Intermediate-dose cytarabine plus G-CSF as mobilization regimen for newly diagnosed multiple myeloma and heavily pre-treated patients with hematological and non-hematological malignancies.

BACKGROUND: Intermediate-dose cytarabine plus G-CSF has recently emerged as safe and effective mobilization regimen for heavily pre-treated patients with lymphoid malignancies. We prospectively tested this regimen in patients referred to our center in order to collect enough stem cells for hematopoietic rescue in autologous transplantation (auto-HSCT). STUDY DESIGN AND METHODS: cytarabine (1.6 g/m2) plus G-CSF (outpatient administration) was performed in 81 consecutive patients who underwent auto-HSCT. For analyses purposes patients were divided into Group A, consisted of 48 patients with newly diagnosed multiple myeloma (MM) and Group B with 33 heavily pre-treated patients (13 Hodgkin´s lymphoma, 7 non-Hodgkin´s lymphoma, 7 MM, 4 germ cell tumor, 2 non-promyelocytic acute myeloid leukemia). RESULTS: In the Group A, circulating CD34+ cells/µL was significantly higher, 90% started stem cell harvest on day 14, 98% collected ≥5.0 × 106 CD34+cells/kg and a single apheresis was sufficient in 92% of the cases. In the Group B, 85% started leukapheresis on day 14, 88% collected ≥2.0 × 106 CD34+cells/kg which was achieved with a single apheresis in 82% of the cases; a higher proportion of the patients (63.6% versus 33.3%) required platelet transfusions. Both groups exhibited few adverse events and the time to neutrophil and platelet recovery was similar between groups. CONCLUSION: Intermediate-dose cytarabine plus G-CSF mobilization is effective even for heavily pre-treated patients. The outpatient administration of G-CSF, the reliable prediction of the day to begin harvesting, the optimal CD34+ cell yield obtained with a single apheresis and the fewer occurrences of adverse events denoted the benefits of this regimen.

Evaluation of cytokine profile in the different phases of the autologous hematopoietic stem cell transplantation in patients with multiple myeloma.

BACKGROUND: The autologous hematopoietic stem cell transplantation (ASCT) is of fundamental importance in the treatment of patients with multiple myeloma (MM). Nevertheless, due to its toxicity, it decreases the number of bone marrow cells available, altering the cell interactions and causing an imbalance between pro- and anti-inflammatory cytokines. METHODS: Thus, we determined the serum levels of pro- and anti-inflammatory cytokines in samples of patients with MM obtained from the different phases of ASCT. RESULTS: In summary, the cytokines levels varied considering the different phases of ASCT. The levels of IL-1ra tend to increase in the post-apheresis period suggesting an anti-inflammatory role induced by the apheresis process. A response characterized by the increase in the concentrations of IL-5 and IL-8 was observed in the post-conditioning bone marrow aplasia phase. The rise in IL-5 levels was not correlated with any clinical or laboratory event in this framework; IL-8 was associated with positive blood cultures and seems to have an effect against microbial agents. The increase in the levels of IL-10 and IL-12 suggests a possible regulatory effect of the inflammatory response in the period of bone marrow recovery and IL-12 seems to be inversely associated with the presence of minimal residual disease. CONCLUSIONS: Apheresis process seems to induce an anti-inflammatory response, followed by a pro-inflammatory response and a stimulus for granulocytes differentiation.

Peripheral blood progenitor cell collection without close monitoring of peripheral blood CD34+ cells: A feasible strategy for multiple myeloma or pre-treated Non-Hodgkin's Lymphoma patients mobilized with low-dose cyclophosphamide plus G-CSF.

