Is Iron Overload Associated with Worse Outcomes in Patients with Chronic Liver Disease Undergoing Liver Transplantation?

ABSTRACT Background: Iron overload is frequent in patients with chronic liver disease, associated with shorter survival after liver transplantation in patients with hereditary hemochromatosis. Its effect on patients without hereditary hemochromatosis is unclear. The aim of the study was to study the clinical impact of iron overload in patients who underwent liver transplantation at an academic tertiary referral center. Methods: We performed a retrospective cohort study including all patients without hereditary hemochromatosis who underwent liver transplantation from 2015 to 2017 at an academic tertiary referral center in Mexico City. Explant liver biopsies were reprocessed to obtain the histochemical hepatic iron index, considering a score ≥ 0.15 as iron overload. Baseline characteristics were compared between patients with and without iron overload. Survival was estimated using the Kaplan-Meier method, compared with the log-rank test and the Cox proportional hazards model. Results: Of 105 patients included, 45% had iron overload. Viral and metabolic etiologies, alcohol consumption, and obesity were more frequent in patients with iron overload than in those without iron overload (43% vs. 21%, 32% vs. 22%, p = 0.011; 34% vs. 9%, p = 0.001; and 32% vs. 12%, p = 0.013, respectively). Eight patients died within 90 days after liver transplantation (one with iron overload). Complication rate was higher in patients with iron overload versus those without iron overload (223 vs. 93 events/100 person-months; median time to any complication of 2 vs. 3 days, p = 0.043), without differences in complication type. Fatality rate was lower in patients with iron overload versus those without iron overload (0.7 vs. 4.5 deaths/100 person-months, p = 0.055). Conclusion: Detecting iron overload might identify patients at risk of early complications after liver transplantation. Further studies are required to understand the role of iron overload in survival.

Cost-effectiveness of the regimen proposed by the International Consortium on Acute Promyelocytic Leukemia for the treatment of newly diagnosed patients with Acute Promyelocytic Leukemia

ABSTRACT Introduction: We performed cost-effectiveness and cost-utility analyses of the modified International Consortium on Acute Promyelocytic Leukemia protocol in Mexico for the treatment of acute promyelocytic leukemia Acute Promyelocytic Leukemia. Methods: We performed a three-state Markov analysis: stable disease (first line complete response [CR]), disease event (relapse, second line response and CR) and death. The modified IC-APL protocol is composed of three phases: induction, consolidation and maintenance. Cost and outcomes were used to calculate incremental cost-effectiveness ratios (ICERs); quality-adjusted life-years were used to calculate incremental cost-utility ratios (ICURs). Results: The CR was achieved in 18 patients (90%), treated with the IC-APL protocol as the first-line option; one patient (5%) died in induction, another one never achieved CR (5%); of the 18 patients that achieved CR, 1 relapsed (5.5%). The median treatment cost of the IC-APL protocol was $21,523 USD. The average life-year in our study was 7.8 years, while the average quality-adjusted life-year (QALY) was 6.1 years. When comparing the ICER between the IC-APL and the all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) protocols, we found the different costs of $6497, $19,133 and $17,123 USD in Italy, the USA and Canada, respectively. In relation to the ICUR, we found the different costs to be $13,955 and $11,979 USD in the USA and Canada, respectively. Conclusion: Taking into account the similar response rates, lower cost and easy access to the modified IC-APL regimen, we consider it a cost-effective and cost-utility protocol, deeming it the treatment of choice for our population.

