Impact of CD34 Cell Dose and Conditioning Regimen on Outcomes after Haploidentical Donor Hematopoietic Stem Cell Transplantation with Post-Transplantation Cyclophosphamide for Relapsed/Refractory Severe Aplastic Anemia.

Severe aplastic anemia (SAA) is a life-threatening disease that can be cured with allogeneic cell transplantation (HCT). Haploidentical donor transplantation with post-transplantation cyclophosphamide (haplo-PTCy) is an option for patients lacking an HLA-matched donor. We analyzed 87 patients who underwent haplo-PTCy between 2010 and 2019. The median patient age was 14 years (range, 1 to 69 years), most were heavily transfused, and all received previous immunosuppression (25% without antithymocyte globulin). Almost two-thirds (63%) received standard fludarabine (Flu)/cyclophosphamide (Cy) 29/total body irradiation (TBI) 200 cGy conditioning, and the remaining patients received an augmented conditioning: Flu/Cy29/TBI 300-400 (16%), Flu/Cy50/TBI 200 (10%), or Flu/Cy50/TBI 400 (10%). All patients received PTCy-based graft-versus-host disease (GVHD) prophylaxis. Most grafts (93%) were bone marrow (BM). The median duration of follow-up was 2 years and 2 months. The median time to neutrophil recovery was 17 days. Primary graft failure occurred in 15% of the patients, and secondary or poor graft function occurred in 5%. The incidences of grade II-IV acute GVHD was 14%, and that of chronic GVHD was 9%. Two-year overall survival and event-free survival (EFS) were 79% and 70%, respectively. EFS was higher for patients who received augmented Flu/Cy/TBI (hazard ratio [HR], .28; P = .02), and those who received higher BM CD34 cell doses (>3.2 × 10E6/kg) (HR, .29; P = .004). The presence of donor-specific antibodies before HSCT was associated with lower EFS (HR, 3.92; P = .01). Graft failure (HR, 7.20; P < .0001) was associated with an elevated risk of death. Cytomegalovirus reactivation was frequent (62%). Haploidentical HCT for SAA is a feasible procedure; outcomes are improved with augmented conditioning regimens and BM grafts with higher CD34 cell doses.

A Case Series of Post-Transplantation Cyclophosphamide in Unrelated Donor Hematopoietic Cell Transplantation for Aplastic Anemia.

Patients with severe aplastic anemia (SAA) who fail immunosuppressive therapy have a dismal prognosis. Hematopoietic stem cell transplantation (HSCT) from an unrelated donor (URD) is one of the most effective treatment options. Two institutions have independently adopted a post-transplantation cyclophosphamide (PTCy) approach for patients with SAA undergoing HSCT from a URD. Thirteen patients were included, 11 of whom had been treated with immunosuppressive therapy. Eight patients had a mismatched URD. All patients were conditioned with fludarabine, cyclophosphamide, and total body irradiation, in various dosage combinations. PTCy was given at a dose of 100 mg/kg. Two patients died, and overall survival was 85% at 2 years. All patients engrafted, but 1 patient developed secondary graft failure. Of the 11 patients alive after 2 years, 9 had complete donor chimerism. All surviving patients were transfusion-independent. Ten patients (77%) had cytomegalovirus reactivation, and 2 patients had more than 1 reactivation. No Epstein-Barr virus reactivation or post-transplantation lymphoproliferative disease was observed. Four patients had mild hemorrhagic cystitis. In summary, our findings show that PTCy is a promising treatment for patients with SAA undergoing URD HSCT.

Effect of antithymocyte globulin source on outcomes of bone marrow transplantation for severe aplastic anemia.

