Tor Gunnar Hugo Onsten

Hematopoietic Stem Cell Transplantation for Patients with Mucopolysaccharidosis II

There is limited information regarding the long-term outcomes of hematopoietic stem cell transplantation (HSCT) for mucopolysaccharidosis II (MPS II). In this study, clinical, biochemical, and radiologic findings were assessed in patients who underwent HSCT and/or enzyme replacement therapy (ERT). Demographic data for 146 HSCT patients were collected from 27 new cases and 119 published cases and were compared with 51 ERT and 15 untreated cases. Glycosaminoglycan (GAG) levels were analyzed by liquid chromatography tandem mass spectrometry in blood samples from HSCT, ERT, and untreated patients as well as age-matched controls. Long-term magnetic resonance imaging (MRI) findings were investigated in 13 treated patients (6 ERT and 7 HSCT). Mean age at HSCT was 5.5 years (range, 2 to 21.4 years) in new patients and 5.5 years (range, 10 months to 19.8 years) in published cases. None of the 27 new patients died as a direct result of the HSCT procedure. Graft-versus-host disease occurred in 8 (9%) out of 85 published cases, and 9 (8%) patients died from transplantation-associated complications. Most HSCT patients showed greater improvement in somatic features, joint movements, and activity of daily living than the ERT patients. GAG levels in blood were significantly reduced by ERT and levels were even lower after HSCT. HSCT patients showed either improvement or no progression of abnormal findings in brain MRI while abnormal findings became more extensive after ERT. HSCT seems to be more effective than ERT for MPS II in a wide range of disease manifestations and could be considered as a treatment option for this condition.

Outcome of Treatment in Adult Acute Lymphoblastic Leukemia in Southern Brazil Using a Modified German Multicenter Acute Lymphoblastic Leukemia Protocol

Reports on treatment outcomes in adults with acute lymphoblastic leukemia (ALL) in Brazil are sparse. To evaluate the outcome of patients with ALL managed by the public healthcare system, we studied 42 adults treated from 1990 to 1997 in the Division of Hematology at Hospital de Clínicas, Porto Alegre, Brazil. Of these patients, 14/42 were females and their median age at diagnosis was 26 (17–64) years. The diagnosis of ALL was based on cytological examination of marrow smears, and immunophenotypic and cytogenetic studies, when available. Fifty percent of the patients expressed CD10, 30% were CD10 negative and CD19 positive and 20% expressed T markers. Philadelphia chromosome was found in 4 (7.14%). The chemotherapy protocol was adapted from the German Multicenter ALL (GMALL) 02-84 protocol. The complete remission rate was 93% and the overall survival at 5 years was 41%. No particular risk factor was identified in our series. These results are comparable to the findings of other international studies.

Conventional and high-dose daunorubicin and idarubicin in acute myeloid leukaemia remission induction treatment: a mixed treatment comparison meta-analysis of 7258 patients†

Previous meta‐analyses suggested that acute myeloid leukaemia induction regimens containing idarubicin (IDA) or high‐dose daunorubicin (HDD) induce higher rates of complete remission (CR) than conventional‐dose daunorubicin (CDD), with a possible benefit in overall survival. However, robust comparisons between these regimens are still lacking. We conducted a mixed treatment comparison meta‐analysis regarding these three regimens. Mixed treatment comparison is a statistical method of data summarization that aggregates data from both direct and indirect effect estimates. Literature search strategy included MEDLINE, EMBASE, Cochrane, Scielo and LILACS, from inception until August 2013 and resulted in the inclusion of 17 trials enrolling 7258 adult patients. HDD [relative risk (RR) 1.13; 95% credible interval (CrI) 1.02–1.26] and IDA (RR 1.13; 95% CrI 1.05–1.23) showed higher CR rates than CDD. IDA also led to lower long‐term overall mortality rates when compared with CDD (RR 0.93, 95% CrI 0.86–0.99), whereas HDD and CDD were no different (RR 0.94, 95% CrI 0.85–1.02). HDD and IDA comparison did not reach statistically significant differences in CR (RR 1.00; 95% CrI 0.89–1.11) and in long‐term mortality (RR 1.01, 95% CrI 0.91–1.11). IDA and HDD are consistently superior to CDD in inducing CR, and IDA was associated with lower long‐term mortality. On the basis of these findings, we recommend incorporation of IDA and HDD instead of the traditional CDD as standard treatments for acute myeloid leukaemia induction. The lack of HDD benefit on mortality, when compared with CDD in this study, should be cautiously addressed, because it may have been susceptible to underestimation because of statistical power limitations. Copyright

Quantification of peripheral blood CD34+ cells prior to stem cell harvesting by leukapheresis: a single center experience

