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OBJECTIVE: To document the results of outpatient hematopoietic stem cell transplantation (HSCT) from the peripheral blood (PB) of sibling donors without anti-thymocyte globulin (ATG) in the conditioning regimen. MATERIAL AND METHODS: Patients from a low-income population with severe AA who received a PB, unmanipulated sibling HLA-identical HSCT between 2000 and 2020 at a single institution were studied. Survival was the primary outcome. RESULTS: Forty-one transplants were performed. Time between diagnosis and transplant was five months (1-104). Median age was 37 (range, 4-61) years; 25 (61 %) recipients were males and 32 (78 %) had treatment failure, 9 (22 %) have not received treatment. ATG was administered in 5 (12.2 %) cases; the graft source was PB in 38 (92.7 %) transplants. Twenty-six (63.4 %) transplants were carried out in the outpatient setting. Infections developed in 14 (34.1 %) patients. Primary graft failure (GF) occurred in 3 (7.3 %) patients. The 15-year OS was 81 %, EFS was 77.4 %. Patients with high pre-HSCT transfusion burden had lower OS (p = 0.035) and EFS (p = 0.026). Previous treatment failure and age were not associated with lower OS (p = 0.115, p = 0.069) or EFS (p = 0.088, p = 0.5, respectively). CONCLUSIONS: HLA-identical T-cell replete outpatient HSCT from the PB of sibling donors for AA patients using ATG-free conditioning offers excellent long-term survival.

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Haploidentical hematopoietic can be conducted on an outpatient basis but the two main reasons to accept into the hospital a patient in this setting are complications of the hematological toxicity and/or the cytokine-release syndrome. With the aim of reducing the post-transplant cyclophosphamide-dependent toxicity without compromising its effectivity, attempts to reduce the dose of post-transplant cyclophosphamide have been made: Decreases from the conventional total dose of post-transplant cyclophosphamide (100 mg/Kg) have been explored worldwide, showing that decreasing the total dose to even 50 mg/Kg significantly decreases the toxicity of the procedure without compromising its efficacy, safety and results. We present here the salient data of the attempts to diminish the doses of post-transplant cyclophosphamide which have been done and published worldwide, information that suggests that the conventional doses of post-transplant cyclophosphamide can be significantly reduced thus decreasing the toxicity, without compromising the effectiveness of the procedure, mainly the development of graft versus host disease.

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BACKGROUND: HLA compatibility predicts allogeneic hematopoietic cell transplant (allo-HCT) and graft-versus-host disease (GvHD) outcomes. There is insufficient information regarding GvHD outcomes for outpatient HLA-identical and haploidentical-HCT employing reduced-intensity conditioning (RIC). RESEARCH DESIGN AND METHODS: We compare GvHD outcomes between donor types and report risk factors associated with GvHD. Stem cell source was T-cell replete peripheral blood. GvHD prophylaxis was post-transplant cyclophosphamide (PT-CY), mycophenolic acid, and calcineurin inhibitors for haploidentical (n = 107) and oral cyclosporine (CsA) plus methotrexate i.v. for HLA-identical (n = 89) recipients. RESULTS: One hundred and ninety-six HCT transplant patients were included. aGvHD and cGvHD frequency were similar between HCT types. aGvHD severity was comparable, but severe cGvHD was less frequent in the haploidentical group (p = .011). One-hundred-day cumulative incidence (CI) of aGvHD for haploidentical and HLA-identical was 31% and 33% (p = .84); 2-year CI of cGvHD was 32% and 38% (p = .6), respectively. Haploidentical recipients had less steroid-refractory cGvHD (p = .043). Patients with cGvHD had less 2-year relapse (p = .003); both aGvHD and cGvHD conferred higher OS (p = .010 and p = .001), respectively. Male sex was protective for steroid-refractory cGvHD (p = .028). CONCLUSIONS: Acute and chronic GvHD rates were comparable between HLA-identical and haploidentical transplant groups. cGvHD severity was lower in the haploidentical group.

