Multiple myeloma and Chagas disease: qPCR as a marker for preemptive antiparasitic therapy: a case reports series and review

ABSTRACT Multiple myeloma (MM) associated with Chagas disease is rarely described. This disease and its therapy suppress T cell and macrophage functions and increase regulatory T cell function, allowing the increase of parasitemia and the risk of Chagas Disease Reactivation (CDR). We aimed to analyze the role of conventional (cPCR) and quantitative Polymerase Chain Reaction (qPCR) for prospective monitoring of T. cruzi parasitemia, searching for markers of preemptive antiparasitic therapy in MM patients with Chagas disease. Moreover, we investigated the incidence and management of hematological diseases and CDR both inside and outside the transplant setting in the MEDLINE database. We found 293 studies and included 31 of them. Around 1.9-2.0% of patients with Chagas disease were reported in patients undergoing Stem Cell Transplantation. One case of CDR was described in eight cases of MM and Chagas disease. We monitored nine MM and Chagas disease patients, seven under Autologous Stem Cell Transplantation (ASCT), during 44.56±32.10 months (mean±SD) using parasitological methods, cPCR, and qPCR. From these patients, three had parasitemia. In the first, up to 256 par Eq/mL were detected, starting from 28 months after ASCT. The second patient dropped out and died soon after the detection of 161.0 par Eq/mL. The third patient had a positive blood culture. Benznidazole induced fast negativity in two cases; followed by notably lower levels in one of them. Increased T. cruzi parasitemia was related to the severity of the underlying disease. We recommend parasitemia monitoring by qPCR for early introduction of preemptive antiparasitic therapy to avoid CDR.

Managing patients with multiple myeloma during the COVID-19 pandemic: recommendations from an expert panel - ABHH monoclonal gammopathies committe

ABSTRACT Since the World has been facing the COVID-19 pandemic, special attention has been taken concerning cancer patients; related to their immunosuppression status, adding risk for more aggressive COVID-19 and mortality, but also concerns about the access and the quality of care in cancer therapy. The COVID-19 pandemic impacts the number of infected, its related mortality, as well as the care of cancer patients. Multiple myeloma patients are a particular group with several important aspects to be considered during pandemic times. In essence, they are immunosuppressed in different intensities during their treatment. Most of them are elderly and all of them require long-term therapy, with prolonged contact with the health care system, possibly including a stem cell transplant during the treatment. A panel of experts in multiple myeloma and infectious diseases discusses pieces of evidence and the lack of the same in the scenario of COVID-19 in myeloma patients, while also exposing what is expected for the next phases of the COVID-19 pandemic.

Superiority of the triple combination of bortezomib, cyclophosphamide and dexamethasone versus cyclophosphamide, thalidomide and dexamethasone in patients with newly diagnosed multiple myeloma, eligible for transplantation

ABSTRACT Background: The treatment of multiple myeloma (MM) has evolved significantly in the past decade, and new drug combinations have improved the response rates and prolonged survival. Studies comparing different induction chemotherapy regimens have shown that triple combinations have better results than double combinations. However, comparisons among different triple combinations are rare in the literature. Methods: We retrospectively compared two triple combinations comprising bortezomib, cyclophosphamide and dexamethasone (VCD) versus thalidomide, cyclophosphamide and dexamethasone (CTD), and aimed at identifying which of the two combinations would yield better response rates following four induction cycles prior to hematopoietic cell transplantation in patients with untreated multiple myeloma. Results: We retrospectively reviewed the medical records of 311 patients from 24 different centers.The VCD regimen was used as induction therapy by 117 (37.6%) patients, whereas 194 (62.4%) patients received the CTD regimen. After four cycles of induction on an intention-to-treat basis, 54% of the patients in the VCD group achieved at least very good partial response versus 42.8% in the CTD group (p = 0.05). We observed no difference in neuropathy or thrombotic events rates among the two regimens. Conclusion: Our results corroborate the superiority of the triple combination regimes containing bortezomib over the triple combination with thalidomide as pre ASCT induction therapy in MM.

