Trasplante cardíaco y autólogo de células progenitoras hematopoyéticas en pacientes con amiloidosis AL / Cardiac and autologous stem cell transplantation hematopoietic in patients with AL amyloidosis

Resumen Objetivo: Describir la evolución de las cadenas livianas libres séricas (CLL) en el período comprendido entre el trasplante cardíaco ortotópico (TCO) y el trasplante de células progenitoras hematopoyéticas (TCPH), la respuesta hematológica al año tras el TCPH y el tratamiento quimioterápico e inmunosupresor en pacientes con amiloidosis AL. Método: Serie de casos de pacientes consecutivos con diagnóstico de amiloidosis AL que recibieron TCO seguido de TCPH del Registro Institucional de Amiloidosis del Hospital Italiano de Buenos Aires, entre enero de 2010 y noviembre de 2021. Se reportaron los valores de CLL entre trasplantes y al año del TCPH. Las variables cuantitativas se describieron como mediana e intervalo intercuartil, y las variables categóricas como frecuencias absolutas y relativas. Resultados: De 106 pacientes con amiloidosis AL, seis tuvieron TCO seguido de TCPH. La mediana de edad fue de 55 años. La mayoría eran hombres (n = 5). En el período entre trasplantes, la CLL involucrada disminuyó en dos pacientes y se mantuvo estable en tres. Todos lograron la remisión hematológica completa al año del TCPH. Un solo paciente presentó recaída en el órgano sólido trasplantado. Tacrolimus, micofenolato de mofetilo y corticoides fue el esquema inmunosupresor utilizado después del TCO. Conclusiones: El TCO representa una opción de tratamiento en pacientes con falla cardíaca grave por amiloidosis, permitiendo luego un tratamiento intensivo con quimioterapia de inducción y TCPH. Si bien faltan estudios, la terapia inmunosupresora después del TCO podría tener algún efecto sobre las células plasmáticas clonales.

Abstract Objective: To describe the evolution of serum free light chains (FLC) in the period between orthotopic heart transplantation (OHT) and autologous stem cell transplantation (ASCT), the hematological response one year after ASCT and chemotherapy and immunosuppressive treatment in patients with AL amyloidosis. Method: Case series of consecutive patients diagnosed with AL amyloidosis who received OHT followed by ASCT from the Institutional Registry of Amyloidosis of the Italian Hospital of Buenos Aires, between January 2010 and November 2021. FLC values between transplants and at year post ASCT. Quantitative variables were described with their median and interquartile range. Categorical variables as absolute and relative frequencies. Results: Of 106 patients with AL amyloidosis, 6 had an OHT followed by ASCT. The median age was 55 years. Most were men (n = 5). In the period between transplants, the involved CLL decreased in two patients and remained stable in three. All achieved complete hematologic remission 1 year after ASCT. A single patient presented relapse in the transplanted solid organ. Tacrolimus, mycophenolate mofetil, and corticosteroids were the immunosuppressive regimen used after OHT. Conclusions: OHT represents a treatment option in patients with severe heart failure due to amyloidosis, allowing later intensive treatment with induction chemotherapy and ASCT. Although studies are lacking, immunosuppressive therapy after OHT might have some effect on clonal plasma cells.

Cardiac and autologous stem cell transplantation hematopoietic in patients with AL amyloidosis.

OBJECTIVE: To describe the evolution of serum free light chains (FLC) in the period between orthotopic heart transplantation (OHT) and autologous stem cell transplantation (ASCT), the hematological response one year after ASCT and chemotherapy and immunosuppressive treatment in patients with AL amyloidosis. METHOD: Case series of consecutive patients diagnosed with AL amyloidosis who received OHT followed by ASCT from the Institutional Registry of Amyloidosis of the Italian Hospital of Buenos Aires, between January 2010 and November 2021. FLC values between transplants and at year post ASCT. Quantitative variables were described with their median and interquartile range. Categorical variables as absolute and relative frequencies. RESULTS: Of 106 patients with AL amyloidosis, 6 had an OHT followed by ASCT. The median age was 55 years. Most were men (n = 5). In the period between transplants, the involved CLL decreased in two patients and remained stable in three. All achieved complete hematologic remission 1 year after ASCT. A single patient presented relapse in the transplanted solid organ. Tacrolimus, mycophenolate mofetil, and corticosteroids were the immunosuppressive regimen used after OHT. CONCLUSIONS: OHT represents a treatment option in patients with severe heart failure due to amyloidosis, allowing later intensive treatment with induction chemotherapy and ASCT. Although studies are lacking, immunosuppressive therapy after OHT might have some effect on clonal plasma cells.