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BACKGROUND: While second-generation tyrosine kinase inhibitors (TKI) revolutionized treatment for patients with chronic myeloid leukemia (CML) who developed a suboptimal response to imatinib, many patients in developing countries are fixed to the latter due to socioeconomic barriers. Despite this scenario, scarce information is available to evaluate the clinical prognosis of these patients. METHODS: We conducted a retrospective cohort analysis to compare the overall mortality of patients with CML who developed a suboptimal response to a standard dose of imatinib and were treated with either high-dose imatinib or a second-generation TKI. We created a marginal structural model with inverse probability weighting and stabilized weights. Our primary outcome was overall survival (OS) at 150 months. Our secondary outcomes were disease-free survival (DFS) at 150 months and adverse events. RESULTS: The cohort included 148 patients, of which 32 received high-dose imatinib and 116 a second-generation TKI. No difference was found in the 150-month overall survival risk (RR: 95% CI 0.91, 0.55-1.95, P-value = .77; RD: -0.04, -0.3 to 0.21, P-value = .78) and disease-free survival (RR: 1.02, 95% CI 0.53-2.71, P-value = .96; RD: 0.01, -0.26 to 0.22, P-value = .96). There was also no difference in the incidence of adverse events in either group. CONCLUSION: Ideally, patients who develop a suboptimal response to imatinib should be switched to a second-generation TKI. If impossible, however, our findings suggest that patients treated with high-dose imatinib have a similar overall survival and disease-free survival prognosis to patients receiving a second-generation TKI.

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BACKGROUND: Despite the improvements in supportive care for allogeneic-hematopoietic cell transplantation (allo-HCT) recipients, infectious complications and infection-related mortality (IRM) continue to be a major issue for transplantation centers. METHODS: We herein report the infectious complications and IRM of 107 and 89 patients that underwent haploidentical (haplo-HCT) or HLA-identical HCT at a tertiary referral center during 2013-2020. Patients in the haplo-HCT group received post-transplant cyclophosphamide (PT-Cy), and all received reduced-intensity conditioning regimens. RESULTS: More haplo-HCT recipients presented severe infections in the pre-engraftment period (22.4% vs. 6.7%, p = 0.003). Viral (14.9% vs. 4.5%, p = 0.016) and fungal (12.1% vs. 1.1%, p = 0.003) etiologies were more common in this period in this group. The 100-day and 2-year cumulative incidence of IRM was 15% and 21% for the haplo-HCT and 5.6% and 17% for the HLA-identical group; no significant differences were observed between the groups. Fungal pathogens mainly contributed to IRM (33.3%). Infections were the most common cause of mortality (40/81, 49.4%). There were significant differences in donor/recipient CMV serostatus between transplant groups (0.002). CONCLUSIONS: No differences in IRM were observed based on allo-HCT type, with more haplo-HCT patients suffering from severe infections in the pre-engraftment period. Studies to assess future prevention, diagnostic, and treatment strategies to reduce IRM are warranted.

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Abstract Introduction Hemorrhagic cystitis (HC) is a common complication of haploidentical hematopoietic stem cell transplantation (haplo-HSCT), characterized by irritative symptoms of the urinary tract and a higher morbidity and mortality rate. The worldwide incidence is reported between 10% and 70%. The use of alkylating agents and BK viral infection are the most frequent etiologies. The aim of this study was to report the HC incidence in an outpatient haplo-HCST program with a reduced intensity-conditioning (RIC) regimen, cataloguing risk factors, complications and final outcomes. Methods The medical database of patients who received a haplo-HSCT between January 2012 and November 2017 was retrospectively analyzed. Demographic variables, general characteristics and HC incidence were included. Results One hundred and eleven patients were included, 30 (27%) of whom developed HC, most of them (70%) being grade II, with a 30-day (7-149) median time of post-transplant HC onset. The BK virus was detected in 71% of the urine samples analyzed. All HC patients responded to treatment, except two (6.6%), who died due to HC complications. Conclusions There was no difference in the HC incidence or severity, compared to that reported when performing haplo-HSCT in hospitalized patients, although the donor-recipient sex mismatch did relate to a higher HC incidence.

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Hematopoietic stem-cell transplantation (HSCT) is usually performed in well-equipped units inside a hospital. The cost of this in-hospital transplant is usually very high; therefore, this procedure is more difficult to perform in low- and middle-income countries. Autologous outpatient HSCT is now a common procedure; however, outpatient allogeneic transplants are more complicated. Only a few centers in the world have incorporated outpatient HSCT. This transplant requires special adaptation, like a day hospital, careful selection of patients, oral medications, and the patient must live relatively close to the hospital. The results until now suggest that this outpatient transplant is factible and similar to inpatient HSCT. The objective was to review and describe the different methods and results following an outpatient allogeneic-HSCT strategy.

