Splenectomy before allogeneic stem cell transplantation (ASCT) for patients with myelofibrosis (MF) remains a matter of debate, and conflicting results have been reported to date. The procedure seems ...to fasten post-transplant hematological recovery, but it does not have an impact on survival. The role of pre-transplant splenic irradiation (SI) is much more difficult to evaluate. Forty-four patients (25 males and 19 females) with MF at median age of 49 years at diagnosis (range 14–67) underwent ASCT. The post-transplant outcome was compared between irradiated and non-irradiated patients. Eleven patients received irradiation before transplantation. Median dose of radiation was 1000 cGy (range 600–2400). There was no difference in median time to engraftment between patients with and without previous radiotherapy. Acute and chronic graft versus host disease (GVHD) occurred in 47% and 36% of patients, respectively. There was no difference in GVHD incidence between groups. Eight patients relapsed/progressed in irradiated group versus 17 in non-irradiated (70% vs. 51%;
p
= 0.3). Transformation to acute myeloid leukemia was observed in 3 patients: 2 in irradiated and 1 in non-irradiated group. In total, 22 patients died with no statistical difference in death rate between irradiated and non-irradiated subjects. The probability of overall survival after transplant for the entire cohort at 2 years was 54% (72% for irradiated and 48% for non-irradiated patients;
p
= 0.25). Splenic irradiation prior to ASCT for myelofibrosis has not beneficial effect on post-transplant outcome.
The administration of azacitidine (AZA) was found to be more effective than conventional care regimen (CCR) in patients with higher-risk myelodysplastic syndromes (MDS), chronic myelomonocytic ...leukemia (CMML) and acute myeloid leukemia (AML) with lower blast count. We designed a study to determine efficacy and safety of AZA therapy in “real life” patients with MDS, CMML and AML. The study included 83 patients (65% male) with a median age at diagnosis of 68 years. 43 patients were diagnosed with higher-risk MDS, 30 had AML and 10-CMML. Median AZA dose was comparable between treated groups. AZA dose reduction was required for 44% of MDS, 17% of AML and 25% of CMML patients. Complete remission (CR) was achieved in 14% of MDS, 7% of AML and 10% of CMML patients. Overall response rate was following: 27% for MDS, 20% for AML and 20% for CMML. Estimated OS at 12 months was 75% for MDS, 60% for AML and 75% for CMML. Median follow-up for MDS/AML/CMML from AZA initiation to last follow-up was 9.0, 9.4 and 9.4 months, respectively. The most common toxicity of AZA therapy was myelosuppression and infections. AZA treatment was effective in a limited number of patients with acceptable safety profile.
New therapies for refractory angina are needed.
Assessment of transendocardial delivery of bone marrow CD133
cells in patients with refractory angina.
Randomized, double-blinded, placebo-controlled ...trial enrolled 31 patients with recurrent Canadian Cardiovascular Society II-IV angina, despite optimal medical therapy, ≥1 myocardial segment with inducible ischemia in Tc-99m SPECT who underwent bone marrow biopsy and were allocated to cells (n=16) or placebo (n=15). Primary end point was absolute change in myocardial ischemia by SPECT. Secondary end points were left ventricular function and volumes by magnetic resonance imaging and angina severity. After 4 months, there were no significant differences in extent of inducible ischemia between groups (summed difference score mean ±SD: 2.60 2.6 versus 3.63 3.6,
=0.52; total perfusion deficit: 3.60 3.6 versus 5.01 4.3,
=0.32; absolute changes of summed difference score: -1.38 5.2 versus -0.73 1.9,
=0.65; and total perfusion deficit: -1.33 3.3 versus -2.19 6.6,
=0.65). There was a significant reduction of left ventricular volumes (end-systolic volume: -4.3 11.3 versus 7.4 11.8,
=0.02; end-diastolic volume: -9.1 14.9 versus 7.4 15.8,
=0.02) and no significant change of left ventricular ejection fraction in the cell group. There was no difference in number of patients showing improvement of ≥1 Canadian Cardiovascular Society class after 1 (41.7% versus 58.3%;
=0.68), 4 (50% versus 33.3%;
=0.63), 6 (70% versus 50.0%;
=0.42), and 12 months (55.6% versus 81.8%;
=0.33) and use of nitrates after 12 months.
Transendocardial CD133
cell therapy was safe. Study was underpowered to conclusively validate the efficacy, but it did not show a significant reduction of myocardial ischemia and angina versus placebo.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01660581.
Objective: Oral mucositis occurs in 75% to 100% of allogeneic HSCT recipients can cause pain, facilitate
infections, delay discharge, and threaten life. The aim of the study was to evaluate ...prophylaxis
with the remineralizing mouthwash solution of supersaturated calcium phosphate rinse
(SCPR) with Fomukal on measures of severity of mucositis and consequent interventions and
complications, in comparison to Caphosol, already evaluated post-transplant.