BACKGROUND: Daily monitoring of peripheral blood CD34+ cells may not be necessary for all patients with hematologic malignancies for adequate peripheral blood progenitor cells (PBPC) mobilization and harvesting. We therefore designed a regimen for PBPC mobilization in patients with multiple myeloma or pre-treated Non-Hodgkin's lymphoma based on a combination of low-dose cyclophosphamide (Cy) plus granulocyte colony-stimulating factor (G-CSF) without daily monitoring of peripheral blood CD34+ cells. STUDY DESIGN AND METHODS: A prospective study was performed on patients with multiple myeloma (n = 22) or pre-treated Non-Hodgkin's lymphoma (n = 17) whose PBPC were harvested according to the following regimen: 1.5 g/m(2) Cy at day 1, 12 microg/kg/day G-CSF from day +7 to +11 avoiding daily monitoring of peripheral blood CD34+ cells and two consecutive leukapheresis at days +12 and +13. The optimum threshold of 2x10(6) CD34+ cells per kg was established. RESULTS: The proportion of patients with higher CD34+ cell yield after two leukapheresis was similar: multiple myeloma (16/22-72.7%) and Non-Hodgkin's lymphoma (12/17-70.6%). Exposure to radiotherapy and greater than two prior chemotherapy regimens were significantly associated with lower yield in multiple myeloma (p = 0.002) and Non-Hodgkin's lymphoma patients (p = 0.002), respectively. CONCLUSION: Our data suggested that adequate yields of CD34+ cells may be achieved in multiple myeloma or pre-treated Non-Hodgkin's lymphoma mobilized with low-dose Cy plus G-CSF regardless of the daily monitoring of peripheral blood CD34+ cells.

Magnetic resonance tracking of magnetically labeled autologous bone marrow CD34+ cells transplanted into the spinal cord via lumbar puncture technique in patients with chronic spinal cord injury: CD34+ cells' migration into the injured site.

The purpose of this study was to demonstrate the possibility of delivering autologous bone marrow precursor cells into the spinal cord via lumbar puncture technique (LP) in patients with spinal cord injury (SCI). Magnetic resonance imaging provides a noninvasive method for studying the fate of transplanted cells in vivo. Considering these propositions, we studied magnetic resonance tracking of autologous bone marrow CD34(+) cells labeled with magnetic nanoparticles delivered into the spinal cord via LP in patients with SCI. Sixteen patients with chronic SCI were enrolled and divided into two groups; one group got their own labeled-CD34(+) cells injected into the spinal cord via LP (n = 10); the others received an injection, but it contained magnetic beads without stem cells (controls, n = 6). CD34(+) cells were magnetically labeled with magnetic beads coated with a monoclonal antibody specific for the CD34 cell membrane antigen. Magnetic resonance images were obtained by a standard turbospin echo-T2 weighted sequences before and 20 and 35 days after post-transplantation. The median number of CD34(+) cells injected via LP was 0.7 x 10(6) (range 0.45 to 1.22 x 10(6)). Magnetically labeled CD34(+) cells were visible at the lesion site as hypointense signals in five patients of the labeled-CD34(+) group 20 and 35 days after transplantation; these signals were not visible in any patient of the control group. We suggested for the first time that autologous bone marrow CD34(+) cells labeled with magnetic nanoparticles delivered into the spinal cord via LP technique migrated into the injured site in patients with chronic SCI.

Low-level laser therapy at different energy densities (0.1-2.0 J/cm2) and its effects on the capacity of human long-term cryopreserved peripheral blood progenitor cells for the growth of colony-forming units.

OBJECTIVE: The aim of this research was to investigate the effects of low-level laser therapy (LLLT) at different energy densities (0.1-2.0 J/cm(2)) on the capacity of long-term cryopreserved peripheral blood progenitor cell (PBPC) for growth of colony-forming units (CFU) in vitro. BACKGROUND DATA: There are no data concerning the effects of LLLT on human cryopreserved PBPC. METHODS: Cryopreserved PBPC samples were thawed after 3 years in order to demonstrate the positive effect of LLLT and after 5 years in order to confirm the LLLT's proliferative effect. Cultures were plated in quadruplicate 35-mm-diameter Petri dishes in methylcellulose medium (2 x 10(5)/mL final concentration) and incubated for 14 days at 37 degrees C with 5% CO(2). A 685-nm diode laser with 25-mW optical power was used as the source of irradiation. Cultures were exposed to energy densities of 0.1, 0.5, 1.0, 1.5, and 2.0 J/cm(2) before incubation (10 irradiated and 10 controls at each energy density group). RESULTS: A higher number of CFU was observed at the dose of 1.0 J/cm(2) (control 21.3 +/- 8.5 x 10(5) cells, irradiated 40.1 +/- 10.5 x 10(5) cells, p < 0.001). No differences were observed in cultures exposed to doses of 0.1, 0.5, and 1.5 J/cm(2). A decreased number of CFU was demonstrated in samples exposed to the dose of 2.0 J/cm(2) (control 21.4 +/- 11.9 x 10(5) cells, p = 0.013). PBPC samples cryopreserved for 5 years were thawed for CFU assays and exposed to a single dose of 1.0 J/cm(2); once again the exposed group showed a higher number of CFU (control 8.8 +/- 7.8 x 10(5) cells, irradiated 18.1 +/- 13.1 x 10(5) cells, p = 0.026). CONCLUSION: Dependent upon the energy density, LLLT elevates (1.0 J/cm(2)) or decreases (2.0 J/cm(2)) the potential of long-term cryopreserved PBPC for growth of CFU in vitro.