For treatment of severe aplastic anemia, immunosuppressive therapy with horse antithymocyte globulin results in superior response and survival compared with rabbit antithymocyte globulin. This relative benefit may be different in the setting of transplantation as rabbit antithymocyte globulin results in more profound immunosuppression. We analyzed 833 severe aplastic anemia transplants between 2008 and 2013 using human leukocyte antigen (HLA)-matched siblings (n=546) or unrelated donors (n=287) who received antithymocyte globulin as part of their conditioning regimen and bone marrow graft. There were no differences in hematopoietic recovery by type of antithymocyte globulin. Among recipients of HLA-matched sibling transplants, day 100 incidence of acute (17% versus 6%, P<0.001) and chronic (20% versus 9%, P<0.001) graft-versus-host disease were higher with horse compared to rabbit antithymocyte globulin. There were no differences in 3-year overall survival, 87% and 92%, P=0.76, respectively. Among recipients of unrelated donor transplants, acute graft-versus-host disease was also higher with horse compared to rabbit antithymocyte globulin (42% versus 23%, P<0.001) but not chronic graft-versus-host disease (38% versus 32%, P=0.35). Survival was lower with horse antithymocyte globulin after unrelated donor transplantation, 75% versus 83%, P=0.02. These data support the use of rabbit antithymocyte globulin for bone marrow transplant conditioning for severe aplastic anemia.

Infection with multidrug-resistant gram-negative bacteria in a pediatric oncology intensive care unit: risk factors and outcomes / Infecção por bactérias gram-negativas multirresistentes em uma unidade de terapia intensiva pediátrica oncológica: fatores de risco e resultados

ABSTRACT OBJECTIVE: This study aimed at evaluating the predictors and outcomes associated with multidrug-resistant gram-negative bacterial (MDR-GNB) infections in an oncology pediatric intensive care unit (PICU). METHODS: Data were collected relating to all episodes of GNB infection that occurred in a PICU between January of 2009 and December of 2012. GNB infections were divided into two groups for comparison: (1) infections attributed to MDR-GNB and (2) infections attributed to non-MDR-GNB. Variables of interest included age, gender, presence of solid tumor or hematologic disease, cancer status, central venous catheter use, previous Pseudomonas aeruginosa infection, healthcare-associated infection, neutropenia in the preceding 7 days, duration of neutropenia, length of hospital stay before ICU admission, length of ICU stay, and the use of any of the following in the previous 30 days: antimicrobial agents, corticosteroids, chemotherapy, or radiation therapy. Other variables included initial appropriate antimicrobial treatment, definitive inadequate antimicrobial treatment, duration of appropriate antibiotic use, time to initiate adequate antibiotic therapy, and the 7- and 30-day mortality. RESULTS: Multivariate logistic regression analyses showed significant relationships between MDR-GNB and hematologic diseases (odds ratio [OR] 5.262; 95% confidence interval [95% CI] 1.282-21.594; p = 0.021) and healthcare-associated infection (OR 18.360; 95% CI 1.778-189.560; p = 0.015). There were significant differences between MDR-GNB and non-MDR-GNB patients for the following variables: inadequate initial empirical antibiotic therapy, time to initiate adequate antibiotic treatment, and inappropriate antibiotic therapy. CONCLUSIONS: Hematologic malignancy and healthcare-associated infection were significantly associated with MDR-GNB infection in this sample of pediatric oncology patients.

RESUMO OBJETIVO: Este estudo visou a avaliar os preditores e resultados associados às infecções por bactérias gram-negativas multirresistentes (BGN-MR) em uma unidade de terapia intensiva pediátrica oncológica (UTIP). MÉTODOS: Foram coletados dados com relação a todos os episódios de infecção por BGN que ocorreram em uma UTIP entre janeiro de 2009 e dezembro de 2012. As infecções por BGN foram divididas em dois grupos para comparação: 1) infecções atribuídas a BGN-MR e 2) infecções atribuídas a BGN não multirresistente. As variáveis de interesse incluíram idade, sexo, presença de tumor sólido ou malignidade hematológica, câncer, uso de cateter venoso central, infecção anterior por Pseudomonas aeruginosa, infecção hospitalar, neutropenia nos sete dias anteriores, duração da neutropenia, tempo de internação antes da UTI, duração da internação na UTI e uso de quaisquer dos seguintes nos 30 dias anteriores: agentes antimicrobianos, corticosteroides, quimioterapia ou radioterapia. Outras variáveis incluíram: tratamento antimicrobiano inicial adequado, tratamento antimicrobiano definitivo inadequado, duração do uso de antibióticos adequados, tempo de início da terapia antibiótica adequada, mortalidade em sete dias e mortalidade em 30 dias. RESULTADOS: As análises de regressão logística multivariada mostraram relações significativas entre as BGN-MR e as doenças hematológicas (razão de chance (RC) 5,262; intervalo de confiança de 95% (IC de 95%) 1,282-21,594; p = 0,021) e infecções hospitalares (RC 18,360; IC de 95% 1,778-189,560; p = 0,015). Houve diferenças significativas entre os pacientes com BGN-MR e BGN não MR com relação às seguintes variáveis: recebimento de terapia antibiótica empírica inicial inadequada, tempo para início do tratamento antibiótico adequado e recebimento de terapia antibiótica inadequada. CONCLUSÕES: A malignidade hematológica e a infecção hospitalar foram significativamente associadas à infecção por BGN-MR nessa amostra de pacientes pediátricos oncológicos.