Is it feasible to use granulocyte-colony stimulating factor alone to mobilize progenitor cells in multiple myeloma patients induced with a cyclophosphamide, thalidomide and dexamethasone regimen?

ABSTRACT Background: Cyclophosphamide plus thalidomide as induction for multiple myeloma patients eligible for autologous stem cell transplantation may be a limiting factor for cell mobilization. The minimum acceptable mobilized peripheral blood stem cell count to prevent deleterious effects during transplantation is 2.0 × 106 CD34+ cells/kg. Combining other treatments to granulocyte-colony stimulating factor, such as cyclophosphamide, could overcome the mobilization limitation. The objective of this study was to assess the number of CD34+ cells mobilized using granulocyte-colony stimulating factor with and without cyclophosphamide after induction with cyclophosphamide, thalidomide and dexamethasone. Methods: A retrospective study was performed of a cohort of multiple myeloma patients submitted to autologous stem cell transplantations at two Brazilian centers between May 2009 and July 2013. The oral cyclophosphamide and thalidomide induction doses used were 1500 mg/month and 100-200 mg/day, respectively. Mobilization doses were 10-15 mcg/kg granulocyte-colony stimulating factor with 2-4 g/m2 cyclophosphamide, or 15-20 mcg/kg granulocyte-colony stimulating factor alone for 5 days. Collection of >2.0 × 106 CD34+ cells/kg was considered sufficient. Results: Eighty-eight patients were analyzed; only 18 received cyclophosphamide. The median age was 58 years old (range: 51-62) for the granulocyte-colony stimulating factor group and 56.5 years old (range: 54-60) for granulocyte-colony stimulating factor plus cyclophosphamide group. Fifty-two patients were male. Eighty cases (90.9%) were Durie-Salmon Staging System III-A/B and 38 (44.7%) and 20 cases (23.5%) were International Staging System 2 and 3, respectively. The group that received cyclophosphamide collected a higher median number of progenitor cells [3.8 (range: 3.1-4.4) vs. 3.2 (range: 2.3-3.8)] (p-value = 0.008). No correlation was observed between better responses or number of induction cycles and the number of cells collected. Conclusion: The number of cells mobilized with granulocyte-colony stimulating factor plus cyclophosphamide was higher. However, in both groups, the median number of CD34+ cells was sufficient to perform a single autologous stem cell transplantation; no deleterious effects were reported during harvesting.

Emulsión lipídica como antídoto al deterioro neurológico progresivo, tras la infiltración de altas dosis de anestésico local: a propósito de un caso / Lipid emulsion as an antidote to progressive neurological impairment after injection of high doses of local anesthetic: case report

La infiltración de anestésico local (AL) está cada vez más extendida como indicación en el tratamiento del dolor neuropático. La intoxicación por AL es poco frecuente pero grave, potencialmente mortal y de difícil manejo. Cursa con afectación del nivel de conciencia, crisis comiciales y bloqueos de la conducción cardiaca. La emulsión lipídica (EL) al 20 % es el único tratamiento específico descrito hasta la fecha y ha mejorado el pronóstico de estos casos. Presentamos el caso de un paciente con deterioro neurológico progresivo tras la infiltración de altas dosis de AL por un dolor neuropático refractario a otros tratamientos. El paciente fue tratado con emulsión lipídica al 20 % revirtiendo el cuadro neurológico de forma precoz y completa. La aparición de síntomas neurológicos progresivos en el contexto de una infiltración de anestésico local debe alertarnos sobre una posible intoxicación para iniciar tratamiento precoz con emulsión lipídica al 20 %, evitando un pronóstico infausto. Sin embargo, la prevención sigue siendo la herramienta principal.

The infiltration of local anesthetic (LA) is increasingly widespread as an indication in the treatment of neuropathic pain. AL poisoning is rare but serious, life-threatening entity and its management may be very difficult. It occurs with decreased level of consciousness, seizures and cardiac conduction blocks. The lipid emulsion (EL) 20% is the only specific treatment described to date and it has improved the prognosis of these patients. We report the case of a patient with progressive neurological deterioration after injection of high doses of LA for treat a neuropathic pain refractory to other treatments. The patient was treated with lipid emulsion 20% with reversing all the neurological symptoms early and completely. The occurrence of progressive neurological symptoms in the context of a local anesthetic infiltration, should alert us to a possible poisoning and to start early treatment with lipid emulsion 20%, to avoid poor prognosis. However, prevention remains the main tool.