OBJETIVO: Describir la evolución de las cadenas livianas libres séricas (CLL) en el período comprendido entre el trasplante cardíaco ortotópico (TCO) y el trasplante de células progenitoras hematopoyéticas (TCPH), la respuesta hematológica al año tras el TCPH y el tratamiento quimioterápico e inmunosupresor en pacientes con amiloidosis AL. MÉTODO: Serie de casos de pacientes consecutivos con diagnóstico de amiloidosis AL que recibieron TCO seguido de TCPH del Registro Institucional de Amiloidosis del Hospital Italiano de Buenos Aires, entre enero de 2010 y noviembre de 2021. Se reportaron los valores de CLL entre trasplantes y al año del TCPH. Las variables cuantitativas se describieron como mediana e intervalo intercuartil, y las variables categóricas como frecuencias absolutas y relativas. RESULTADOS: De 106 pacientes con amiloidosis AL, seis tuvieron TCO seguido de TCPH. La mediana de edad fue de 55 años. La mayoría eran hombres (n = 5). En el período entre trasplantes, la CLL involucrada disminuyó en dos pacientes y se mantuvo estable en tres. Todos lograron la remisión hematológica completa al año del TCPH. Un solo paciente presentó recaída en el órgano sólido trasplantado. Tacrolimus, micofenolato de mofetilo y corticoides fue el esquema inmunosupresor utilizado después del TCO. CONCLUSIONES: El TCO representa una opción de tratamiento en pacientes con falla cardíaca grave por amiloidosis, permitiendo luego un tratamiento intensivo con quimioterapia de inducción y TCPH. Si bien faltan estudios, la terapia inmunosupresora después del TCO podría tener algún efecto sobre las células plasmáticas clonales.

Decrease in Mortality from Sepsis: Impact of the Multidisciplinary Program for the Hematologic Patient at Very High Risk.

A program for the hematologic patient at very high risk of infections (HAR, from its initials in Spanish) was implemented, based on a multidisciplinary team and six measures intended to reduce the colonization and subsequent sepsis by multidrug-resistant organisms (MDRO). We aimed at evaluating the effectiveness of the HAR program in terms of MDRO infections mainly caused by Klebsiella pneumoniae carbapenemase-producing and multidrug-resistant Pseudomona aeruginosa, and sepsis-related mortality. We established retrospective comparisons between the pre-HAR period (2016-2018) and the post-HAR period (2018-2019), in patients who received a hematopoietic stem cell transplant (HSCT) and/or intensive chemotherapy to treat non-M3 acute myeloid leukemia (CH-AML). We included 262 patients: 176 pre-HAR and 86 post-HAR. MDRO infection was 4.6% at 30 days and 6.1% at 90 days (all the cases during the pre-HAR period). Sepsis-related mortality was 6.5%, considering a median follow-up of 608 days: 6.1% in the HSCT group and 12.4% in the CH-AML group (p = 0.306). Sepsis-related mortality was 8.7% in the pre-HAR period and 0% in the post-HAR period (p = 0.014). The implementation of this multidisciplinary program based in preventive measures and the appropriate use of antibiotics enabled a decrease in sepsis-related mortality in very high-risk hematologic patients.

Nonimmune-acquired factor XIII deficiency: a cause of high volume and delayed postoperative hemorrhage.

