We report an increased incidence of high relapse risk features in 157 APL Brazilian patients. Out of 134 patients treated with ATRA and anthracyclines, only 91 (67.9%) achieved remission because 43 (32%) died during induction. The death rate during consolidation was 10.5%. Bleeding complications were the most frequent cause of failure (21.6%).
We report here the first six cases of leprosy associated with HLA-identical allogeneic SCT in different phases and with different findings and outcomes. Skin and peripheral nerves may be sites of leprosy associated with SCT, stressing the importance of differential diagnosis between leprosy and GVHD or drug reactions. Clinical manifestations of leprosy before or after transplantation did not influence the outcome of SCT in our cases.
RESUMO: Nesta revisão, são discutidos os princípios do diagnóstico e tratamento das principais complicações agudas, não infecciosas, do transplante de células progenitoras hematopoéticas: pancitopenia, incompatibilidade no sistema ABO, mucosite, doença veno-oclusiva hepática, cistite hemorrágica, pneumonite intersticial, cardiotoxicidade e doença do enxerto-contra-hospedeiro aguda. Oito casos clínicos, extraídos da casuística da nossa Unidade de TMO, são descritos brevemente para ilustrar aspectos particulares das doenças discutidas no trabalho.
(i) Allo-HSCT is recommended for high-risk AML (IA); (ii) allo-HSCT is recommended for AML of intermediate risk (IA); (iii) allo-HSCT is recommended for AML relapsed/refractory (C4); (iv) auto-HSCT is recommended for AML after 1 consolidation (C4); (v) auto-HSCT is recommended for AML in CR1 (higher than QT in the Brazilian experience) (C4); (vi) auto-HSCT is accepted for AML M3 in second molecular complete remission (2B); (vii) peripheral blood instead of Bone Marrow HSC for advanced disease (2A); (viii) recommended conditioning protocols: Bu-Cy/Bu-Mel, Bu-Flu, TBI-Cy. In umbilical cord HSCT, consider ATG-based protocols (2A); (ix) allogeneic HSCT for the treatment of AML can be used in patients between 60 and 80 yr with good performance status and the absence of significant comorbidities (C4).
Os autores relatam dois casos de linfoma cutâneo de células B, nos quais o correto estadiamento, tratamento e seguimento foram possíveis graças à combinação de exames convencionais e a cintilografia com gálio-67.
Fludarabine in combination with intravenous Busulfan has been used to reduce treatment related mortality (TRM) in allogeneic stem cell transplantation (SCT). Considering that busulfan has erratic bioavailability and unpredictable intestinal absorption, previous investigations have used intravenous busulfan with plasma-targeted levels dosing. In Brazil neither intravenous Busulfan nor routine plasma level measurement of Busulfan are available. In this report we retrospectively analyze 74 patients (median age 32 y.o.) submitted to SCT using a Fludarabine and oral Busulfan based conditioning regimen. Forty three patients had acute myeloid leukaemia (AML, age range 5 to 58) and 31 patients chronic myeloid leukemia (CML, age range 19 to 58). Among the AML patients, 44% were in first remission (CR1), 23% in second remission (CR2) and 33% patients had active disease (AD) at the time of transplant. Among CML patients, 65% were in chronic phase (CML-CP), 29% in accelerated phase (CML-AP) and 6% in blast crisis (CML-BC). Fludarabine 30 mg/m2 and oral Busulfan 4 mg/kg was given for 4 days with Cyclosporine A and Methotrexate GVHD prophylaxis. For patients with unrelated donors, ATG were added. All patients engrafted (median 14 days). At a median follow up time of 180 days non-relapse mortality was 5%. Seventeen patients (23%) died (12 AML and 5 CML patients). Among survivors (57 patients), 56 remain in complete remission. One patient with a refractory AML and a complex karyotype relapsed on day +90. One patient died of severe sinusoidal obstruction syndrome (SOS). Acute GVHD occurred in 14 (19%) patients (10 AML and 4 CML) none of them grade III or IV. Chronic GVHD occurred in 11 patients so far, being the cause of death in 2 patients. Major cause of death was relapse of disease in patients transplanted with active disease. Only three AML patients in CR1 died (chronic GVHD, sepsis and fulminant hepatic failure) in