High prevalence of morphological subtype FAB M1 in adults with de novo acute myeloid leukemia in São José dos Campos, São Paulo.

CONTEXT AND OBJECTIVE: Geographical variations have been described in acute myelogenous leukemia (AML). In Brazil, few studies have been published on this. The aim of this study was to demonstrate the high prevalence of French-American-British (FAB) M1 subtype in adults with de novo AML in São José dos Campos, State of São Paulo, Brazil. DESIGN AND SETTING: Retrospective analysis, at Hospital Pio XII in São José dos Campos, a public non-teaching institution. METHODS: Records from 39 consecutive adult patients with de novo AML referred to Hospital Pio XII between January 2002 and September 2004 were reviewed. Peripheral blood and blood marrow smears were reviewed blindly by five hematologists and classified according to FAB criteria. The rates of remission, relapse, mortality according treatment phase, survival and leukemia-free survival were calculated. RESULTS: The prevalence of each category as determined via a consensus among five observers was M0: 0%; M1: 43.6%; M2: 30.7%; M3: 12.8%; M4: 5.1%; M5: 2.6%: M6: 2.6%; and M7: 2.6%. The remission and the relapse rates were 82% and 41% respectively. The mortality rate was 69% (induction of remission: 7/39, 17.9%; post induction: 10/32, 31.2%; and relapse: 10/16, 62.5%). The survival rate was 30% and leukemia-free survival was 33%. CONCLUSIONS: The study demonstrated a high prevalence of FAB M1 subtype in adults with de novo AML in São José dos Campos. Our data suggest the occurrence of different regional prevalences of FAB AML categories in Brazil.

Trends in mortality of adult patients diagnosed with myeloid leukemia from 1994 to 2011 in southeastern Brazil.

OBJECTIVE: To evaluate trends in mortality among adults with myeloid leukemia in the Vale do Paraíba, State of São Paulo. METHODS: Data from the Brazilian National Health Service database DATASUS provided the number of deaths caused by myeloid leukemia and the number of inhabitants per year in the Regional Health Division XVII from 1994 to 2011. Registries were categorized according to gender into four age ranges (over 20 years, 20-49, 50-69 and over 70 years) for an estimation of the annual percent change for age-adjusted mortality rates. The percent changes were calculated using the Joinpoint regression analysis model. RESULTS: Overall, a significant decline per year was demonstrated for the entire sample (over 20 years) across the 18-year period studied (annual percent change: -5.59%; 95% CI: -8.5 to -2.5% for males; p-value<0.05 and -7.02%; 95% CI -11.2 to -2.8% for females; p-value<0.05) with no significant difference between genders. In an analysis using two Joinpoints, significant drops were observed from 1994 to 2001 (annual percent change: -21.22%; 95% confidence interval: -27.9 to -13.9%; p-value<0.05) and from 1994 to 2003 (annual percent change: -12.86%; 95% confidence interval -22.2 to -2.5%; p-value<0.05) for men and women, respectively. The declining trends were greatest for patients aged over 70 years with the age-adjusted mortality rates in younger groups declining non-significantly except for males aged 50-69 years old. CONCLUSION: Our data suggest a significant decline per year in age-adjusted mortality rates of adult patients diagnosed with myeloid leukemia from 1994 to 2011 in the Vale do Paraíba, State of São Paulo.