: Factor XIII (FXIII) levels may decrease because of surgical consumption. Acquired FXIII deficiency could be a cause of postoperative hemorrhage usually underdiagnosed in clinical practice. To determine the diagnosis confirmation rate of acquired FXIII deficiency in postsurgical patients with clinical suspicion and to compare the characteristics and evolution of patients with or without FXIII deficiency. We performed a retrospective cohort study, which included 49 inpatients who were attended at our university hospital from 2014 to 2018 with suspicion of acquired FXIII deficiency because of disproportionate postoperative hemorrhage. FXIIIA levels less than 50% was considered a deficiency. Persistence of bleeding for more than 48 h, drop in hematocrit points, red blood cells transfused units, hemoglobin levels 12-36 h after bleeding, and time elapsed from the procedure to the bleeding were assessed as outcome variables. Logistic regression was employed for both univariate and multivariate analyses. Of the 49 patients included, 27(55%) had FXIII deficiency, with a median level of 34% [interquartile range (IQR) 19-42]. Abdominal surgery was the most common [n = 21 (43%)]. All patients had routine coagulation tests within the hemostatic range. FXIII deficiency was associated with a drop of more than 4 points in hematocrit [OR 59.69 (95% CI 4.71-755.30)], red blood transfused units >2 [OR 45.38 (95% CI 3.48-590.65)], and delayed bleeding >36 h after surgery [OR 100.90 (95% CI 3.78-2695.40)]. Plasma-derived FXIII concentrate was administered to eight patients with life-threatening bleeding with resolution within 24 h. Only one deficient patient died from bleeding. FXIII levels were measured 15 days after diagnosis or more in 20 out of 27 deficient patients, with normal results. Acquired FXIII deficiency may be a frequent underdiagnosed entity that should be considered when high-volume and delayed postoperative hemorrhage is present in patients with hemostatic routine coagulation test results.

Haploidentical transplant in adult patients with acute lymphoblastic leukemia in Argentina: a comparison with matched related and unrelated donors.

We aimed at analyzing the outcome of allogeneic stem cell transplant (ASCT) in adult patients with acute lymphoblastic leukemia (ALL), comparing Haploidentical (Haplo) with HLA-matched (sibling and unrelated) donors. Between 2008 and 2017, we collected data from 236 patients (median age 31 years; range 16-64; 90% HCT-CI 0-1) who underwent unmanipulated ASCT in first complete remission and subsequent remissions in 15 Argentinian centers. Donors were HLA-matched (n = 175; 74%) and Haplo (n = 61; 26%). Two-year overall survival (OS) was 55% (95% CI 47-63) for the HLA-matched group and 49% (95% CI 34-62) for the Haplo group (p = 0.351). For OS, crude HR, adjusted HR for covariates (HR 1.24; 95% CI 0.77-1.99; p = 0.363) and HR including a propensity score in the model (HR 1.22; 95% CI 0.71-2.08; p = 0.414) showed no impact of donor category on the OS. No difference was found in terms of nonrelapse mortality, relapse, leukemia-free survival, and grade 3-4 acute graft-versus-host disease (GVHD); 2-year incidence of chronic GVHD was higher in HLA-matched vs Haplo group (p = 0.028). Patients with ALL who underwent ASCT were young subjects with low HCT-CI. In this setting, a Haplo donor represents an alternative widely available in the absence of an HLA-matched donor. Relapse remains a challenge for all donor categories.

Hematopoietic Cell Transplantation-Specific Comorbidity Index Predicts Morbidity and Mortality in Autologous Stem Cell Transplantation.