Infection with multidrug-resistant gram-negative bacteria in a pediatric oncology intensive care unit: risk factors and outcomes.

OBJECTIVE: This study aimed at evaluating the predictors and outcomes associated with multidrug-resistant gram-negative bacterial (MDR-GNB) infections in an oncology pediatric intensive care unit (PICU). METHODS: Data were collected relating to all episodes of GNB infection that occurred in a PICU between January of 2009 and December of 2012. GNB infections were divided into two groups for comparison: (1) infections attributed to MDR-GNB and (2) infections attributed to non-MDR-GNB. Variables of interest included age, gender, presence of solid tumor or hematologic disease, cancer status, central venous catheter use, previous Pseudomonas aeruginosa infection, healthcare-associated infection, neutropenia in the preceding 7 days, duration of neutropenia, length of hospital stay before ICU admission, length of ICU stay, and the use of any of the following in the previous 30 days: antimicrobial agents, corticosteroids, chemotherapy, or radiation therapy. Other variables included initial appropriate antimicrobial treatment, definitive inadequate antimicrobial treatment, duration of appropriate antibiotic use, time to initiate adequate antibiotic therapy, and the 7- and 30-day mortality. RESULTS: Multivariate logistic regression analyses showed significant relationships between MDR-GNB and hematologic diseases (odds ratio [OR] 5.262; 95% confidence interval [95% CI] 1.282-21.594; p=0.021) and healthcare-associated infection (OR 18.360; 95% CI 1.778-189.560; p=0.015). There were significant differences between MDR-GNB and non-MDR-GNB patients for the following variables: inadequate initial empirical antibiotic therapy, time to initiate adequate antibiotic treatment, and inappropriate antibiotic therapy. CONCLUSIONS: Hematologic malignancy and healthcare-associated infection were significantly associated with MDR-GNB infection in this sample of pediatric oncology patients.

Predictors of 7- and 30-day mortality in pediatric intensive care unit patients with cancer and hematologic malignancy infected with Gram-negative bacteria

Background: Infection with Gram-negative bacteria is associated with increased morbidity and mortality. The aim of this study was to evaluate the predictors of 7- and 30-day mortality in pediatric patients in an intensive care unit with cancer and/or hematologic diseases and Gram-negative bacteria infection. Methods: Data were collected relating to all episodes of Gram-negative bacteria infection that occurred in a pediatric intensive care unit between January 2009 and December 2012, and these cases were divided into two groups: those who were deceased seven and 30 days after the date of a positive culture and those who survived the same time frames. Variables of interest included age, gender, presence of solid tumor or hematologic disease, cancer status, central venous catheter use, previous Pseudomonas aeruginosa infection, infection by multidrug resistant-Gram-negative bacteria, colonization by multidrug resistant-Gram- negative bacteria, neutropenia in the preceding seven days, neutropenia duration ≥3 days, healthcare-associated infection, length of stay before intensive care unit admission, length of intensive care unit stay >3 days, appropriate empirical antimicrobial treatment, definitive inadequate antimicrobial treatment, time to initiate adequate antibiotic therapy, appropriate antibiotic duration ≤3 days, and shock. In addition, use of antimicrobial agents, corticosteroids, chemotherapy, or radiation therapy in the previous 30 days was noted. Results: Multivariate logistic regression analysis resulted in significant relationship between shock and both 7-day mortality (odds ratio 12.397; 95% confidence interval 1.291–119.016 p = 0.029) and 30-day mortality (odds ratio 6.174; 95% confidence interval 1.760–21.664 p = 0.004), between antibiotic duration ≤3 days and 7-day mortality (odds ratio 21.328 95% confidence interval 2.834-160.536; p = 0.003), and between colonization by multidrug re...