Prevalence of anemia in a sample of elderly southeastern Brazilians.

OBJECTIVE: To demonstrate the proportion of anemia and its association with demographic and clinical characteristics in a representative sample of elderly people from São José dos Campos, São Paulo. METHODS: Demographic data and blood samples were collected from 398 over 65-year-old male and female individuals. Anemia was defined as hemoglobin concentration <12g/dL in women and <13g/dL in men. Anemic and non-anemic groups were compared using the chi-squared test and a multiple logistic regression model. RESULTS: The prevalence of anemia was 18.6% (20.8% in men and 17.6% in women). The percentages of anemia rose significantly across the age groups >75-80, >85-90 and >90-95 years (p-value=0.0251). There were no significant differences in gender, ethnic background, place of residence, years of schooling, income, comorbidities and use of medications. According to gender, the mean hemoglobin concentration and mean corpuscular volume were 11.5g/dL (range: 8.4-11.9g/dL) and 90.7fL (range: 63.0-111.7fL) for women and 11.9g/dL (range: 8.6-12.8g/dL) and 92.1fL (range: 59.8-100.1fL) for men. The great majority of anemia cases were mild with less than 6% having hemoglobin concentrations below 10.9g/dL. Mean corpuscular volume was lower than 80fL in six cases (8%), between 80 and 100fL in 65 cases (88%) and higher than 100fL in three cases (4%). CONCLUSION: A total of 18.6% of elderly people from São José dos Campos had mild anemia with the majority being normocytic. The percentages of anemia rose as the age increased demonstrating an association between age and anemia.

Three-dimensional conformal radiotherapy in prostate cancer patients: rise in interleukin 6 (IL-6) but not IL-2, IL-4, IL-5, tumor necrosis factor-α, MIP-1-α, and LIF levels.

PURPOSE: To investigate the effect of radiotherapy (RT) on serum levels of interleukin-2 (IL-2), IL-4, IL-5, IL-6, tumor necrosis factor alpha (TNF-α), macrophage inflammatory protein-1-alpha (MIP-1-α) and leukemia inhibitory factor (LIF) in patients with prostate cancer. METHODS AND MATERIALS: Forty eight patients with prostate cancer received three-dimensional conformal blocking radiation therapy with a linear accelerator. IL-2, IL-4, IL-5, IL-6, TNF-α, MIP-1-α, and LIF levels were measured by the related immunoassay kit 1 day before the beginning of RT and during RT at days 15 and 30. RESULTS: The mean IL-2 values were elevated before and during the RT in contrast with those of IL-4, IL-5, IL-6, TNF-α, MIP-1-α, and LIF, which were within the normal range under the same conditions. Regarding markers IL-2, IL-4, IL-5, TNF-α, MIP-1-α, and LIF, comparisons among the three groups (before treatment and 15 and 30 days during RT) did not show significant differences. Although values were within the normal range, there was a significant rise in IL-6 levels at day 15 of RT (p = 0.0049) and a decline at day 30 to levels that were similar to those observed before RT. CONCLUSIONS: IL-6 appeared to peak after 15 days of RT before returning to pre-RT levels. In contrast, IL-2, IL-4, IL-5, TNF-α, MIP-1-α, and LIF levels were not sensitive to irradiation. The increased levels of IL-6 following RT without the concurrent elevation of other cytokines involved in the acute phase reaction did not suggest a classical inflammatory response to radiation exposure. Further studies should be designed to elucidate the role of IL-6 levels in patients with prostate cancer treated with RT.

Oncohematological diseases in the Vale do Paraíba, State of São Paulo: demographic aspects, prevalences and incidences.