α-Lactoalbúmina como ingrediente de fórmulas infantiles

La α-lactoalbúmina es la principal proteína del lactosuero en la leche materna, alcanzando una concentración de 2,44 g/L en la leche madura. Su principal función es la síntesis de lactosa a partir de glucosa y galactosa en la glándula mamaria, aunque posee además otros efectos beneficiosos sobre la salud del lactante debido a su elevada proporción de aminoácidos esenciales (triptófano y cisteína). Según diversos estudios parece influir positivamente en la absorción de hierro en el intestino del niño, y en experimentos in vitro, unida al ácido oleico (complejo HAMLET), es efectiva frente a tumores celulares como el papiloma humano. El complejo HAMLET también presenta un claro efecto antimicrobiano frente a Streptococcus pneumoniae, Haemophilus influenzae, cepas enteropatógenas de Escherichia coli y Salmonella thypimurium, sin embargo no se ha demostrado que durante la digestión de la leche materna se forme dicho complejo en el tracto digestivo del lactante. El desarrollo de fórmulas infantiles destinadas a la alimentación del niño durante el primer año de vida ha mejorado considerablemente en las últimas décadas intentando no sólo adecuar la concentración de nutrientes a los requerimientos del lactante, sino también adicionando compuestos bioactivos de diferente naturaleza, como la α-lactoalbúmina, con el objetivo de alcanzar los efectos funcionales que se producen en los niños alimentados con leche materna.

α-Lactalbumin as an ingredient of infant formula. α-lactalbumin is the main whey protein in human milk rising 2,44 g/L in mature milk. It has a key function in the synthesis of lactose from glucose and galactose in the mammary gland although this compound has also other beneficial effects on the infant health due to the high proportion of essential aminoacids (tryptophan and cysteine). It seems also to increase iron absorption in the digestive track, and in in vitro experiments, linked to oleic acid (HAMLET complex), has shown anticarcinogenic effects against cellular tumor such as human papilloma. In addition, this complex has been reported to exhibit antimicrobial properties against Streptococcus pneumoniae,Haemophilus influenzae, enteropathogenic strains of Escherichia coli and Salmonella thypimurium. However, the in vivo synthesis of HAMLET complex during milk digestion has not been proved yet. Infant formula have been improved considerably during the last decades not only adapting nutrient concentrations to infants requirements but also by the addition of new bioactive ingredients such as α-lactalbumin, to have the same functional effect as in breast fed babies.

Fatores prognósticos no Mieloma Múltiplo / Prognostic factors in Multiple Myeloma

Nos últimos dez anos, grandes mudanças ocorreram no tratamento do MM com a utilização de novas drogas. Frente a estas novas opções de tratamento é essencial reconhecermos parâmetros clínicos ou biológicos que orientem a melhor escolha terapêutica. Mais recentemente foi validado um novo e simples sistema de estadiamento, International Staging System (ISS), baseado nos valores dabeta2 microglobulina e albumina sérica. Os pacientes são classificados em três grupos de risco: Estádio I: beta2M <3,5 mg/dl e albumina > 3,5 g/dl. Mediana de sobrevida de 62 meses; Estádio II: beta2 M <3,5 mg/l e albumina <3,5g/dl ou beta2 > 3,5 - < 5,5 mg/l. Mediana de sobrevida 49 meses; Estádio III: beta2 > 5,5 mg/l. Mediana de sobrevida de 29 meses. Atualmente, a citogenética e achados moleculares estão sendo amplamente reconhecidos como fatores de prognóstico. A deleção do cromossomo 13/13q-, translocação t(4;14), deleção p53 e, mais recentemente, a amplificação da banda cromossômica 1q21 estão associadas a prognóstico reservado.

