2) to our conditioning regimen [thiotepa (5mg/kg/day on day -8 and -7), busulfan (3.2mg/kg/day IV day-6, -5 and -4), fludarabine (50mg/m2/day on day -6, -5 and -4 )] or [TBI 1000 cGy (200cGy twice a day on days -10, -9 and one dose on day -8), fludarabine (30mg/m2/day on Days -7, -6, -5 and -4)]. Graft-versus-host disease (GVHD) prophylaxis consisted of PT-CY (50mg/kg/day) on days +3 and +5, cyclosporine (starting day +4), and mycophenolate mofetil (starting day +1). Table 1 summarizes the disease-type and disease-status at transplant. Patient characteristics were comparable at baseline between the 2 groups. Results (Table 2): We enrolled patients with high risk hematologic malignancies in need for SCT but have no matched donor (MSD, MUD). Despite the small sample size, our results showed a statistically significant difference in the rate of acute GVHD between the 2 groups (p= 0.0161) in favor of the ATG group, chronic GVHD was more frequent in the non-ATG group however the difference did not reach statistical significance probably due to the small sample size. There was no statistically-significant difference in the risk of relapse, CMV reactivation or Hemorrhagic cystitis between the 2 groups. However, there was a trend of higher relapse rate (33.3% vs 18.18%), a higher rate of Hemorrhagic cystitis (50% vs 18.18%) and a higher rate of CMV reactivation (100% vs 81.82%) in the ATG group. The cumulative incidence of TRM at day 100 was in favor of the ATG group (figure 1), with a trend toward a better DFS in these patients 6 months post-transplant (figure 2). To be noted the follow up period was shorter for the ATG group because ATG was added later on. Figure 3 shows the survival for ATG vs non ATG group. Conclusion: The use of ATG with myeloablative Haplo conditioning can significantly reduce the risk of acute GVHD and early TRM. We have seen more relapses, higher rate of CMV reactivation, and hemorrhagic cystitis with the addition of ATG but these did not reach statistical significance probably due to the small sample size. A lower dose of ATG might be the way to go to strike a careful balance and improve the outcomes of myeloablative haploidentical transplant. Disclosures No relevant conflicts of interest to declare.
Introduction Allogeneic hematopoietic stem cell transplant (allo-SCT) is the only curative treatment modality for patients with CMML. Here we retrospectively reviewed the data for patients with CMML who received an all-SCT at our institution to identify factors associated with improved survival and determine whether treatment with hypomethylating agents (HMA) before transplant improves survival for these patients. Methods All 83 patients 18 years of age or older with a diagnosis of CMML confirmed at The University of Texas MD Anderson Cancer Center who underwent allo-SCT between April 1991 and December 2013 were identified through review of the institutionÕs medical records and included in this analysis. Forty, 7, and 36 patients had CMML-1, CMML-2 and CMML that had progressed to AML (CMML/AML) respectively. The median age was 57 years. CMML specific cytogenetic risk at diagnosis (Such E, hematologica, 2011) was good, intermediate, and high risk in 46, 19, and 18 patients respectively. Seventy-eight patients received induction treatment before transplant, 37 receiving HMA (either 5-azacytidine or decitabine) for at least 3 courses and 41 receiving 1-2 courses of cytotoxic chemotherapy. Among the patients who received induction therapy, 15 patients in HMA group and 9 patients in convention chemotherapy group achieved a complete remission before transplant. Thirty, 47 and 6 patients received transplants from matched related donors (MRD), matched unrelated donors (MUD), and mismatched related or unrelated donors (MMD), respectively. The sources of hematopoietic stem cells were peripheral blood for 48 patients (57.8%) and bone marrow for 35 patients (42.2%). Conditioning regimens varied; most patients received either fludarabine in combination with busulfan or fludarabine combined with melphalan. Sixty-four patients received myeloablative and 19 patients received reduced intensity conditioning regimens. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus and methotrexate. Patient and transplant characteristics did not significantly differ between the patients treated with HMA and the patients treated with conventional chemotherapy or given supportive care alone. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), Treatment related mortality (TRM), relapse incidence through last follow-up and incidences of acute GVHD and chronic GVHD. All of these outcomes were measured from the time of allo-SCT. Results Median follow up duration for 29 survivors was 48 months. Seventy-five patients engrafted (90.4%) with median time to neutrophil and platelet engraftment of 13 and 15 days respectively. Patients treated with a HMA had a significantly lower cumulative incidence (CI) of relapse at 3 years post-transplant (22%) than those treated with other agents (35%; p=0.03), whereas TRM at 1 year post-transplantdid not significantly differ between the groups (27% and 30%, respectively; p=0.84). Acute GVHD all grades and grade 2-4 were seen in 28.2% versus 35.8% (p=0.05) and 12.8% versus 11.3% (p=0.72) in patients who received a HMA compared to those who treated with other agents respectively. CI of chronic GVHD was 35% in patients treated with a HMA versus 19.2% in those treated with other agents (p=0.36) while CI of chronic extensive GVHD was seen in only 26.7% versus 19.2% respectively (p=0.64). The lower relapse rate resulted in a significantly higher 3-year PFS rate in patients treated with a HMA (43%) than in those who received other treatments (27%; p=0.04) (Figure 1). However, therapy with HMA before transplant did not significantly influence the 3-year OS rate (45% in those treated with HMA and 39% in those treated with other agents; p=0.22). The independent prognostic factors for PFS were a blast count of < 5% before transplant (HR 0.36, 95%CI 0.14-0.78), treatment with a HMA (HR 0.44, 95% CI 0.23-0.86), a transplant from an MRD (HR 0.41, 95% CI 0.22-0.94), development of grade 2-4 acute GVHD (HR 2.7, 95% CI 1.27-5.77), and development of chronic GVHD (HR 0.15, 95% CI 0.05-0.45). Conclusion We conclude that treatment with hypomethylating agents before allo-SCT may improve survival in patients with CMML. Figure 1. Progression free survival Figure 1. Progression free survival Disclosures Alousi: Therakos, Inc: Research Funding. Andersson:Otsuka Research and Development, Inc.: Consultancy.
Background. The QuantiFERON ® -TB Gold assay is a new test for latent tuberculosis infection. It is thought to be more reliable and have fewer false positives than the tuberculin skin test (TST). Both tests are dependent on a normal immune system for diagnostic accuracy. However, no comparisons of the two tests have assessed the accuracy in pregnant women. This investigation assessed the consistency of results between the two tests in both pregnant and nonpregnant women. Methods. The study included 152 women presenting for care at the Sedgwick County Health Department. They were divided into two groups of pregnant and non-pregnant women. Both groups were assessed with the Quantiferon assay and the TST. Subjects were adults between the ages of 18 and 45. All had a pregnancy test and a negative HIV test. None had existing morbidities that would influence the test results. Results. Concordant results between the tests were shown in 131 subjects (86.2%). Of the pregnant women, 91.2% had concordant results. Of the non-pregnant women, 76% had concordant results. Significantly more discordant results occurred in non-pregnant women (p<.022). Conclusion. Current guidelines favor using either test in healthy individuals. Although more discordant results occurred in the non-pregnant women, both tests were effective in pregnant women. Thus, TST and Quantiferon are accurate to use in pregnant women. The decision to use either test in pregnant women should be based mainly on the compliance of the patient to return to have the TST read. KJM 2010; 3(2):24-30.
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