Consideraciones terapéuticas en pacientes con leucemia aguda en la era COVID-19 / Therapeutic approach in acute leukemia patients in the COVID-19 era

Resumen La pandemia por enfermedad por coronavirus 2019 (COVID-19), causada por el coronavirus 2 del síndrome respiratorio agudo grave (SARS-CoV-2), ha afectado ya a 180 países. Los pacientes con cáncer/inmunosupresión a mayor edad tienen más riesgo de presentar formas graves de la enfermedad. Los pacientes con leucemia aguda son un reto para el manejo durante la pandemia. Las recomendaciones para el manejo de estos pacientes están basadas en opinión de expertos. Se trata de una población en la que hay que realizar de forma sistemática pruebas de reacción en cadena de la polimerasa para SARS-CoV-2 y diferir en la medida de lo posible la quimioterapia citotóxica en los pacientes que resulten positivos. Por otro lado, algunos de los fármacos frecuentemente utilizados como los corticosteroides, el rituximab o la asparaginasa, pueden potencialmente complicar el curso del COVID-19, por lo que se deberá de considerar diferirlos o ajustarlos en poblaciones de mayor riesgo. De la misma forma, tomando en cuenta las particularidades de cada centro, en ciertos casos se podrá considerar dar preferencia a los esquemas de tratamiento ambulatorios que nos permitan además disminuir el requerimiento transfusional. Finalmente, muchos de los pacientes con leucemia aguda son candidatos para recibir trasplante alogénico de células progenitoras hematopoyéticas (aloTCPH). Debe tomarse en cuenta la limitación de los espacios en terapia intensiva, así como el grado de inmunosupresión derivado del trasplante. La recomendación es no diferir los aloTCPH en los pacientes con una mayor riesgo de recaída de la enfermedad. Más adelante conoceremos las consecuencias de las modificaciones en el tratamiento derivadas de la pandemia sobre la leucemia.

Abstract The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has already affected 180 countries. Older patients and patients with cancer or immunosuppression are at greater risk of severe forms of the disease. Patients with acute leukemia are challenging to manage during the pandemic. Recommendations for the management of these patients are based on expert opinion. This is a population in which polymerase chain reaction tests for SARS-CoV-2 must be performed routinely and cytotoxic chemotherapy should be deferred as far as possible in positive patients. On the other hand, some of the frequently used drugs such as corticosteroids, rituximab or asparaginase, can potentially complicate the course of COVID-19, so consideration should be given to deferring or adjusting them in higher-risk populations. In the same way, considering the particularities of each center, in certain cases it may be reasonable to give preference to outpatient regimens that also allow us to decrease the transfusion requirement. Finally, many of the patients with acute leukemia are candidates to receive allogeneic hematopoietic stem cell transplantation (alloHSCT). The limitation of the spaces in intensive care units must be considered, as well as the degree of immunosuppression derived from the transplant. The recommendation is not to defer alloHSCT in patients with an increased risk of relapse. Later, we will learn about the consequences on of the modifications in treatment on leukemia derived from the pandemic.

Survival and treatment response in adults with acute promyelocytic leukemia treated with a modified International Consortium on Acute Promyelocytic Leukemia protocol

ABSTRACT Acute promyelocytic leukemia has good prognosis in view of the high complete remission and survival rates achieved with therapies containing all-trans retinoic acid or arsenic trioxide. However, there is a significant risk of death during induction due to hemorrhage secondary to disseminated intravascular coagulation. This has contributed to a gap in the prognosis of patients between developed and developing countries. The International Consortium on Acute Promyelocytic Leukemia was created in 2005 and proposed a treatment protocol based on daunorubicin and all-trans retinoic acid stratified by risk geared toward developing countries. Herein are presented the results from the first patient cohort treated in a single developing country hospital employing a slightly modified version of the International Consortium protocol in a real life setting. Twenty patients with acute promyelocytic leukemia were enrolled: 27.8% had low-risk, 55.6% intermediate risk and 16.7% high-risk. The complete remission rate was 94.4% after a median of 42 days. Both relapse rates and death rates were one patient (5.5%) each. No deaths were observed during consolidation. After a median follow-up of 29 months, the overall survival rate was 89.1%. Efficacy and safety of the International Consortium on Acute Promyelocytic Leukemia protocol has been reproduced in acute promyelocytic leukemia patients from a developing country.