Over the last 10 years, great changes have occurred in the treatment of multiple myeloma (MM) due to the use of new drugs. Considering the new options, it is essential to recognize clinical and biological parameters to arrive at the best therapeutic choice. More recently the new International Staging System (ISS) for multiple myeloma was validated which utilizes two straight forward laboratory parameters: the beta2 microglobulin (beta2M) and albumin levels. Stage I: beta2M < 3.5 mg/L and albumin level > 3.5 g/dL with a median survival of 62 months; stage II: beta2M < 3.5 and albumin < 3.5 g/dL or beta2M > 3.5 to < 5.5 g/dL with a median survival of 49 months; stage III: > 5.5 g/dL with a median survival of 29 months. The importance of cytogenetics and molecular features as prognostic factors is being recognized. Deletion of chromosome 13 or 13q, the t(4:14) translocation, p53 deletion and amplification of chromosome band 1q21 are all associated with poor prognosis.

Estimación de la ingesta y necesidades de enriquecimiento de folatos y ácido fólico en alimentos / Folate and folic acid ontake estimation and food enrichment requirements

El término folato se utiliza de forma genérica para denominar las distintas formas químicas derivadas del ácido fólico, una de las vitaminas del grupo B (concretamente la vitamina B). Son esenciales en el metabolismo al actuar como cofactores en las reacciones de transferencia de un carbono. No obstante, solamente las plantas y los microorganismos son capaces de sintetizarlos de novo, de tal forma que tanto los animales como el hombre necesitan ingerirlos a tráves de los alimentos de la dieta. se encuentra ampliamente extendido en la naturaleza, presentándose en mayor cantidad en las verduras de hoja ancha, en hígado y en cereales Aún así, en la actualidad es una de las deficiencias nutricionales más comunes en todo el mundo, y tiene graves consecuencias sobre la salud humana. Existe evidencia de que incluso en países desarrollados la ingesta de folatos es generalmente baja, e incluso en algunos casos por debajo de los niveles óptimos. Las autoridades competentes de numerosos países están tomando medidas a este respecto, de tal forma que se está realizando la fortificación, de numerosos alimentos considerados de consumo diario, tales como leche o cereales, ya sea de forma obligatoria (Estados Unidos, Canadá o Chile) o voluntaria (la mayoría de los países de Europa)

Aspergillary bronchopneumonia: an unusual cause of atelectasis and asphyxia in a leukemic patient

Aspergilose pulmonar: causa infrequente de atelectasia e asfixia em paciente leucêmico. Paciente de 22 anos em primeira recidiva de leucemia linfóide aguda de tipo T desenvolveu febre e infiltrado pulmonar após 23 dias de granulocitopenia. Apesar do uso de Anfotericina B, houve progressäo da doença pulmonar com aparecimento de expectoraçäo purulenta, atelectasia do pulmäo direito e insuficiência ventilatória. Esta foi resolvida após eliminaçäo de rolha brônquica espessa. Culturas de escarro revelaram Candida Albicans e Staphylococcus epidermidis; a microscopia óptica da rolha revelou a presença de hifas de aspergilos. O paciente foi a óbito 9 dias após, por infecçäo disseminada por aspeergilos, confirmada por necrópsia

Leucemia mielóide aguda após tratamento da doença de Hodgkin / Acute mycloid leukemia after treatment of the Hodgkin's disease

O desenvolimento de leucemias agudas, principalmente a leucemia mielóide aguda constitui-se em uma complicaçäo grave em pacientes tratados com rádio e/ou quimioterapia para doença de Hodgkin e tem aumentado acentuadamente nos ultímos 15 anos. Säo descritos dois casos de leucemia mielóide aguda após rádio e quimioterapia para doença de Hodgkin que ocorreram em uma populaçäo de 87 pacientes tratados. Foram realizadas autópsias completas em ambos. Os pacientes tinham idade inferior a 30 anos, receberam terapêutica combinada por um período prolongado (mais de 12 meses) com intervalo entre o diagnóstico da doença de Hodgkin e o aparecimento da leucemia mielóide aguda maior que 44 meses e sobrevida menor que 12 meses. Näo se observou doença de Hodgkin residual nos dois casos