Graft-versus-host disease after an outpatient peripheral blood hematopoietic cell transplant using reduced-intensity conditioning: a single-center LATAM experience.

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.

Lactate dehydrogenase as a hematopoietic stem cell mobilization biomarker in autologous transplantation

ABSTRACT Introduction: Pre-apheresis peripheral blood CD34+ cell count (PBCD34+) is the most important predictor of good cell mobilization before hematopoietic stem cell transplantation, albeit flow cytometry is not always immediately available. Identification of surrogate markers can be useful. The CD34+ cells proliferate after mobilization, resulting in elevated lactate dehydrogenase (LDH) activity and correlating with the PBCD34+ count. Objective: To determine the LDH cut-off value at which adequate CD34+ cell mobilization is achieved and its diagnostic yield. Materials and methods: A total of 103 patients who received an autologous stem cell transplantation (ASCT) between January 2015 and January 2020 were included. Demographic and laboratory characteristics were obtained, including complete blood count, pre-apheresis PBCD34+ and LDH levels. Receiver operating characteristic (ROC) curves were performed to identify the optimal serum LDH activity cut-off points for ≥ 2 and ≥ 4 × 106 cells/kg post-mobilization CD34+ count and their diagnostic yield. Results: A post-mobilization serum LDH cut-off value of 462 U/L yielded a sensitivity (Se) = 86.8% (positive predictive value [PPV] = 72.7%), a pre- and post-mobilization serum LDH difference cut-off value of 387 U/L, an Se = 45.7% (PPV = 97%) and an LDH ratio of 2.46, with an Se = 47.1% (PPV = 97%) for an optimal mobilization count (CD34+ ≥ 4 × 106). Conclusion: The LDH measurement represents a fast and affordable way to predict PBCD34+ mobilization in cases where flow cytometry is not immediately available. According to the LDH diagnostic yield, it could be used as a surrogate marker in transplant centers, supporting the CD34+ count, which remains the gold standard.

Anti-Hla Donor-Specific Antibodies Are Associated to Infection and Not to the Engraftment Rate in Outpatient Haploidentical Hematopoietic Cell Transplantation.

Background: Recipients of a related haploidentical stem cell transplant (haplo-SCT) can have preformed antibodies to HLA donor's antigens. Objective: The aim of the study was to evaluate the engraftment rate and major clinical associations of anti-HLA donor-specific antibodies (DSA) at two mean fluorescence intensity (MFI) thresholds in recipients of an outpatient haplo-SCT. Methods: Seventy haplo-HCT recipients were analyzed. A virtual crossmatch was performed using the donor HLA typing and the recipient's anti-HLA DSA test results. Data for anti-HLA-A, -B, -C, and -DR were analyzed. Recipients with DSA ≥ 500 MFI were considered positive, and those with < 500 were considered negative; the same was adopted for MFI ≥ 1000. Results: Post-transplant infection was higher in recipients with DSA ≥ 500 MFI (84.6%, p = 0.041). First-year mortality was higher in DSA-positive patients ≥ 500 MFI, p = 0.004, and DSA ≥ 1000 MFI, p = 0.022, than in DSA-negative recipients. Graft failure in the first 100 days was not associated with DSA ≥ 500 or ≥ 1000 MFI. There was no difference in acute (a-GVHD) or chronic (c-GVHD) graft versus host disease between DSA-positive and negative patients. Conclusions: There was no association of anti-HLA DSA at MFI ≥ 500 and ≥ 1000 with graft failure, however, increased infection and 1st-year mortality were documented in related haplo-HCT at the MFI cutoffs studied.

