The shortage of blood donor dogs in veterinary emergencies can lead to blood transfusions between animals whose blood type has not been identified. The antibody profile serves as a warning sign for animals that require a second blood transfusion, which is only advisable from compatible donor dogs. This article focuses on the determination of anti-DEA 1 antibodies using the flow cytometry technique in dogs that have undergone a transfusion using DEA 1-positive blood, compared to results obtained from crossmatching. Blood from 18 DEA 1-positive donors ranked according to the chromatographic technique was used to transfuse thirty-three animals with unknown blood types and which demonstrated negative crossmatching to donors. On post-transfusion days 7, 14, 21 and 28, 45% and 27% of the animals tested positive for the anti-DEA 1 antibody, through crossmatching and flow cytometry, respectively. Detecting antibodies using the flow cytometric technique has high specificity and sensitivity, while crossmatching methods are highly sensitive but manifest low specificity. Following the blood transfusion, animals that did not present as positive through crossmatching or flow cytometry were considered different from all other DEA 1-positive blood groups.A escassez de cães doadores de sangue em situações de emergência na Medicina Veterinária pode levar à realização de transfusões de sangue entre animais que não tiveram seu tipo sanguíneo previamente determinado. O padrão de anticorpos serve como um sinal de alerta para animais que serão submetidos a uma segunda transfusão sanguínea, sendo esta recomendável somente se o sangue for proveniente de cães doadores compatíveis. Este artigo aborda a determinação de anticorpos anti-AEC 1 pela técnica de citometria de fluxo em cães que receberam uma transfusão utilizando sangue do grupo AEC 1 positivo, comparando-se os resultados com aqueles obtidos a partir de reação cruzada. Foi utilizado o sangue de 18 animais doadores do tipo AEC 1 positivo classificados por técnica cromatográfica, a fim de transfundir trinta e três animais com tipos sanguíneos desconhecidos e que demonstraram reação cruzada negativa aos doadores. Nos dias 7, 14, 21 e 28 pós-transfusão, 45% e 27% dos animais mostraramse positivos para os anticorpos anti-AEC 1, respectivamente, pela reação cruzada e através de citometria de fluxo. A pesquisa de anticorpos com o emprego da técnica de citometria de fluxo tem alta especificidade e sensibilidade, enquanto a reação cruzada, altamente sensível, tem baixa especificidade. Animais que não apresentaram positividade após a transfusão de sangue na reação cruzada e na citometria de fluxo foram considerados como pertencentes a grupos sanguíneos diferentes do AEC 1 positivo. Palavras-chave: Isoanticorpos. Anticorpos caninos. AEC 1. Transfusão sanguínea em cães.

Santos et al. carried out a study on the immunophenotypic profile and demographic characteristics of a population of individuals diagnosed as new cases of acute leukemia over a period of 5 years. The main findings of the study were higher incidence of acute myeloid leukemia in women and CD66c and CD7 as the most frequent aberrant markers in acute lymphoblastic leukemia and acute myeloid leukemia.

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The dog erythrocyte antigen 1 (DEA 1) is the most immunogenic blood group in dogs, and blood transfusions may trigger some undesirable effects in veterinary patients, which are directly associated with incompatible transfusions. The present study aimed to investigate the frequency of positive DEA 1 blood group in blood donor dogs from a blood bank in Salvador, Bahia, Brazil, and also to calculate the risk of managing incompatible blood in both first and second transfusion. A number of 203 dogs of different breeds, aged between 1 and 8 years, weighing 28 kg, with no degree of kinship and of both sexes in Salvador - BA, Brazil were evaluated to investigate the blood type DEA 1 frequency, by means of chromatography and flow cytometry tests for blood typing. The risk of incompatible blood transfusion in either a first or a second transfusion was also calculated. The frequency of the DEA 1 group ranged from 0% to 100% in various breeds, but with a mean positivity of 62.07% (126/203). And the lowest risk of an DEA 1 negative animal receiving DEA 1 positive blood within the group of animals evaluated was 0.92% at a first transfusion; and the risk of the same animal receiving incompatible blood for the DEA group 1 in the second transfusion was 0.008%. The highest risk of an DEA 1 negative animal receiving DEA 1 positive blood from these animals was 69.12%; and the risk of receiving incompatible blood for DEA 1 was 47.77%. In conclusion, the frequency of the DEA 1 group varied between the studied breeds and the risk of incompatible blood transfusions varies according to donor and recipiente breeds, but this can be overridden if blood typing tests are performed along with the cross-reaction test for compatibility.