The hematopoietic cell transplantation-specific comorbidity index (HCT-CI) score is a useful tool to assess the risk for nonrelapse mortality (NRM) after allogeneic hematopoietic stem cell transplantation. Although the HCT-CI has been investigated in autologous stem cell transplantation (ASCT), its use is limited. To improve on the current use of the HCT-CI score on the morbidity and mortality after ASCT, we assessed the 100-day morbidity defined as orotracheal intubation (OTI), dialysis or shock (vasopressors need), 100-day NRM, early composite morbidity-mortality (combined endpoint that included any previous endpoints), and long-term NRM. We retrospectively reviewed a cohort of 1730 records of adult patients who received an ASCT in Argentinean center's between October 2002 and August 2016. Median follow-up was 1.15 years, and median age was 53 years. Diseases were multiple myeloma (48%), non-Hodgkin lymphoma (27%), and Hodgkin lymphoma (17%); 51% were in complete or partial remission; and 13% received ≥ 3 chemotherapy lines before transplant (heavily pretreated). Early NRM (100-day) was 2.7%, 5.4% required OTI, 4.5% required vasopressors, and 2.1% dialysis, with an early composite morbidity-mortality of 6.8%. Long-term (1 and 3 years) NRM was 4% and 5.2% and overall survival 89% and 77%, respectively. High-risk HCT-CI patients had a significant increase in 100-day NRM compared with intermediate and low risk (6.1% versus 3.4% versus 1.8%, respectively; P = .002), OTI (11% versus 6% versus 4%, P = .001), shock (8.7% versus 5.8% versus 3%, P = .001), early composite morbidity-mortality (13% versus 9 % versus 4.7%, P < .001), and long-term NRM (1 year, 7.7% versus 4% versus 3.3%; and 3 years, 10.8% versus 4% versus 4.8%, respectively; P = .002). After multivariate analysis these outcomes remained significant: early composite morbidity-mortality (odds ratio [95% confidence interval] compared with low risk: intermediate risk 2.1 [1.3 to 3.5] and high risk 3.3 [1.9 to 5.9]) and NRM (hazard ratio [95% confidence interval] compared with low risk: intermediate risk .97 [.8 to 2.4] and high risk 3.05 [1.3 to 4.5]). No significant impact was observed in overall survival. Other than comorbidities, significant impact was observed for heavily pretreated patients, age ≥ 55 years, non-Hodgkin lymphoma, and bendamustine-etoposide-citarabine-melphalan conditioning. We confirmed that the HCT-CI had a significant impact on NRM after ASCT, and these findings are mainly due to early toxicity express as 100-day NRM and the 3 main morbidity outcomes as well as the composite endpoint.

[Treatment conditioning variables in elderly patients with acute myeloid leukemia. An institutional experience]. / Variables condicionantes del tratamiento en pacientes añosos con leucemia mieloide aguda. Experiencia institucional.

Patients over 60 years old with acute myeloid leukemia (AML) have a worse prognosis due to several factors that determine the therapeutic outcome. The main predictors of mortality in patients with AML reported in the literature were analyzed in our population. The primary objective was to analyze overall survival. The secondary objective was to determine treatment-related mortality, defined as death within eight weeks of starting treatment. It was designed as a retrospective study. A total of 133 treatment naive patients were included, from January 1991 to August 2014. The adjusted analysis showed that the most important variables to determine overall survival were the WBC count = 30 000 at diagnosis [adjusted HR 2.19 (1.06-4.53), p = 0.03)] and the Performance Status (ECOG) 3 or 4 [aHR 4.63 (1.69-12.68), p < 0.001)]. Performance Status 3-4 was the only variable that conditioned treatment related mortality, showing in the univariate analysis an OR 5.44 (CI 1.93-15.28, p < 0.001). It was also the only variable that kept its statistical power in the multivariate analysis adjusted OR (aOR) 12.40 (IC 1.12-137.17, p = 0.04). The inherent poor outcome in elderly patients diagnosed with AML is not fully understood. The best way of assessing these elderly patients should probably include not only age but the best way of assessing these elderly patients should probably include not only age but laboratory, genetic and molecular studies. Especially designed comorbidity and fragility indices should be included, along with functional status. Leukocytosis and poor quality of life were identified as the most powerfull factors for predicting mortality in our study.

Variables condicionantes del tratamiento en pacientes añosos con leucemia mieloide aguda: Experiencia institucional / Treatment conditioning variables in elderly patients with acute myeloid leukemia. An institutional experience