Anti-Hla Donor-Specific Antibodies Are Associated to Infection and Not to the Engraftment Rate in Outpatient Haploidentical Hematopoietic Cell Transplantation

ABSTRACT Background: Recipients of a related haploidentical stem cell transplant (haplo-SCT) can have preformed antibodies to HLA donor's antigens. Objective: The aim of the study was to evaluate the engraftment rate and major clinical associations of anti-HLA donor-specific antibodies (DSA) at two mean fluorescence intensity (MFI) thresholds in recipients of an outpatient haplo-SCT. Methods: Seventy haplo-HCT recipients were analyzed. A virtual crossmatch was performed using the donor HLA typing and the recipient's anti-HLA DSA test results. Data for anti-HLA-A, -B, -C, and -DR were analyzed. Recipients with DSA ≥ 500 MFI were considered positive, and those with < 500 were considered negative; the same was adopted for MFI ≥ 1000. Results: Post-transplant infection was higher in recipients with DSA ≥ 500 MFI (84.6%, p = 0.041). First-year mortality was higher in DSA-positive patients ≥ 500 MFI, p = 0.004, and DSA ≥ 1000 MFI, p = 0.022, than in DSA-negative recipients. Graft failure in the first 100 days was not associated with DSA ≥ 500 or ≥ 1000 MFI. There was no difference in acute (a-GVHD) or chronic (c-GVHD) graft versus host disease between DSA-positive and negative patients. Conclusions: There was no association of anti-HLA DSA at MFI ≥ 500 and ≥ 1000 with graft failure, however, increased infection and 1st-year mortality were documented in related haplo-HCT at the MFI cutoffs studied. (REV INVEST CLIN. 2023;75(5):249-58)

Long-Term Efficacy of High-Dose Imatinib in Hispanic Patients Without Access to Second-Generation Tyrosine Kinase Inhibitors Treated in LATAM Centers.

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.

Assessing the Efficacy of Mitoxantrone and Doxorubicin as Frontline Anthracyclines During Induction Therapy of Newly Diagnosed Acute Promyelocytic Leukemia.

BACKGROUND: Therapeutic advances in acute promyelocytic leukemia (APL) have transformed it into today's most curable form of leukemia. However, recommended agents, including arsenic trioxide, idarubicin, or daunorubicin, are not easily available in low-middle-income countries, where outcomes remain suboptimal. We aimed to assess the efficacy and safety of more accessible anthracyclines. METHODS: We conducted a retrospective cohort study including sixty-one patients diagnosed with APL over a 15-year period. Patients received low-dose all-trans retinoic acid (ATRA, 25 mg/m2) with mitoxantrone or doxorubicin as an induction to remission therapy. Groups were compared using the χ2 and Student's t-tests. Kaplan-Meier analysis was used for survival analyses. RESULTS: Thirty (49.18%) patients received mitoxantrone, and 31 (50.82%) received doxorubicin. The median follow-up was 24.6 months (1-146). Twenty-eight (93.3%) patients achieved complete remission (CR) in the mitoxantrone group and 28 (87.1%) in the doxorubicin group (p=0.103), and the median time to CR was 40 and 31 days, respectively. Mitoxantrone had a 6.7% early mortality rate and a 16.7% relapse rate compared with doxorubicin (3.2% and 32.3%, respectively). No differences were found in survival (p = 0.795), hospitalization days (p = 0.261), or adverse events (p = 0.554). CONCLUSIONS: Using mitoxantrone or doxorubicin as induction therapy in newly diagnosed APL is a safe and adequate alternative with comparable outcomes to first-line agents in scenarios where the latter might not be readily available, such as in low-middle-income countries.

Outcomes and survival predictors of Latin American older adults with acute myeloid leukemia: Data from a single center

ABSTRACT Introduction: Acute myeloid leukemia (AML) is most commonly presented in older adults; however, it appears 10 years earlier in Latin American countries. Clinical evolution in older adults from this populations has not been characterized. We analyzed outcomes and survival predictors. Methods: Patients ≥ 55 years old diagnosed with AML at a hematology referral center from 2005 to 2020 receiving intensive chemotherapy (IC), low-dose cytarabine (LDAC) and best supportive care (BSC) were included. Survival analysis included the Kaplan-Meier and Cox models and the cumulative incidence of relapse (CIR). Results: Seventy-five adults were included and the overall survival (OS) was 4.87, 1.67 and 1.16 months, using IC, LDAC and BSC, respectively. The IC led to a higher OS (p < 0.001) and was a protective factor for early death, at a cost of more days spent hospitalized and more non-fatal treatment complications; non-significant differences were found between the LDAC and BSC. Eight (10.7%) patients underwent hematopoietic cell transplantation, with a higher OS (p = 0.013). Twenty (26.7%) patients achieved complete remission; 12 (60%) relapsed with a 6-month CIR of 57.9% in those < 70 years old vs. 86.5% in those ≥ 70 years old, p = 0.034. Multivariate analysis showed the white blood cell count (WBC) and IC had a significant impact on the patient survival, whereas chronological age and the Charlson comorbidity index (CCI) did not. Conclusion: AML in low-middle income countries demands a different approach; the IC improves survival, even with a high incidence of relapse, and should be offered as first-line treatment. Eligibility criteria should include WBC and a multidimensional evaluation. The age per se and the CCI should not be exclusion criteria to consider IC.