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INTRODUCTION: Hemorrhagic cystitis (HC) is a common complication of haploidentical hematopoietic stem cell transplantation (haplo-HSCT), characterized by irritative symptoms of the urinary tract and a higher morbidity and mortality rate. The worldwide incidence is reported between 10% and 70%. The use of alkylating agents and BK viral infection are the most frequent etiologies. The aim of this study was to report the HC incidence in an outpatient haplo-HCST program with a reduced intensity-conditioning (RIC) regimen, cataloguing risk factors, complications and final outcomes. METHODS: The medical database of patients who received a haplo-HSCT between January 2012 and November 2017 was retrospectively analyzed. Demographic variables, general characteristics and HC incidence were included. RESULTS: One hundred and eleven patients were included, 30 (27%) of whom developed HC, most of them (70%) being grade II, with a 30-day (7-149) median time of post-transplant HC onset. The BK virus was detected in 71% of the urine samples analyzed. All HC patients responded to treatment, except two (6.6%), who died due to HC complications. CONCLUSIONS: There was no difference in the HC incidence or severity, compared to that reported when performing haplo-HSCT in hospitalized patients, although the donor-recipient sex mismatch did relate to a higher HC incidence.

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INTRODUCTION: Historically, the measurement of serum procalcitonin (PCT) levels in patients with leukopenia has been rejected without sufficient prospective evidence to justify this argument. On the other hand, the accumulated use of broad spectrum antibiotics in these patients and their consequences make the use of PCT attractive in an effort to reduce its use. PATIENTS AND METHODS: We conducted a prospective study between 2016 and 2018, recruiting newly diagnosed FN patients, evaluating them with PCT levels during the first 24 h. After this we evaluate them with overall survival throughout the follow-up. RESULTS: A total of 81 episodes of FN in 72 patients were included. We report a mortality of 27.2% in our cohort. The mean serum PCT in these patients was 4.01 ng/mL compared to 0.42 ng/mL in the survivors group (p < 0.01). Using ROC curves, we determined a cut-off point to predict septic shock/death at 0.46 ng/mL. Patients with a procalcitonin >0.46 ng/mL had an increased risk of death, with a HR of 4.43, (p = 0.048). CONCLUSION: In conclusion, in our trial a single PCT on admission at a cut-off value of 0.46 ng/mL was able to predict the occurrence of septic shock and death in FN patients.

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BACKGROUND: Hematopoietic stem cell transplantation (HSCT) feasibility has increased in the last decades because of haplo-HSCT, changes in chemotherapy schedules, and the possibility of an outpatient-based HSCT. The main barriers remain in low-middle income countries. There is a lack of information regarding haplo-HSCT with a myeloablative (MAC) regimen on an outpatient basis. OBJECTIVES: Our primary objective was to determine if outpatient haplo-HSCT was feasible. STUDY DESIGN: Single center, retrospective cohort, n=60 adult patients undergoing Haplo-HSCT. Descriptive statistical analysis, univariate and multivariate comparison. PATIENTS AND METHOD: We analyzed 60 adult patients transplanted with an intended haplo-HSCT on an outpatient basis from 2015 to 2019 in our unit. A multivariate analysis was performed on risk factors for hospitalization. RESULTS: Median age was 27 years (15-64). All patients underwent conditioning as outpatients, and none required hospitalization before day 0. Thirteen patients (21.6%) were followed completely in the outpatient clinic and 47 (78.3%) required hospitalization in a median of 3 days after infusion (range, 1-14). The median length of stay (LOS) was 8 days (IQR, 3-17). Fever secondary to cytokine release syndrome (CRS) was the most common reason for hospitalization occurring in 43/47 (91.5%), 4 were related to infection and 36 were related to CRS. In the univariate analysis, CRS, slower engraftment, and female sex were associated with the need for hospitalization. In the multivariate analysis, only CRS remained significant (OR 9.14 [95%CI, 1.58-56.46]). The 2-year overall survival (OS) was 41.7% for ambulatory transplant vs. 38% for those requiring hospitalization (P = 0.12). The 2-year event-free survival (EFS) was 33% for outpatient patients and 16.7% for those hospitalized (log-rank, P = 0.062). CONCLUSIONS: We demonstrated the feasibility and safety of carrying out an outpatient haplo-HSCT, potentially resulting in cost savings and perhaps a higher quality of life.

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Autologous stem cell transplantation (ASCT) is commonly an in-patient procedure. However, outpatient ASCT grows as a cost-effective and feasible option for patients with lymphoma and reports assessing it after reduced-intensity conditioning (RIC) are sparse. We report the outcome of 102 patients with lymphoma who underwent ASCT on a full outpatient basis in a single-center transplant program between 2010 and 2020. Forty-two percent of the cohort required transfusion support, 36.3% experienced a neutropenic fever episode, 25.5% mucositis, and 9.8% developed severe infection. At a median time of 5 days (range 1-28), only 22.5% of the cohort required admission within the first 100 days after the autograft, median length of hospital stay was 0 days (range 0-14) and neutropenic fever was the most common reason for hospitalization. Non-relapse mortality at 1 year was 5%. ASCT in a completely outpatient setting is feasible, safe, and highly effective to treat lymphoma patients.