Less graft-versus-host disease after rabbit antithymocyte globulin conditioning in unrelated bone marrow transplantation for leukemia and myelodysplasia: comparison with matched related bone marrow transplantation.

One of the major drawbacks for unrelated donor (UD) bone marrow transplantation (BMT) is graft-versus-host disease (GVHD). Despite results from randomized trials, antithymocyte globulin (ATG) is not routinely included for GVHD prophylaxis in UD BMT by many centers. One of ways to demonstrate the usefulness of rabbit ATG in UD BMT is to evaluate how its results approximate to those observed in matched related (MRD) BMT. Therefore, we compared the outcomes between UD BMT with rabbit ATG (Thymoglobulin) for GVHD prophylaxis (n = 25) and MRD BMT (n = 91) for leukemia and myelodysplasia. All but one patient received a myeloablative conditioning regimen. Grades II-IV acute GVHD were similar (39.5% vs. 36%, p = 0.83); however, MRD BMT recipients developed more moderate-severe chronic GVHD (36.5% vs. 8.6%, p = 0.01) and GVHD-related deaths (32.5% vs. 5.6%, p = 0.04). UD BMT independently protected against chronic GVHD (hazard ratio 0.23, p = 0.04). The 6-month transplant-related mortality, 1-year relapse incidence, and 5-year survival rates were similar between patients with non-advanced disease in the MRD and UD BMT groups, 13.8% vs. 16.6% (p = 0.50), 20.8% vs. 16.6% (p = 0.37), and 57% vs. 50% (p = 0.67), respectively. Stable full donor chimerism was equally achieved (71.3% vs. 71.4%, p = 1). Incorporation of rabbit ATG in UD BMT promotes less GVHD, without jeopardizing chimerism evolution, and may attain similar survival outcomes as MRD BMT for leukemia and myelodysplasia especially in patients without advanced disease.

Predictors of 7- and 30-day mortality in pediatric intensive care unit patients with cancer and hematologic malignancy infected with Gram-negative bacteria.

BACKGROUND: Infection with Gram-negative bacteria is associated with increased morbidity and mortality. The aim of this study was to evaluate the predictors of 7- and 30-day mortality in pediatric patients in an intensive care unit with cancer and/or hematologic diseases and Gram-negative bacteria infection. METHODS: Data were collected relating to all episodes of Gram-negative bacteria infection that occurred in a pediatric intensive care unit between January 2009 and December 2012, and these cases were divided into two groups: those who were deceased seven and 30 days after the date of a positive culture and those who survived the same time frames. Variables of interest included age, gender, presence of solid tumor or hematologic disease, cancer status, central venous catheter use, previous Pseudomonas aeruginosa infection, infection by multidrug resistant-Gram-negative bacteria, colonization by multidrug resistant-Gram-negative bacteria, neutropenia in the preceding seven days, neutropenia duration ≥3 days, healthcare-associated infection, length of stay before intensive care unit admission, length of intensive care unit stay >3 days, appropriate empirical antimicrobial treatment, definitive inadequate antimicrobial treatment, time to initiate adequate antibiotic therapy, appropriate antibiotic duration ≤3 days, and shock. In addition, use of antimicrobial agents, corticosteroids, chemotherapy, or radiation therapy in the previous 30 days was noted. RESULTS: Multivariate logistic regression analysis resulted in significant relationship between shock and both 7-day mortality (odds ratio 12.397; 95% confidence interval 1.291-119.016; p=0.029) and 30-day mortality (odds ratio 6.174; 95% confidence interval 1.760-21.664; p=0.004), between antibiotic duration ≤3 days and 7-day mortality (odds ratio 21.328; 95% confidence interval 2.834-160.536; p=0.003), and between colonization by multidrug resistant-Gram-negative bacteria and 30-day mortality (odds ratio 12.002; 95% confidence interval 1.578-91.286; p=0.016). CONCLUSIONS: Shock was a predictor of 7- and 30-day mortality, and colonization by multidrug resistant-Gram-negative bacteria was an important risk factor for 30-day mortality.