Infection-related mortality after HLA-identical and haploidentical hematopoietic cell transplantation using reduced-intensity conditioning in an outpatient setting.

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.

Outcomes and survival predictors of Latin American older adults with acute myeloid leukemia: Data from a single center.

INTRODUCTION: Acute myeloid leukemia (AML) is most commonly presented in older adults; however, it appears 10 years earlier in Latin American countries. Clinical evolution in older adults from this populations has not been characterized. We analyzed outcomes and survival predictors. METHODS: Patients ≥ 55 years old diagnosed with AML at a hematology referral center from 2005 to 2020 receiving intensive chemotherapy (IC), low-dose cytarabine (LDAC) and best supportive care (BSC) were included. Survival analysis included the Kaplan-Meier and Cox models and the cumulative incidence of relapse (CIR). RESULTS: Seventy-five adults were included and the overall survival (OS) was 4.87, 1.67 and 1.16 months, using IC, LDAC and BSC, respectively. The IC led to a higher OS (p < 0.001) and was a protective factor for early death, at a cost of more days spent hospitalized and more non-fatal treatment complications; non-significant differences were found between the LDAC and BSC. Eight (10.7%) patients underwent hematopoietic cell transplantation, with a higher OS (p = 0.013). Twenty (26.7%) patients achieved complete remission; 12 (60%) relapsed with a 6-month CIR of 57.9% in those < 70 years old vs. 86.5% in those ≥ 70 years old, p = 0.034. Multivariate analysis showed the white blood cell count (WBC) and IC had a significant impact on the patient survival, whereas chronological age and the Charlson comorbidity index (CCI) did not. CONCLUSION: AML in low-middle income countries demands a different approach; the IC improves survival, even with a high incidence of relapse, and should be offered as first-line treatment. Eligibility criteria should include WBC and a multidimensional evaluation. The age per se and the CCI should not be exclusion criteria to consider IC.

Lactate dehydrogenase as a hematopoietic stem cell mobilization biomarker in autologous transplantation.

INTRODUCTION: Pre-apheresis peripheral blood CD34+ cell count (PBCD34+) is the most important predictor of good cell mobilization before hematopoietic stem cell transplantation, albeit flow cytometry is not always immediately available. Identification of surrogate markers can be useful. The CD34+ cells proliferate after mobilization, resulting in elevated lactate dehydrogenase (LDH) activity and correlating with the PBCD34+ count. OBJECTIVE: To determine the LDH cut-off value at which adequate CD34+ cell mobilization is achieved and its diagnostic yield. MATERIALS AND METHODS: A total of 103 patients who received an autologous stem cell transplantation (ASCT) between January 2015 and January 2020 were included. Demographic and laboratory characteristics were obtained, including complete blood count, pre-apheresis PBCD34+ and LDH levels. Receiver operating characteristic (ROC) curves were performed to identify the optimal serum LDH activity cut-off points for ≥ 2 and ≥ 4 × 106 cells/kg post-mobilization CD34+ count and their diagnostic yield. RESULTS: A post-mobilization serum LDH cut-off value of 462 U/L yielded a sensitivity (Se) = 86.8% (positive predictive value [PPV] = 72.7%), a pre- and post-mobilization serum LDH difference cut-off value of 387 U/L, an Se = 45.7% (PPV = 97%) and an LDH ratio of 2.46, with an Se = 47.1% (PPV = 97%) for an optimal mobilization count (CD34+ ≥ 4 × 106). CONCLUSION: The LDH measurement represents a fast and affordable way to predict PBCD34+ mobilization in cases where flow cytometry is not immediately available. According to the LDH diagnostic yield, it could be used as a surrogate marker in transplant centers, supporting the CD34+ count, which remains the gold standard.