Background: The inclusion of the CD38-targeting antibody daratumumab (Dara) increases the depth and duration of the response, as demonstrated by Dara-VTd and Dara-VRd protocols to treat NDMM - TE patients (pts). However, the access to new drugs is a challenge for some countries in Latin America. There are many induction protocols and one of the most used inductions worldwide is cyclophosphamide (C), thalidomide (T) and dexamethasone (d)- (CTd). We hypothesized that the combination of daratumumab and CTd (Dara-CTd) could be safe and allow deeper activity in NDMM TE pts. Objective: The primary endpoint was the attainment of VGPR after two consolidation cycles post-autologous stem cell transplantation (ASCT). Secondary endpoints were the overall response rate during all treatment phases and minimal residual disease (MRD), based on the International Myeloma Working Group (IMWG) criteria that includes the next-generation flow by the EuroFlow® and PET-CT and the safety profile. An exploratory endpoint was the analysis of the immunologic change in the lymphocyte profile during the treatment. Methods: This is a phase II, open-label single-center clinical trial. The main inclusion criteria were: NDMM TE, creatinine clearance > 30 ml/min, normal cardiac, renal and liver function and the Easter Cooperative Oncology Group (ECOG) performance status = 0 - 2. The protocol scheme was Dara-CTd for up to four 28-day induction cycles: C-500mg oral (PO) on days 1,8 and 15, T at 100-200mg PO on days 1 to 28, Dex at 40mg PO on days 1,8,15 and 22 and Dara at 16mg/Kg/dose intravenous (IV) on days 1,8,15 and 22 during cycles 1 - 2 and every other week in cycles 3 - 4, followed by ASCT. Consolidation was started at D+30 after transplant and all patients received up to four 28-day consolidation cycles: Dara at 16mg/Kg and (d) at 40mg every other week, associated with T at 100mg PO on days 1 - 28. Dara at 16mg/Kg was used monthly as maintenance until progression or limiting toxicity. All patients received antiviral, anti-pneumocystis and anti-thrombotic prophylaxis. Results: The first patient was enrolled in November 2018. A total of 21 pts were included, the median age being 56 (range 38 - 67 years), 18 (85%) were non-white, 3 (14%) had an R-ISS = 1, 12 (57%) had an R-ISS = 2 and 3 (14%), an R-ISS = 3. Five (24%) pts had high-risk chromosomal abnormalities [del17p, t(4;14) or t(14;16)]. To date, 18 pts have completed induction, 12 have received transplants and 10 have completed D+90 post-transplant assessment. In an intention to treatment analysis, after the end of induction (cycle 4), 17 (95%) of the pts obtained > PR and 7 (33%) obtained VGPR or better. Ten patients have completed two consolidation cycles after transplant and 100% obtained > VGPR as best response, 8 (80%) obtained MRD = -10-5 negative remission by flow cytometry and 6 (60%) had negative PET-CTs. Five (50%) patients had both flow and PET-CT negativity. Two patients died from infection, one post-transplant, considered not related to the investigational agent, and another after consolidation, related to the investigational agent. The most common non-hematological adverse events (AEs) grades 3 and 4 before ASCT were neuropathy (n = 6), infusion reaction (n = 6), infection (n = 2), hypertension (n = 1) and rash (n = 1). Conclusion: This is the first study that combined daratumumab with CTd as induction for NDMM TE patients. This preliminary data has shown that the association of Dara-CTd achieved a deep response with a safety profile. Clinical trial information: NCT03792620. Disclosures De Queiroz Crusoe: Janssen: Research Funding.