Different outcomes between cyclophosphamide plus horse or rabbit antithymocyte globulin for HLA-identical sibling bone marrow transplant in severe aplastic anemia.

The standard regimen for HLA-identical sibling bone marrow transplant (BMT) in severe aplastic anemia (SAA) is cyclophosphamide (Cy) and horse antithymocyte globulin (ATG). Horse ATG has been replaced by rabbit ATG in many countries due to the unavailability of the former product. This study was designed to assess if these ATG preparations are interchangeable in the preparative regimen for matched related BMT in SAA. Forty consecutive BMTs were retrospectively analyzed: 20 received Cy plus horse ATG and 20 received Cy plus rabbit ATG as the preparative regimen. Conditioning with rabbit ATG was protective against acute graft-versus-host disease (aGVHD) grades II-IV and moderate-severe chronic GVHD (cGVHD), with incidence rates of 0% versus 35.2% (P = .009) and 0% versus 34.0% (P = .04), respectively. On day +100, the probability of proven/probable invasive fungal disease (IFD) was higher in patients conditioned with rabbit ATG, 31.2% versus 5.5%, respectively (P = .04). Earlier cytomegalovirus (CMV) reactivation (40 versus 50 days; P = .02) was observed with rabbit ATG. An inferior lymphocyte count on days +30 (0.360 versus 0.814 × 10(9)/L; P = .01) and +90 (0.744 versus 1.330 × 10(9)/L; P = .006) was noticed in recipients of rabbit ATG. The incidence of stable mixed chimerism was higher in recipients of rabbit ATG (18.2% versus 80%, respectively; P = .004). These results suggest that horse and rabbit ATG preparations have different biological and clinical properties and should not be used interchangeably in the preparative regimen for related BMT in SAA.

Leucemia mieloide aguda: atualidade brasileira de diagnóstico e tratamento / Acute myeloid leukemia: update in diagnosis and treatment in Brazil

Objective: To identify how the Brazilian hematology centers treated and diagnosed cases of acute myeloid leukemia in 2009. Methods: An epidemiological observational multicenter study of 11 listed Brazilian centers that treat acute myeloid leukemia and perform bone marrow transplantation. Data were collected from clinical charts of patients with acute myeloid leukemia treated at the said centers between 2005 and 2009. The availability for immunophenotyping and cytogenetic tests was assessed. Results:During 2009, a total of 345 new cases of acute myeloid leukemia were diagnosed. Differences were noted in the tests performed between patients who initiated treatment at the center and those referred for treatment. Of the participating centers, 72% conducted some type of molecular study in acute myeloid leukemia upon diagnosis. Conclusion: Treatment for acute myeloid leukemia in Brazil shows significantly inferior results when compared to other centers worldwide.

Objetivo: Identificar como centros de hematologia brasileiros trataram e diagnosticaram os casos de leucemia mieloide aguda no ano de 2009. Métodos: Estudo epidemiológico, observacional, multicêntrico de 11 centros brasileiros cadastrados para tratamento de leucemia mieloide aguda e transplante de medula óssea. Os dados foram coletados a partir de prontuários de pacientes com leucemia mieloide aguda tratados nos centros citados entre os anos de 2005 e 2009. Foi avaliada a disponibilidade para realização de exames de imunofenotipagem e citogenética nos centros estudados. Resultados: Foram diagnosticados 345 casos novos de leucemia mieloide aguda no ano de 2009. Observaram-se diferenças na realização de exames entre pacientes que iniciaram o tratamento no centro em relação àqueles referenciados para tratamento. Dos centros participantes, 72% realizaram algum tipo de pesquisa molecular em leucemia mieloide aguda ao diagnóstico. Conclusão: O tratamento da leucemia mieloide aguda no Brasil apresenta resultados muito inferiores quando comparado a outros centros mundiais.

Acute myeloid leukemia: update in diagnosis and treatment in Brazil.