Treatment of Ph-Negative Acute Lymphoblastic Leukemia in Adolescents and Young Adults with an Affordable Outpatient Pediatric Regimen.

BACKGROUND: B-cell acute lymphoblastic leukemia is frequent in Hispanic adolescents and young adults. Outcomes of implementation of pediatric-inspired regimens in low-and middle-income countries are not well known. METHODS: In this study we treated 94 adolescents and young adults with a local BFM regimen designed to be affordable with the use of native L-asparaginase and mitoxantrone administered in an outpatient fashion, and the of BCR/ABL and measurable residual disease (MRD) determined by high sensitivity flow cytometry for risk stratification. RESULTS: Induction mortality was 11%; 25% of patients had to abandon treatment or be transferred to another health system. Two-year overall (OS) and event free survival (EFS) were 61.5% and 49.8%, MRD-negative patients had a 24-month OS of 85.6% vs. 69.6% (p = .024) and EFS of 76% vs. 45.5% (p = .004). Patients older than 40 years and those who abandoned treatment had worse EFS. Overall drug costs in our regimen were 52% lower than those of CALGB10403. CONCLUSION: The treatment of AYAs with ALL with an outpatient focus was implemented successfully at a reduced cost. Genetic risk assessment, treatment abandonment and lack of access to novel therapies remain major barriers for improving outcomes.

Monthly variation in diagnosis of acute lymphoblastic leukemia and survival outcome in children and adults: 15-year trends at a single center

ABSTRACT Background: The date of acute lymphoblastic leukemia (ALL) diagnosis has been studied regarding potential etiologic roles with contrasting results and the issue remains controversial. The principal aim of this study was to analyze monthly variation of ALL diagnosis in a large homogenous Hispanic Latin American cohort over 15 years; its association with survival rates was also assessed. Methods: Clinical files and electronic records of 501 consecutive patients of all ages with ALL in northeastern Mexico over the years of 2004-2018 were scrutinized. Patients were divided into children <18 and adults >18 years. The Chi-square heterogeneity analysis was used to test for non-uniform variation. The Poisson regression analysis was used to fit sinusoidal (harmonic) models to the data, using the month of diagnosis as a covariate in a separate model. Results: During the study period 363 children (72.5%) and 138 adults (27.5%) (p < 0.001) were diagnosed with ALL. Heterogeneity across the months of diagnosis was confirmed (p = 0.019) and the Poisson regression analysis confirmed a significant monthly variation (p < 0.001) (95% CI, 3.024-3.745), a higher annual peak being observed in the month of March (p = 0.002), followed by a second peak in October (p = 0.026). The five-year OS for children was 68.2% (95% CI, 67.64-68.74) and for adults, 43.7% (95% CI, 42.67-44.71) (p < 0.001). No significant association between the month of diagnosis and OS was found (p = 0.789). Conclusion: The monthly variation of ALL diagnosis was documented; these results confirm the heterogeneous behavior of the disease and appear to be consistent with an interplay of environmental and biologic factors. Further studies are needed to examine putative candidate agents.

Alternatives for managing patients with newly diagnosed immune thrombocytopenia: a narrative review.

INTRODUCTION: Primary immune thrombocytopenia (ITP) is an acquired bleeding disorder. Conventionally, first-line ITP therapy aims to obtain a rapid response and stop or decrease the risk of bleeding by increasing the platelet count. At this point, the duration of the response, the tolerability, and the long-term safety of pharmacologic interventions are considered less of a priority. Combination treatments that simultaneously address multiple disease mechanisms are an attractive strategy to increase efficacy in acute ITP therapy. In this review, we discuss the treatment of newly diagnosed ITP patients, emphasizing the use of new combinations to benefit from their synergy. AREAS COVERED: This article summarizes conventional treatment, recent and novel combinations, and COVID-19 management recommendations of newly diagnosed ITP patients. EXPERT OPINION: The key areas for improvement consider the long-term effects of conventional first-line therapy, reducing relapse rates, and extending responses to achieve long-term remission. Although corticosteroids remain a first-line therapy, restricting their use to avoid toxicity and the increasing use of rituximab and TPO-RAs in the first three months after diagnosis open the landscape for future interventions in frontline therapy for ITP. First-line therapy intensification or synergistic drug combination offers a potential and realistic shift in future treatment guidelines.