Materials/Methods: In this prospective, randomized, non-inferiority trial, 46 patients undergoing allogeneic HSCT
were equally randomized to Fomukal or Caphosol, each administered four times daily from
initiation of conditioning until the granulocyte count ≥0.2 G/L. Hematologist measured the
daily severity of mucositis according to a WHO scale and patients self-assessed its symptoms.
Need for analgesics, anti-infectious drugs, total parenteral nutrition (TPN) and incidence of
complications were also assessed.
Results: Fomukal vs. Caphosol groups had the same all following indicators: median measures of WHO
oral mucositis reduction (0 vs. 2; P = NS), length of disease course (0 vs. 6 days; P = NS), peak and
mean mouth (1 vs. 2; P = NS and 0.06 vs. 1; P = NS) and throat pain (1 vs. 1; P = NS and 0.22 vs.
0.31; P = NS), and peak and mean swallowing problems (1 vs. 1; P = NS and 0.19 vs. 0.25; P = NS).
Analgesics need (7 vs. 10 patients; 0 vs. 0 days; P = NS) and the need for antifungals (1 vs. 2 drugs;
P = NS) were not different, while the need for antibiotics and antivirals (3.5 vs. 5 drugs; P = 0.011
and 1 vs. 2 drugs; P = 0.023) were lower in the Fomukal group. Measures of complications: infections
(7 vs. 12 patients, P = NS) and a GVHD (13 vs. 14 patients, P = NS, grade 1 vs. 1, P = NS) did not differ.
Discussion: Both SCPR mouth rinses, Fomukal and Caphosol, were associated with similar effectiveness in
reducing severity of oral mucositis.
Pyoderma gangrenosum (PG) is an uncommon, serious, ulcerating skin disease of uncertain etiology. It manifests as a noninfectious, progressive necrosis of the skin characterized by sterile ...neutrophilic infiltrates. It seems to be a disorder of the immune system. PG is associated with certain underlying conditions in at least 50% of cases. Therefore, it is important to look carefully for comorbidities in every patient with PG and treat them adequately to improve the prognosis. Here, we demonstrate a 35-year-old man diagnosed with multifocal PG and hemophagocytic lymphohistiocytosis (HLH) with fatal outcome, despite combined, long-term, intensive dermatological and hematological treatment with high doses of steroids, cyclosporin, intravenous immunoglobulins (IVIG), HLH-2004 protocol with intravenously administered etoposide, and anakinra. This case is presented owing to the extremely rare coexistence of PG and HLH and the related diagnostic and therapeutic difficulties. It is also worth underlying that the diagnosis of HLH should perhaps be considered in the presence of a high percentage of double-negative T lymphocytes (DNTs) in flow cytometry, after excluding the diagnosis of lymphoma and leukemia. In this article we have also performed and present the critical literature review of local and systemic options in the management of PG lesions based on a detailed search of the PubMed database.
T cell activation plays a crucial role in the development of acute graft versus host disease (aGvHD). Cytotoxic T cell antigen-4 (CTLA-4) is a co-inhibitory molecule that negatively regulates T cell ...activation, differentiation, and proliferation. Single-nucleotide polymorphisms (SNPs) in
CTLA-4
gene may affect its function. Inconsistent observations have been reported regarding the associations of
CTLA-4
SNPs with complications after hematopoietic stem cell transplantation (HSCT). Moreover, the majority of the observations were focused on the donors’ SNPs. Recently, a few studies have shown that recipients’ genetic variations in the
CTLA-4
gene might influence HSCT results. The aim of our study was to determine the influence of the
CTLA-4
gene polymorphisms of the donors and the recipients on the outcome of HSCT. Altogether, 312 donor-recipient pairs were genotyped for the
CTLA-4
c.49A>G (rs231775) and CT60G>A (rs3087243) SNPs using the TaqMan®SNP Genotyping Assays. In this study, it was shown that the recipients’ CT60G>AGG genotype, the myeloablative conditioning regimen, and HSCT from an unrelated donor were independent aGvHD risk factors (odds ratio (OR) 2.63, 95 % confidence intervals (95 % CI) 1.45–4.59,
p
= 0.001; OR 2.68, 95 % CI 1.65–4.07,
p
= 0.00003; and OR 1.87, 95 % CI 1.02–3.24,
p
= 0.04, respectively). Moreover, haplotype analysis revealed that possessing allele A in both of the SNPs decreased the risk of aGvHD approximately 1.5-fold (RR 0.69,
p
= 0.008). Our data suggest that the CT60G>AGG genotype in the recipient has an impact on aGvHD development, especially in patients receiving transplants from unrelated donors together with the myeloablative conditioning regimen.