BACKGROUND: Based on the necessity of detailed information that supports effective strategies to improve cancer outcomes in the different regions of Brazil, the aims of this study were to report demographic aspects and to calculate the prevalence and incidence rates of oncohematological diseases in the region of Vale do Paraíba. METHODS: This is a multicentric prospective study carried out from October 2009 to March 2010. A total of 500 over 19-year-old patients were enrolled. Data such as type of healthcare insurance, gender, age, ethnic classification, place of residence, schooling, income, body mass index, new cases and the period between the first symptoms and a definite diagnosis were collected. The prevalence and incidence rates were calculated according to an estimated number of 1,319,800 inhabitants. RESULTS: The prevalence and incidence rates per 100,000 inhabitants in the period of six months were, respectively: acute myeloid leukemia 1.5 and 0.7; acute lymphoblastic leukemia 0.5 and 0.1; chronic lymphocytic leukemia 2.4 and 0.4; chronic myeloid leukemia 6.2 and 0.8; Hodgkin's lymphoma 2.9 and 0.9; non-Hodgkin lymphoma 9.8 and 4.3; multiple myeloma 5.7 and 0.7; myelodysplastic syndromes 2.1 and 0.2 and myeloproliferative syndromes 5.1 and 0.3. CONCLUSION: Giving the paucity of data in this field of investigation, our data may be useful for comparisons with those of other regions of Brazil and will assist in the implementation of treatment programs of oncohematological diseases in this region.

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.

Trends in mortality of adult patients diagnosed with myeloid leukemia from 1994 to 2011 in southeastern Brazil

Objective: To evaluate trends in mortality among adults with myeloid leukemia in the Vale do Paraíba, State of São Paulo. Methods: Data from the Brazilian National Health Service database DATASUS provided the number of deaths caused by myeloid leukemia and the number of inhabitants per year in the Regional Health Division XVII from 1994 to 2011. Registries were categorized according to gender into four age ranges (over 20 years, 20-49, 50-69 and over 70 years) for an estimation of the annual percent change for age-adjusted mortality rates. The percent changes were calculated using the Joinpoint regression analysis model. Results: Overall, a significant decline per year was demonstrated for the entire sample (over 20 years) across the 18-year period studied (annual percent change: −5.59%; 95% CI: −8.5 to −2.5% for males; p-value < 0.05 and −7.02%; 95% CI −11.2 to −2.8% for females; p-value < 0.05) with no significant difference between genders. In an analysis using two Joinpoints, significant drops were observed from 1994 to 2001 (annual percent change: −21.22%; 95% confidence interval: −27.9 to −13.9%; p-value < 0.05) and from 1994 to 2003 (annual percent change: −12.86%; 95% confidence interval −22.2 to −2.5%; p-value < 0.05) for men and women, respectively. The declining trends were greatest for patients aged over 70 years with the age-adjusted mortality rates in younger groups declining non-significantly except for males aged 50-69 years old. Conclusion: Our data suggest a significant decline per year in age-adjusted mortality rates of adult patients diagnosed with myeloid leukemia from 1994 to 2011 in the Vale do Paraíba, State of São Paulo. .

Prevalence of anemia in a sample of elderly southeastern Brazilians

Objective: To demonstrate the proportion of anemia and its association with demographic and clinical characteristics in a representative sample of elderly people from São José dos Campos, São Paulo. Methods: Demographic data and blood samples were collected from 398 over 65-year-old male and female individuals. Anemia was defined as hemoglobin concentration <12 g/dL in women and <13 g/dL in men. Anemic and non-anemic groups were compared using the chi-squared test and a multiple logistic regression model. Results: The prevalence of anemia was 18.6% (20.8% in men and 17.6% in women). The per- centages of anemia rose significantly across the age groups >75-80, >85-90 and >90-95 years (p-value = 0.0251). There were no significant differences in gender, ethnic background, place of residence, years of schooling, income, comorbidities and use of medications. Accord- ing to gender, the mean hemoglobin concentration and mean corpuscular volume were 11.5 g/dL (range: 8.4-11.9 g/dL) and 90.7 fL (range: 63.0-111.7 fL) for women and 11.9 g/dL (range: 8.6-12.8 g/dL) and 92.1 fL (range: 59.8-100.1 fL) for men. The great majority of ane- mia cases were mild with less than 6% having hemoglobin concentrations below 10.9 g/dL. Mean corpuscular volume was lower than 80 fL in six cases (8%), between 80 and 100 fL in 65 cases (88%) and higher than 100 fL in three cases (4%). Conclusion: A total of 18.6% of elderly people from São José dos Campos had mild anemia with the majority being normocytic. The percentages of anemia rose as the age increased demonstrating an association between age and anemia. .