OBJECTIVE: To identify how the Brazilian hematology centers treated and diagnosed cases of acute myeloid leukemia in 2009. METHODS: An epidemiological observational multicenter study of 11 listed Brazilian centers that treat acute myeloid leukemia and perform bone marrow transplantation. Data were collected from clinical charts of patients with acute myeloid leukemia treated at the said centers between 2005 and 2009. The availability for immunophenotyping and cytogenetic tests was assessed. RESULTS: During 2009, a total of 345 new cases of acute myeloid leukemia were diagnosed. Differences were noted in the tests performed between patients who initiated treatment at the center and those referred for treatment. Of the participating centers, 72% conducted some type of molecular study in acute myeloid leukemia upon diagnosis. CONCLUSION: Treatment for acute myeloid leukemia in Brazil shows significantly inferior results when compared to other centers worldwide.

Comparison between horse and rabbit antithymocyte globulin as first-line treatment for patients with severe aplastic anemia: a single-center retrospective study.

The best antithymocyte globulin preparation for first-line immune suppression in patients with severe aplastic anemia is still not clear. The aim of this study was to compare hematological response and overall survival in patients submitted to horse or rabbit antithymocyte globulin as first-line treatment for severe aplastic anemia. We retrospectively compared 71 consecutive patients with severe aplastic anemia, classified according to the antithymocyte globulin preparation. Analyses included variables related to patients and to immune suppression. Forty two patients (59.1%) received horse and 29 (40.9%) rabbit antithymocyte globulin. Response rates were higher at 6 months in patients submitted to horse in comparison to rabbit antithymocyte globulin (59.5% versus 34.5% respectively, p = 0.05). Median time to response was similar between the two groups (99 versus 88.5 days, respectively, for horse and rabbit antithymocyte globulin; p = 0.98). Overall survival at 2 years was significantly higher in patients submitted to horse in comparison to rabbit antithymocyte globulin (78.4% versus 55.4%, p = 0.03). Post-treatment response was strongly associated with survival at 2 years (97% in responders versus 41.2% in non-responders, p < 0.001). Use of rabbit antithymocyte globulin was an independent predictor of death (odds ratio 2.5; 95% confidence interval 1.03-6.04; p = 0.04). Rabbit antithymocyte globulin was associated with a significant and prolonged lymphopenia in comparison with horse antithymocyte globulin. Our data suggest the superiority of horse over rabbit antithymocyte globulin as first-line treatment for severe aplastic anemia, both regarding hematological response and survival.

High CD8+ lymphocyte dose in the autograft predicts early absolute lymphocyte count recovery after peripheral hematopoietic stem cell transplantation.

Early lymphocyte recovery (ELR) after autologous peripheral hematopoietic stem cell transplantation (ASCT) is an independent predictor for survival in patients with hematological and non-hematological cancers. Sixty-five ASCT for hematological cancers were retrospectively analyzed to identify the factors associated with ELR and to assess the impact of different mobilization regimens on the pre-collection absolute lymphocyte count (ALC). The CD8+ lymphocyte dose in the autograft and the pre-mobilization ALC were independently associated with ELR (P < 0.001 and P = 0.008, respectively). CD8+ lymphocyte doses higher than 0.1 x 10(9)/kg were strongly associated with ELR [P < 0.001, odds ratio 25.22, 95% confidence interval (CI) 4.98-127.69] and this cutoff may be used to predict ELR (P = 0.001, area under the curve 0.75, 95% CI 0.62-0.88). Mobilization with granulocyte colony-stimulating factor (G-CSF) alone, the pre-collection ALC and the number of apheresis sessions were independently associated with the CD8+ lymphocyte dose (P = 0.04, P = 0.001, and P < 0.001, respectively). The number of aphereses was the variable with the strongest correlation to the CD8+ lymphocyte dose (r(s) = 0.68, P < 0.001). Median pre-mobilization ALC was higher than pre-collection ALC in the subgroup of patients without ELR mobilized with chemotherapy followed by G-CSF (1090 vs. 758 lymphocytes/microL; P < 0.001). This reduction was not significant in the subgroup with ELR mobilized with chemotherapy plus G-CSF (1920 vs. 1539/microL, respectively; P = 0.23). These results suggest that the CD8+ lymphocyte dose in the autograft is critical for ELR after ASCT and also demonstrates that mobilization with chemotherapy followed by G-CSF significantly decreases the pre-collection ALC, especially in patients with low pre-mobilization ALC.