Background: Newly drugs access for MM treatment still a challenge in some countries. One of the most available inductions for TE NDMM patients (pts) worldwide is cyclophosphamide (C), thalidomide (T) and dexamethasone (d)-(CTd). Dara the first anti- CD38, had been combined with VCd, VTd and VRd and markedly increased the depth and duration of the response. We hypothesized that Dara and CTd combination could be safe and allow deeper activity as an alternative protocol. Aims: The aims of this analysis were to evaluate Progression Free Survival (PFS) of Dara-CTd treatment and minimal residual disease (MRD) after one year of Dara maintenance. Primary endpoint of the study was to evaluate the VGPR after two consolidation cycles post-autologous stem cell transplantation (ASCT). Methods: This is a phase II, open-label single-center clinical trial. The main inclusion criteria were: TE NDMM, creatinine clearance > 30 ml/min, normal cardiac, renal and liver function and the Easter Cooperative Oncology Group (ECOG) performance status = 0 - 2. The protocol was Dara-CTd for up to four 28-day induction cycles: C-500mg oral (PO) on days 1,8 and 15, T at 100-200mg PO on days 1 to 28, (d) at 40mg PO on days 1,8,15 and 22 and Dara at 16mg/Kg/dose intravenous (IV) on days 1,8,15 and 22 during cycles 1 - 2 and every other week in cycles 3 - 4, followed by ASCT. All pts received up to four 28-day consolidation cycles that was started at D+30 after ASCT: Dara at 16mg/Kg and (d) at 40mg every other week, associated with T at 100mg PO on days 1 - 28. Dara at 16mg/Kg was used monthly as maintenance until progression or limiting toxicity. G-CSF was used for stem cell (SC) mobilization and plerixafor had been allowed whenever the pts need. The MRD was evaluated by next-generation flow (NGF) based and PET-CT was performed when the patient obtained NGF negativity or finished consolidation. PFS outcome was estimated using Kaplan-Meier method. All pts received antiviral, anti-pneumocystis and anti-thrombotic prophylaxis. Data cut-off was June 15, 2021. Results: The first pts was enrolled in November 2018. A total of 24 pts were included, the median age being 60 (range 37- 67 years), 23 (92%) were non-white, 5 (21%) had an R-ISS = 1, 12 (54%) had an R-ISS = 2 and 4 (16%), an R-ISS = 3. Six (25%) pts had high-risk chromosomal abnormalities [del17p, t(4;14) or t(14;16)]. To date, all pts have completed induction, 20 have received transplant and 17 have completed D+90 post-transplant assessment. No SC mobilization failure was observed, and six (30%) pts needed plerixafor use. By ITT analysis after a median follow up of 20 months the PFS at 12 and 18 months was 86%. No PFS difference was observed between different subgroups. Regarding response rates, after the end of induction (cycle 4), 19 (90%) of the pts obtained > PR and 8 (38%) obtained >VGPR, including three MRD negativity by NGF. 17 pts have completed two consolidation cycles after transplant and 94% obtained > VGPR as best response, 13 (76%) obtained MRD negativity by NGF and 10 (58%) had negative PET-CT. Seven (41%) pts had both flow and PET-CT negativity. Six pts completed one year of maintenance and five of them (83%) still MRD negativity by NGF. Four pts died from infection, two of them related with covid infection (one before transplant and one during maintenance). Another case post-transplant, considered not related to the investigational agent and one after consolidation, related to the investigational agent. Two pts have discontinued treatment due to progression - 1 before ASCT e 1 during maintenance. The most common adverse events (AEs) grades 3 and 4 were neutropenia (n = 12), infusion reaction (n = 7), neuropathy (n = 6), lymphopenia (n = 4), infection (n = 3), hypertension (n = 1) and rash (n = 1). Summary/Conclusion: The Daratumumab - CTd protocol is an active regimen capable of producing deep and sustainable responses and improve the PFS of NDMM TE pts with a favorable safety profile. Clinical trial information: NCT03792620. Disclosures De Queiroz Crusoe: Janssen: Research Funding. Hungria: Sanofi: Honoraria, Other: Support for attending meetings/travel ; Takeda: Honoraria; Abbvie: Honoraria; Amgen, BMS, Celgene, Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings/travel .