To provide real-world data on the impact of autologous hematopoietic stem cell transplantation (AHSCT) on treatment costs of patients with multiple sclerosis (MS) in Poland.
Medical data of 105 ...patients who underwent AHSCT in the years 2011 to 2016 were obtained from the National Health Fund (NHF) database. Treatment costs were calculated from the public payer’s perspective per patient-year for the total available period as well as 12 months before and after AHSCT. The statistical analysis was performed using MATLAB 2016b.
Mean treatment-related costs covered by the NHF per patient-year before and after the transplantation were €4314.9 and €1188.8 , respectively. The average cost of disease-modifying drugs per patient was reduced from €2497.9/year before to €65.3/year after AHSCT.
Although the initial cost of AHSCT is high, the costs involving AHSCT and post-AHSCT treatment could, according to our analysis, pay off in 3.9 years, when compared to the costs of disease-modifying drug therapy in aggressive MS. The study provides evidence that the AHSCT can lead to significant savings in treatment costs of aggressive MS from the public payer’s perspective.
•The autologous hematopoietic stem cell transplantation (AHSCT) has been acknowledged as novel standard treatment in aggressive multiple sclerosis (MS); however, little is known of potential real-life impact on treatment costs.•A real-life nationwide analysis of medical costs before and after AHSCT of patients with MS who underwent this treatment is provided.•Massive reduction of treatment cost following AHSCT is observed in patients with MS.
Autologous hematopoietic stem cell transplantation (AHSCT) is thought to be effective therapeutic approach in patients with poor prognosis systemic sclerosis; however, the toxicity remains a ...challenge. Between years 2003 and 2016, we enrolled 18 patients with systemic sclerosis at median age at transplant of 52 years (range 24–68). The median duration of disease before AHSCT was 14 months (range 2–85). Peripheral blood stem cells were mobilized with cyclophosphamide (CY) and granulocyte colony-stimulating factor. Conditioning regimen included CY (200 mg/kg) and alemtuzumab (median dose, 60 mg)
n
= 11, melphalan (MEL; 140 mg/m2) and alemtuzumab
n
= 2, CY and rabbit anti-thymocyte globulin (rATG; 7.5 mg/kg)
n
= 4, and CY alone (
n
= 1). Four deaths occurred early after transplant. There were three males and one female at median age at death of 51 years (range 24–68). The AHSCT-related deaths have been observed on days + 1, + 4, + 9, and + 15 after procedure. The causes of death included bilateral pneumonia followed by multi-organ failure in three patients and myocardial infarction in one. Three patients expired late during post-transplant follow-up, after 5, 21, and 42 months. The causes of death were disease progression in two patients and sudden heart attack in one. Eleven patients are alive after median follow-up after AHSCT of 42.0 months (range 0–95). Before proceeding to AHSCT in systemic sclerosis, there is a strong need to optimize patient selection to reduce toxicity. The administration of alemtuzumab should be avoided due to high risk of life-threatening infectious complications.
An alternative reduced-toxicity conditioning regimen for allogeneic transplantation, based on treosulfan and fludarabine, has recently been identified. The rationale for this study was to investigate ...the efficacy and safety of this regimen prospectively in patients with a primary myelodysplastic syndrome.
A total of 45 patients with primary myelodysplastic syndromes were conditioned with 3×14 g/m(2) treosulfan and 5×30 mg/m(2) fludarabine followed by allogeneic hematopoietic stem cell transplantation. Subtypes of myelodysplastic syndromes were refractory anemia with excess blasts-2 (44%), refractory cytopenia with multilineage dysplasia (27%), refractory anemia (9%), refractory anemia with ringed sideroblasts (4%), refractory cytopenia with multilineage dysplasia and ringed sideroblasts (4%), refractory anemia with excess blasts-1 (2%), and myelodysplastic syndrome with isolated del (5q) (2%). The myelodysplastic syndrome was unclassified in 7% of the patients. Forty-seven percent of the patients had a favorable karyotype, 29% an unfavorable one, and 18% an intermediate karyotype. Patients were evaluated for engraftment, adverse events, graft-versus-host disease, non-relapse mortality, relapse incidence, overall survival and disease-free survival.
All but one patient showed primary engraftment of neutrophils after a median of 17 days. Non-hematologic adverse events of grade III-IV in severity included mainly infections and gastrointestinal symptoms (80% and 22% of the patients, respectively). Acute graft-versus-host disease grade II-IV developed in 24%, and extensive chronic graft-versus-host disease in 28% of the patients. After a median follow-up of 780 days, the 2-year overall and disease-free survival estimates were 71% and 67%, respectively. The 2-year cumulative incidences of non-relapse mortality and relapse were 17% and 16%, respectively.
Our safety and efficacy data suggest that treosulfan-based conditioning therapy is a promising treatment option for patients with myelodysplastic syndromes. clinicaltrials.gov identifier: NCT01062490.
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