Identificação das variáveis relacionadas à recuperação precoce da contagem absoluta de linfócitos após o transplante autólogo de células-tronco hematopoiéticas de sangue periférico

A recuperação precoce da contagem absoluta de linfócitos (CAL) após o transplante autólogo de células-tronco hematopoiéticas (TACTH) é um preditor independente de melhores taxas de sobrevida em pacientes com câncer hematológico e não-hematológico. Realizou-se, neste estudo, uma análise retrospectiva de setenta e sete TACTH de sangue periférico em pacientes portadores de câncer hematológico objetivando identificar as variáveis associadas à recuperação precoce da CAL após o TACTH e avaliar o impacto de diferentes regimes de mobilização sobre a CAL pré-aférese. A dose de linfócitos CD8+ no enxerto autólogo e a CAL pré-aférese associaram-se independentemente à recuperação linfocitária precoce (P<0,001 e P=0,005; respectivamente). Uma dose de linfócitos CD8+ maior do que 0,1 x 109/kg associou-se fortemente à recuperação precoce da CAL (odds ratio 30,66; P<0,001; intervalo de confiança (IC) 95% 6,18-152,10), sendo este o melhor ponto de corte para predizer a recuperação linfocitária precoce (área sob a curva 0,77; P<0,001; IC 95% 0,64-0,89). A mobilização com o fator estimulador de colônias de granulócitos (G-CSF) isoladamente, a CAL pré-aférese e o número de sessões de aférese associaram-se independentemente com a dose de linfócitos CD8+ no enxerto autólogo (P=0,02, P<0,001 e P<0,001; respectivamente). O número de sessões de aférese foi a variável mais correlacionada com a dose de linfócitos CD8+ (rs=0,62, P<0,001). A comparação entre os valores medianos da CAL pré-mobilização e pré-aférese evidenciou uma redução de 1130 para 709 linfócitos/µL no subgrupo de pacientes sem recuperação linfocitária precoce e mobilizado com quimioterapia + G-CSF (P<0,001). Esta redução não foi significativa no subgrupo de pacientes com recuperação linfocitária precoce e mobilizado com quimioterapia + G-CSF (1905 versus 1500/µL, respectivamente; P=0,13). Estes resultados sugerem que a dose de linfócitos CD8+ no enxerto autólogo desempenha um papel crítico na recuperação precoce da CAL após o TACTH e demonstram que a mobilização com quimioterapia + G-CSF reduz significativamente a CAL pré-aférese, especialmente em pacientes com um baixo número de linfócitos no momento da mobilização.

Early lymphocyte recovery (ELR) after autologous peripheral hematopoietic stem cell transplantation (ASCT) is an independent predictor for survival in patients with hematological and non-hematological cancers. Seventy-seven ASCT for hematological cancers were retrospectively analyzed to identify the factors associated with ELR and to assess the impact of different mobilization regimens on the pre-collection absolute lymphocyte count (ALC). The CD8+ lymphocyte dose in the autograft and the precollection ALC were independently associated with ELR (P<0.001 and P=0.005; respectively). CD8+ lymphocyte doses higher than 0.1 x 109/kg were strongly associated with ELR (P<0.001, odds ratio 30.66, 95% confidence interval (CI) 6.18-152.10) and this cutoff may be used to predict ELR (P<0.001, area under the curve 0.77, 95% CI 0.64- 0.89). Mobilization with granulocyte colony-stimulating factor (G-CSF) alone, the precollection ALC and the number of apheresis sessions were independently associated with the CD8+ lymphocyte dose (P=0.02, P<0.001 and P<0.001; respectively). The number of aphereses was the variable with the strongest correlation to the CD8+ lymphocyte dose (rs=0.62, P<0.001). Median pre-mobilization ALC was higher than pre-collection ALC in the subgroup of patients without ELR mobilized with chemotherapy followed by G-CSF (1130 versus 709 lymphocytes/μL; P<0.001). This reduction was not significant in the subgroup with ELR mobilized with chemotherapy plus G-CSF (1905 versus 1500/μL, respectively; P=0.13). These results suggest that the CD8+ lymphocyte dose in the autograft is critical for ELR after ASCT and also demonstrates that mobilization with chemotherapy followed by G-CSF significantly decreases the pre-collection ALC, especially in patients with low pre-mobilization ALC.