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Background: CD38-targeting antibody Daratumumab (Dara) has been demonstrating significant improvement in (MM) patient's survival. Cyclophosphamide (C), thalidomide (T) and dexamethasone (D) - (CTd) is one of the most used induction protocols worldwide and the MAX-Dara study was the first that combine Dara-CTd as induction for (NDMM) (TE) patients. We hypothesized that this new combo + autologous stem cell transplantation (ASCT) could affect the quantitative recovery of distinct lymphocytes subsets. Objective: Primary endpoint was to quantify lymphocytes subpopulations in (NDMM) (TE) patients at different treatment phases. Secondary endpoint was to evaluate B cells subsets at same times. Methods: Peripheral blood of 10 NDMM TE patients was collected at three different moments: at diagnose, after 4 induction cycles and after two consolidation cycles post- (ASCT). Dara-CTd protocol was for up to four 28-day induction cycles: C-500mg per oral (PO) d 1,8 and 15, T at 100-200mg PO d 1 to 28, Dex at 40mg PO d 1,8,15 and 22 and Dara 16mg/Kg/dose IV on d 1,8,15 and 22 during cycles 1 - 2 and every other week in cycles 3 - 4, followed by ASCT. Consolidation was started at D+30 after ASCT and all patients received up to four 28-day consolidation cycles: Dara 16mg/Kg and (D) at 40mg every other week, associated with T at 100mg PO d 1 - 28. Dara 16mg/Kg was used monthly as maintenance until progression or limiting toxicity. Flow cytometry was used to detect lymphocyte surface by CD3, CD4, CD5, CD8, CD16, CD19, CD20, CD38, CD45 and CD56 in the scatter plot. B cells were isolated and subpopulations (naïve B cells, class and non-class switched memory B cells, , IgD-CD27- memory B cells and plasma blasts) were detected by CD20, CD24, CD27, CD38, CD45 and IgD. Statistical analysis was performed using the SPSS® v25.0. Results: The median number of lymphocytes subsets at diagnosis were 1139 x 10³/μL for T cells, 155 x 10³/μL for B cells and 284 x 10³/μL for NK cells. After four cycles of Dara-CTD the median number of T, B and NK cells had dropped to 834, 7.5 and 8.0 x 10³/μL respectively (p<0.05). After two consolidation cycles post-ASCT, the T cells showed full reconstitution (1246 x 10³/μL) while B cells and NK cells had weakly reconstitution (20 x 10³/μL and 33 x 10³/μL, respectively). Regarding B cells subpopulations, the median B cell naïve numbers decreased from 32 x 10³/μL to 1 x 10³/μL (after 4 cycles), and recovery post-ASCT to 14 x 10³/μL. Class and non-class switched memory B cells numbers decreased after induction from 30 to 3.5 x 10³/μL and 37 to 2.0 x 10³/μL respectively. These subpopulations recovery after ASCT+ two consolidation cycles were not observed. Discussion: Different cells populations expresses CD38 antigen in their surface and depending on that, transitional lymphocytes counts reduction have been shown with different protocols using Dara. The present study confirmed that there is a decrease on total lymphocytes numbers after Dara- use. After two consolidation cycles post-ASCT, T cells counts had been recovered, while NK and B cells had a slightly recovery suggesting that Dara-CTD combination had a slighted negative impact in those lymphocytes' reconstitution. Concerning specifically B cells populations, we found that naive B cell was the first to showed faster recovery, although it was still below the reference range (33 - 259 x 10³/μL). Conclusion: This is the first study that reported lymphocyte profile with Dara plus CTD protocol. The preliminary data suggests that Dara-CTD reduces all lymphocytes populations after induction phase, but after ASCT followed by two consolidations cycles full reconstitution of T cells and slight recovery of B and NK cells was observed. Disclosures De Queiroz Crusoe: Janssen: Research Funding.