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PURPOSE: To evaluate the safety and efficacy of ocular cyclosporine in the prevention of the development of ocular graft versus host disease (oGVHD) in patients undergoing allogeneic hematopoietic stem cell transplantation (AHSCT) in comparison with historic data. DESIGN: We developed a longitudinal, observational, prospective nonrandomized study. We evaluated the feasibility of prophylactic use of topical cyclosporine A (CsA) to prevent or decrease the incidence of oGVHD and compared this with historic data. METHODS: Patients undergoing AHSCT were treated with prophylactic topical CsA for 12 months after engraftment, followed by serial ophthalmic evaluations, including the Schirmer test. RESULTS: Twenty patients were included. No serious adverse effects were reported. Poor adherence was documented in 15% of patients. In spite of observing extra-ocular GVHD (acute and chronic GVHD incidence of 50 and 45%, respectively), only 1 in 20 patients developed oGVHD over the 20-month follow-up for the entire cohort. No statistically significant difference was observed in the incidence of oGVHD when compared to a historical cohort. CONCLUSIONS: Topical CsA as a prophylactic measure for oGVHD, administered over a period of 1 year after grafting, is safe and feasible and may decrease the incidence of ophthalmic manifestations of GVHD. These findings must be confirmed in a randomized trial.

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BACKGROUND: Autologous stem cell transplantation (ASCT) is an effective treatment for patients with relapsing myeloma or lymphoma, diseases associated with unsuccessful peripheral blood stem cell (PBSC) collection. Plerixafor is a potent mobilizing agent, allowing more CD34+ cells to be obtained; however, the main obstacle for its use is its high cost. Our aim was to demonstrate that of the use of reduced doses of plerixafor (RD-plerixafor) can be sufficient to collect at least 2 × 106 /Kg CD34+ PBSC in patients with multiple myeloma (MM) or lymphoma undergoing ASCT. STUDY DESIGN AND METHODS: Twenty patients were mobilized with filgrastim (10 µg/kg/4 days) plus a single dose of plerixafor 0.12 mg/kg in Day 4. Apheresis collection was performed on Day 5. One vial of plerixafor was used for two patients. Clinicaltrials.gov NCT03244930. RESULTS: Cell mobilization and collection was successful in 85% of patients (≥2 × 106 CD34+ cells per kilogram). The median collected CD34+ cell count was 4.62 × 106 /kg (range, 1.27-24.5). A 4.1-fold-increase in the median CD34+ PBSC pre-count was observed (from 10.4/µl to 42.4/µl) after RD-plerixafor administration. Seven patients had mild to moderate adverse events. CONCLUSION: RD-plerixafor is an effective, safe, and affordable strategy to ensure adequate PBSC mobilization in patients with MM or lymphoma who undergo ASCT.

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Efficacy of an ambulatory hematopoietic stem cell transplant (HSCT) program with a reduced intensity conditioning regimen (RIC) in malignant hematological diseases was assessed. We analyzed 217 patients who underwent HSCT from August 2013 to July 2017. There were 78 (35.9%) HLA-identical, 56 (25.8%) haploidentical, and 83 (38.2%) autologous transplants. Two-year transplant-related mortality (TRM) for HLA-identical, haploidentical, and auto grafts were 20%, 25%, and 2.5%; relapse/progression was 44%, 60%, and 55%; overall survival (OS) was 61%, 44.8%, and 78.0%; and disease-free survival (DFS) was 36.8%, 26.5%, and 43.5%, respectively. Factors associated with a high risk of TRM were male sex (HR = 2.62, P = 0.031), fever and neutropenia (HR = 3.30, P = 0.023), and cell dose < 5 × 106 CD34 +/kg (HR = 4.24, P = 0.001); cGVHD was a protective factor for TRM (HR = 0.29, P = 0.022). Transfusion was associated with increased risk of relapse/progression in univariate and multivariate analysis (HR = 3.10, P = 0.001 and HR = 3.30, P = 0.004); cGVHD was a protective factor (HR = 0.18, P = 0.001 and HR = 0.17, P = 0.002). In a multivariate analysis for allo-HSCT, infections were associated with high risk of mortality (HR = 3.90, P = 0.016) and transfusion with reduced DFS (HR = 2.76, P = 0.029); for haplo-HSCT, CD34 + < 5 × 106/kg was a risk factor for mortality and lower DFS (HR = 5.41, P = 0.001 and HR = 3.93, P = 0.001). Outcomes of our RIC-based outpatient transplant program are comparable to excellence centers in high-income countries.

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