Los mayores de 60 años con leucemia mieloide aguda (LMA) tienen peor pronóstico que el resto de los pacientes. En la literatura se expresan diferentes factores que podrían condicionar su supervivencia. Se propuso determinar cuáles fueron los principales determinantes de supervivencia global en nuestra población; y como objetivo secundario cuáles estaban vinculados con mortalidad temprana, entendida la misma como muerte dentro de las ocho semanas de iniciado el tratamiento. Para ello se diseñó un estudio de cohorte retrospectivo que incluyó 133 pacientes no tratados previamente. El análisis ajustado a covariables demostró que las variables de mayor peso para determinar supervivencia global fueron el recuento leucocitario ≥ 30 000 al diagnóstico [HR ajustado 2.19 (1.06-4.53), p = 0.03)] y el estado general (ECOG) 3 o 4 [HRa 4.63 (1.69-12.68), p < 0.001)]. En cuanto a mortalidad relacionada al tratamiento, el estado general (ECOG) 3-4 mostró ser la única variable que mantuvo su poder estadístico en el análisis multivariado con OR ajustado (ORa) 12.40 (IC 1.12-137.17, p = 0.04). El mal resultado inherente a los pacientes añosos con diagnóstico de LMA no se entiende por completo aún. Probablemente la mejor forma de evaluarlos debería tener en cuenta no solo la edad, sino también resultados de laboratorio, de estudios genéticos y moleculares, utilizando índices específicos de comorbilidad, estado general y alguna evaluación geriátrica de fragilidad. Este estudio identificó que la leucocitosis y el mal estado general fueron los factores que mostraron un mayor poder en la predicción de la mortalidad.

Patients over 60 years old with acute myeloid leukemia (AML) have a worse prognosis due to several factors that determine the therapeutic outcome. The main predictors of mortality in patients with AML reported in the literature were analyzed in our population. The primary objective was to analyze overall survival. The secondary objective was to determine treatment-related mortality, defined as death within eight weeks of starting treatment. It was designed as a retrospective study. A total of 133 treatment naive patients were included, from January 1991 to August 2014. The adjusted analysis showed that the most important variables to determine overall survival were the WBC count ≥ 30 000 at diagnosis [adjusted HR 2.19 (1.06-4.53), p = 0.03)] and the Performance Status (ECOG) 3 or 4 [aHR 4.63 (1.69-12.68), p < 0.001)]. Performance Status 3-4 was the only variable that conditioned treatment related mortality, showing in the univariate analysis an OR 5.44 (CI 1.93-15.28, p < 0.001). It was also the only variable that kept its statistical power in the multivariate analysis adjusted OR (aOR) 12.40 (IC 1.12-137.17, p = 0.04). The inherent poor outcome in elderly patients diagnosed with AML is not fully understood. The best way of assessing these elderly patients should probably include not only age but the best way of assessing these elderly patients should probably include not only age but laboratory, genetic and molecular studies. Especially designed comorbidity and fragility indices should be included, along with functional status. Leukocytosis and poor quality of life were identified as the most powerfull factors for predicting mortality in our study.

Proatherogenic disturbances in lipoprotein profile, associated enzymes and transfer proteins in women with iron deficiency anaemia.

OBJECTIVE: To characterize the lipid-related atherogenic risk factors in iron deficiency anaemia (IDA) patients. DESIGN AND METHODS: Twenty IDA women were compared to healthy age-matched controls. Lipoprotein profile, cholesteryl ester transfer protein (CETP), paraoxonase (PON) 1 and lipoprotein-associated phospholipase A(2) (LpPLA(2)) activities and plasma levels of oxidized-LDL were evaluated. RESULTS: Triglycerides were higher (median [range]) (1.0 [0.5-1.9] vs. 0.7 [0.5-1.5] mmol/L, p<0.05) and HDL-C lower (mean + or - SD) (1.3 + or - 0.3 vs. 1.6 + or - 0.4 mmol/L, p<0.01) in the patients group. CETP (197 + or - 29% vs. 151 + or - 29% mL(-1) h(-1), p<0.001), PON 1 (122 + or - 17 vs. 140 + or - 33 micromol mL(-1) min(-1), p<0.05) and LpPLA(2) (9.6 + or - 2.0 vs. 8.1 + or - 1.7 micromol mL(-1) h(-1), p<0.05) activities were different in IDA women. No difference was observed in oxidized-LDL. Haemoglobin correlated negatively with triglycerides (r=-0.35, p<0.05), CETP (r=-0.62, p<0.001) and LpPLA(2) (r=-0.34, p<0.05), while ferritin was positively associated with HDL-C (r=0.39, p<0.05) and inversely with CETP (r=-0.49, p<0.005). CONCLUSION: The alterations in lipoprotein profile, CETP, PON 1 and LpPLA(2) activities described in the present study indicate that non-treated IDA might represent a proatherogenic state.