Background Due to laboratory logistic issues, our center has traditionally scheduled peripheral blood stem cell harvests based on timing from the start of mobilization. This has proved to be useful in some cases, but also resulted in many fruitless harvests due to poor mobilization. In order to improve the efficiency of collections and compare the effectiveness of peripheral blood CD34+ cells as a predictor with data from other reports, this study analyzed the implementation of this routine. Methods Peripheral blood and leukapheresis samples were quantified by flow cytometry and the association between these parameters was assessed. Results Sixty-six consecutive leukapheresis samples were collected from 34 patients after the collection of peripheral blood samples for CD34+ quantification. A moderate positive correlation was observed between peripheral blood CD34+ cell count and total CD34+ cell count/kg (r = 0.596; p-value < 0.001). A multivariable regression model also confirmed this association and allowed the estimation that for every increase in five CD34+ cells/μL in the peripheral blood, a mean increase of 0.38 × 106 CD34+ cells/kg could be predicted. Demographic characteristics, baseline comorbidities and mobilization regimen did not influence final CD34+ cell count in this sample. Conclusions As observed in other centers, quantification of peripheral blood CD34+ progenitor cells is a strong predictor of effectiveness to guide stem cell harvesting. Due to the results of this study, a modification in the peripheral blood stem cell harvesting logistics was implemented at our center in order to incorporate this routine.

Blood transfusion-related immunomodulation

The phenomenon of transfusion-related immunomodulation (TRIM) has been studied since the observation of a higher kidney allograft survival in patients who had received a higher number of transfusions. Conversely, it has been suggested as one of the possible causes related to the development of infections in patients with multiple blood transfusions and/or after a major surgery, and has been also associated with a decreased function of natural killer cells (NK) and antigen-presenting cells (APCs), reduced cell-mediated immunity, and increased regulatory T cells (Tregs). This review aimed to conceptualize TRIM and discuss some aspects related to its mechanisms and the prevention of immunomodulatory events.

Analysis of the anti-A and anti-B hemagglutinin titers in blood donors from the Hospital de Clínicas de Porto Alegre.

The Editor, The lack of agreement of a predictive critical titer obliges transfusion services to establish local ‘‘cutoffs’’. Quillen et al. propose a strategy to reduce the risk of passive hemolysis by screening plateletpheresis donors for high-titers antibodies [1]. The limited supply of ABO-identical apheresis platelets (APLTS) frequently requires transfusion of non identical APLTS especially of group O donors [2]. Due to differences in anti-A and anti-B titers among ethnic groups [3], we decided to analyze anti-A and antiB (IgG and IgM) of blood donors of groups A, B and O attended at the Hospital de Clínicas de Porto Alegre. IgM antibodies were tittered directly with saline solution in tube and IgG antibodies after pre-treatment with 0.01 DTT for 30–60 min [4] in samples of 437 blood donors. Significant differences in titers were only observed between groups O and B. One thousand five hundred APLTS transfusions are carried out annually. Despite the great number of donors with titers P 1/128 no serious hemolytic reaction has been notified, probably because we routinely titer all group O apheresis donors and use only APLTS with titers < 1/100 in non ABO identical transfusions.

Talidomida e mieloma múltiplo: verificação dos efeitos terapêuticos através de parâmetros clínico e laboratoriais

Over the last two decades, we have seen a radical change in therapy and progression of multiple myeloma, a malignant hematologic disease that is still considered fatal. Recent investment and research on mechanisms that interfere in the physiopathogenesis and bone marrow microenvironment are turning control and regression of the malignant plasma cell clone into something achievable, which may change expectations related to this disease. The new idea of using an old drug, thalidomide, has shown to be effective in multiple myeloma. In 1997, using the known effects of immunomodulation and antiangiogenesis of this drug, clinical trials were started in patients with unresponsive disease. Other therapeutic interventions in the bone marrow microenvironment and plasma cells have been added and proved to be efficacious, not only as a therapy for refractory patients, but also for induction and/or remission maintenance therapy. Thirty-five patients with multiple myeloma were treated with low-dose thalidomide (100 mg) and followed up. Thirteen were on maintenance therapy after bone marrow transplantation, eleven started thalidomide after induction therapy, five after relapse, four were refractory to usual therapies and two had induction therapy with thalidomide. The study took place in the Hematology and Bone Marrow Transplantation service of the Hospital de Clínicas de Porto Alegre, from March 2001 to December 2003. Hemoglobin levels, serum or urine immunoglobulin peaks and bone marrow plasma cell counts were evaluated. These parameters were assessed before starting with the drug and after 3.6 and 12 months of usage. The immunoglobulin level was considered the gold standard to evaluate the response. The results showed that 100 mg was the tolerable dose for 51% of the patients. Sixty-five percent of those who used thalidomide for induction therapy showed a 25 to 50% improvement in immunoglobulin serum levels and 90% of the patients on maintenance therapy (13 after bone marrow transplantation, 11 after induction), sustained the same immunoglobulin levels of the initial plateau. Rev. bras. hematol. hemoter. 2004;26(4):245-255.