Transplante autólogo de células-tronco hematopoéticas no Vale do Paraíba-SP: aspectos demográficos, clínicos e curvas de sobrevida / Autologous stem cell transplant in Vale do Paraiba, State of São Paulo: demographics and clinical aspects and survival curves

Demonstrar as características demográficas clínicas e taxas de sobrevida geral (SG) de pacientes tratados com transplante de células-tronco hematopoéticas (TCTH) autólogo no Vale do Paraíba-SP. Métodos - Análise retrospectiva de 129 pacientes atendidos no Hospital Pio XII de São José dos Campos entre 2005 e 2011. Coletaram-se registros de prontuário clínico, viabilidade das células CD34+ descongeladas,número de células CD34+ reinfundidas, reações adversas ao dimetilsulfóxido (DMSO), tempo de recuperação de contagem de neutrófilos (>0.5x109/L) e plaquetas (>20x109/L) e antimicrobianos prescritos. A SG 5 anos após o TCTH autólogo foi estimada para pacientes com mieloma múltiplo (MM), linfoma Hodgkin (LH) e linfoma não Hodgkin (LNH). Resultados - Foram selecionados 129 pacientes (67 homense 62 mulheres). A mediana das idades foi de 51 anos (18-70), 63 pacientes apresentavam MM, 25 LH, 24 LNH, 9 tumor germinativo, 7 leucemia mielóide aguda e 1 leucemia linfoblástica aguda. A mediana do número de células CD34+ reinfundidas foi de 6,02x106/kg (2,23-15,7) com viabilidade celular após descongelamento de 79% (62-93). O tempo para recuperação foi de 12 dias (9-18) para neutrófilose 13 dias (10-21) para plaquetas. Três pacientes apresentaram reações adversas ao DMSO. Trinta e três pacientes (25,6%) receberam antifúngico em associação aos antibióticos de amplo espectro de ação. As taxas de SG foram 57,7% (IC 33,8-71,5), 76,8% (IC 52,5-89,7) e 69,2% (IC 46,9-83,6) para MM, LH e LNH respectivamente. Conclusões - As características apresentadas demonstram que o TCTH autólogo é factível nesta região e as taxas de SG observadas em pacientes com MM, LH e LNH comparam-se favoravelmente com a literatura disponível...

To demonstrate the demographic and clinical aspects as well as the overall survival (OS) rates of patients treated with autologous stem cell transplantation (ASCT) in Vale do Paraíba-SP. Methods - Retrospective analysis of 129 patients from Pio XII Hospital of São José dos Campos that received treatment between 2005 and 2011. Data from the pronctuaries of the patients, number of CD34+ cells reinfused, viability of defrosted CD34+ cells, reactions induced by dimethylsulfoxide (DMSO), time to recover neutrophils and platelets count and antimicrobial agents prescribed were collected. Five-year OS was measured in patients with multiple myeloma (MM), Hodgkin´s lymphoma(HL) and non-Hodgkin´s lymphoma (NHL). Results - The median age was 51 years (18-70) among the 129 patients selected (67 male and 62 female). 63 had MM, 25 HL, 24 NHL, 9 germ cell tumors, 7 acute myeloid leukemia and 1 acute lymphoblastic leukemia. The median of number of CD34+ cells reinfused was 6.02 x 106/kg (2.23-15.7) with 79% (62-93%) of viable cells after defrost. Times to neutrophils and platelets count recovery were 12 (9-18) and 13 (10-21) days, respectively. Three patients showed DMSO-induced reactions. Thirty three patients(25.6%) were treated with antifungal in association with extended spectrum antibiotic. Five-year OS were 57.7% (CI 33.8-71.5) for MM patients, 76.8% (CI 52.5-89.7) for HL and 69.2% (CI 46.9-83.6) for NHL. Conclusions - The collected data provided evidence that the ASCT in Vale do Paraiba has favorable OS rates for patients with MM, HL and NHL in comparison to previously reported data from similar treatment in other regions...