contrast to 60% of patients with active disease (88% relapsed). One patient with CML-CP died with a relapse in CML-BC, the remaining 19 (92%) patients are alive in complete remission. One patient transplanted in CML-AP died (cGVHD and zygomykosis) and all patients transplanted in BC died of their disease. Actuarial 1-year overall survival for CML is 92% and 54% (CP and AP/BC respectively, p=0,04) and for AML 72% and 23% (CR1/CR2 and AD, respectively, p=0,005). These preliminary data show that oral Busulfan and Fludarabine can safely be used without plasma level monitoring. The follow up time is short and the effect on the control of CML cannot be concluded. However AML has been effectively controlled as far as patients were transplanted in remission (AML-CR1 and CR2). For patients in more advanced disease stages this regimen is not optimal. However, this regimen is safe and may improve the results in early stages of AML and CML even in countries with limited resources in health care.
Acute Promyelocytic Leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML) which has a high prevalence in Latinos as well as a different distribution of PML breakpoints with a higher incidence of bcr1 isoform. We describe here the characteristics and outcome of 148 consecutive patients, from 11 centers in Brazil. Induction consisted of ATRA and anthracyclines (ida or daunorubicin). All centers used anthracyclines in consolidation but association with AraC was variable. Maintenance was based on low dose chemotherapy, except in 2 centers, which were excluded from survival analysis. The incidence of APL among AML was 28.2%. According to the risk stratification from PETHEMA/GIMEMA groups, 58 (39.2%) patients were classified as high risk (HR), 63(42.6%) as intermediate (IR) and 27 (18.2%) as low risk (LR), a higher frequency of HR patients than the reported by Sanz et al analyzing 217 APL patients (p=0.003). A relatively high frequency of early complications was observed, with 26 (17.6%) and 68 (45,9%) patients presenting with life threatening hemorrhage and disseminated intravascular coagulation (DIC), respectively. Early mortality (death in the first 14 days of diagnosis) was higher than the described in developed countries - 42 (28.4%) patients; bleeding (37 patients) was the leading cause. Both early mortality and bleeding were more frequent in the HR group (p=0.002 and <0.001 respectively). From 106 patients alive at D+15, 88 patients survived induction and 73 were alive and in remission after consolidation. One patient relapsed before finishing consolidation and six were still in induction. There was no difference among risk groups in mortality after day 14 of induction. Mean overall survival (OS) for the 133 patients available for analysis was 614 days (CI95% 515–712). Excluding early mortality, mean OS was 844 days (CI95% 741–948). Mean OS was different among the risk groups - 928(785–1071), 748(598–898) and 313(187–439) days for LR, IR AND HR, respectively (p<0.001). Our data suggest that risk classification, besides identification of relapse probability, can identify patients with higher incidence of bleeding, laboratorial DIC and also those that are predisposed to death secondary to hemorrhage and this may alert to the necessity of a more intensive supportive care in induction for this group. Despite the fact that ATRA and anthracyclines are available in Brazil hospitals, these results show that Brazilian patients have a worse outcome than the reported by the latest trials. It is possible that late referral partially accounts for an increased number of high-risk APL among these Brazilian patients. Hence, in addition of specific drugs availability, prompt access to care and initiation of specific therapy is necessary to improve outcome. In this regard, the International Consortium in APL (IC APL), created in 2005 by the International Committee of the American Society of Hematology, aims to implement a network to allow the exchange of experiences among hematologists in developing countries and international specialists as well as to offer real time discussion of newly-diagnosed patients with APL and ongoing complications.
Covid-19 pandemic and Bone Marrow Transplantation
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