Outpatient haploidentical hematopoietic stem cell transplant using post-transplant cyclophosphamide and incidence of hemorrhagic cystitis

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.

Hematopoietic stem cell transplantation for uncommon immune-mediated neurological disorders: A literature review.

BACKGROUND: Chronic inflammatory demyelinating polyneuropathy (CIDP), stiff-person syndrome (SPS), neuromyelitis optica spectrum disorders (NMOSD) and severe refractory myasthenia gravis (MG) are immune-mediated neurological diseases that severely affect patients' functionality and quality of life, with a considerable percentage undergoing relapse or not responding to conventional treatment options. Autologous hematopoietic stem cell transplantation (auto-HSCT) has emerged as a potential second-line treatment alternative. METHODS: We performed a literature review in PubMed/Medline, EMBASE, Web of Science and Cochrane Library from inception to September 2021 of reported cases and studies of CIDP, SPS, NMOSD and MG that underwent HSCT as a treatment option. RESULTS: A total of 173 patients who underwent HSCT were found, including 32 patients described in case reports and 60 in a phase 2 clinical trial with CIDP, 29 patients with SPS, 42 patients with NMOSD and 10 patients with refractory MG. Complete remission was documented in 68/92 patients with CIDP, 13/29 with SPS and 10/10 with MG. From the NMOSD cases, 24/42 were relapse-free at last follow-up, with 13/33 having negative anti-AQ4 antibodies after HSCT. From all the included studies, only 8/173 patients received an allogeneic HSCT, 4/8 after a failed auto-HSCT. All showed clinical improvement and disease remission. CONCLUSION: HSCT has the potential to induce long-term remission in patients with CIDP, NMOSD, SPS or MG with adequate safety and tolerability. Collaboration between centers is needed to implement larger, homogeneous prospective studies, focusing on immunological correlates of favorable long-term response.

Monthly variation in diagnosis of acute lymphoblastic leukemia and survival outcome in children and adults: 15-year trends at a single center.

BACKGROUND: The date of acute lymphoblastic leukemia (ALL) diagnosis has been studied regarding potential etiologic roles with contrasting results and the issue remains controversial. The principal aim of this study was to analyze monthly variation of ALL diagnosis in a large homogenous Hispanic Latin American cohort over 15 years; its association with survival rates was also assessed. METHODS: Clinical files and electronic records of 501 consecutive patients of all ages with ALL in northeastern Mexico over the years of 2004-2018 were scrutinized. Patients were divided into children ≤18 and adults >18 years. The Chi-square heterogeneity analysis was used to test for non-uniform variation. The Poisson regression analysis was used to fit sinusoidal (harmonic) models to the data, using the month of diagnosis as a covariate in a separate model. RESULTS: During the study period 363 children (72.5%) and 138 adults (27.5%) (p < 0.001) were diagnosed with ALL. Heterogeneity across the months of diagnosis was confirmed (p = 0.019) and the Poisson regression analysis confirmed a significant monthly variation (p < 0.001) (95% CI, 3.024-3.745), a higher annual peak being observed in the month of March (p = 0.002), followed by a second peak in October (p = 0.026). The five-year OS for children was 68.2% (95% CI, 67.64-68.74) and for adults, 43.7% (95% CI, 42.67-44.71) (p < 0.001). No significant association between the month of diagnosis and OS was found (p = 0.789). CONCLUSION: The monthly variation of ALL diagnosis was documented; these results confirm the heterogeneous behavior of the disease and appear to be consistent with an interplay of environmental and biologic factors. Further studies are needed to examine putative candidate agents.

Outpatient haploidentical hematopoietic stem cell transplant using post-transplant cyclophosphamide and incidence of hemorrhagic cystitis.

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.