International Journal of Hematology-Oncology and Stem Cell Research
Volume:14 Issue: 3, Jul 2020

The attempt to manage patients with acute myeloid leukemia as outpatients has become increasingly common due to high hospitalization costs, low availability for beds and patient preference. Publications on the subject are scarce, especially in low-income regions and the safety in this population remains to be determined. The present study aims to assess the safety of consolidation with high dose cytarabine in the outpatient setting.

We retrospectively analyzed 39 patients who underwent consolidation with high-dose cytarabine, between 2009 and 2018, at Ophir Loyola Hospital, in Belém, Brazil. Patients treated after 2015 were given high-dose cytarabine as outpatients due to the decision of medical staff.

27 patients received 76 cycles of cytarabine as outpatients; males were 48.14% of the total population, with a median age of approximately 45 years. The occurrence of delay between cycles was significantly lower among outpatients (48.14% vs. 83.33%, p = 0.04). There was no difference between relapse rates, transfusion requirements and non-relapse mortality between both groups. Hospitalization was required in 40.74% of patients during outpatient cycles and 18.51% of blood cultures were positive for pathogens. Non-relapse mortality was significantly higher among patients above 50 years old and treated on an outpatient basis (44.4% vs. 5.60%, p = 0.03).

High-dose cytarabine administration on an outpatient basis appears to be safe and effective in a low-income population at the Brazilian Amazon region, but toxicity seems to be increased for patients older than 50 years.

Cholangiocarcinoma (CCA) is the second most common primary hepatobiliary cancer. These patients have meager prognosis and short-term survival. Precise assessment of glomerular filtration rate is a fundamental aspect of clinical care in cancer patients. Cystatin C has been proposed to be superior to creatinine, a well-known marker of renal function. This study aimed to evaluate cystatin C as a marker of GFR calculation in CCA patients.

One hundred thirty serum samples from CCA patients and 32 from controls were included in this study. Serum cystatin C was measured using immunoturbidity assay. Estimated glomerular filtration rate was calculated by three equations established by chronic kidney disease epidemiology collaboration (based on creatinine and/or cystatin C).

Serum cystatin C in CCA patients was higher than that of controls (p=0.0002). Cystatin C was positively correlated with BUN in CCA group (p=0.019). eGFR based on cystatin C and based on both cystatin C and creatinine in CCA was low with significantly different from those of control (p<0.001). Although there was no difference in eGFR using three equations in control, creatinine based eGFR was high with significantly different from eGFR based on cystatin C and on both creatinine and cystatin C in CCA (P=0.000).  Proportion in each eGFR stage by three equations showed a high sensitivity with significantly different in CCA (p<0.05).

There was a high sensitivity of cys C with significant difference between creatinine and/or cystatin C based eGFR in CCA patients. It should take account into consideration of mild changes in eGFR by cystatin C which is important in managing drug dosage for CCA patients.

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease, usually diagnosed with high index of suspicion. The pathophysiology of TTP is due to severe deficiency of von Willebrand factor cleaving protease, known as ADAMTS 13. Early diagnosis is crucial as without treatment TTP is associated with high mortality rate. Plasma exchange is currently the mainstay of treatment. Nonetheless, the classical pentad of microangiopathic hemolytic anemia (MAHA), thrombocytopenia, neurological dysfunction, kidney dysfunction and fever are seen only in 40 percent of the patients. MAHA and thrombocytopenia are the common presenting features. Presentation with thrombotic complication without hematological features (MAHA and thrombocytopenia) is rare and makes the diagnosis difficult. Herein, we report an unusual presentation of a 53-year-old male, who was initially presented in 2014 with classical features of TTP, however had an atypical presentation of TTP in 2016 with only neurological features without hematological features.

Busulfan (BU) in combination with cyclophosphamide (CY) is used as an effective conditioning regimen in hematopoietic SCT. Busulfan, depletes glutathione level in liver and causes elevated levels of CY metabolites. Cyclophosphamide metabolites are highly toxic for sinusoidal endothelial cells and cause VOD/ SOS with high mortality rate.

All adult patients with acute leukemia, who were candidates for myeloablative allogenic SCT admitted in Stem Cell Transplantation center of our center were enrolled in this prospective randomized clinical trial during 2 years. We tested the hypothesis that reverse administration from BU-CY (28 patients) to CY-BU group (27 patients) would reduce liver toxicity.

Liver function tests were significantly higher in BU-CY group between day -1 and +4 (p<0.05), but we do not have VOD/SOS in both groups. The incidence and severity of acute GVHD was higher in BU-CY group, but not statistically significant. Engraftment and mortality rate were not different.

These data support the concept that CY-BU is associated with less liver toxicity, suggesting CY-BU is superior to BU-CY as conditioning.

Hereditary hemolytic anemias present a unique diagnostic challenge due to their wide phenotypic and genotypic spectrum. Accurate diagnosis is essential to ensure appropriate treatment. We report two cases, which presented as hemolytic anemias, but initial workup was inconclusive and they were finally diagnosed with the help of Next Generation Sequencing (Dehydrated Hereditary Stomatocytosis and Kӧln Hemoglobinopathy). The introduction of gene sequencing to aid diagnosis of these disorders is a revolutionary step forward and should be incorporated earlier in the workup of such patients.

Thymidylate synthase is one of the target enzymes of 5-fluorouracil. However, the clinical and prognostic significance of TS expression in gastric cancer has remained controversial. In this study, the expression of thymidylate synthase was evaluated in gastric cancer patients treated with combinational chemotherapy; moreover, the association between TS expression and clinicopathologic characteristics and overall survival of the patients were also assessed.

In this descriptive study, 89 pathological samples were gathered from patients at Kermanshah hospitals during 2008-2017. The survival status of patients was recorded and their overall survival was evaluated individually.

The average survival period for low and high thymidylate synthase groups was 54 and 50 months, respectively, meaning higher survival time in the lower thymidylate group. But this difference was not statistically significant (log Rank=0.88). In addition, sex, stage, recurrence, and survival had no significant difference between the low and high expression of thymidylate synthase groups (p=0.89).

The results clearly indicated that the level of thymidylate synthase is not a significant modulator of 5- fluorouracil in gastric cancer patients. Nevertheless, evaluation of the level of the enzymes and markers, as well as their effects, is highly recommended for accurate selection of chemotherapeutical strategies.

A trigger for initiation the clonal hematopoietic stem cells disorders could be short telomere length, probably due to chromosomal instability. The relationship between relative telomere length (RTL) and the two linked hematological stem cell disorders, myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), is still unclear.

We evaluated the role of RTL in MDS (n=96) and AML (n=130) at the time of diagnosis using a real time quantitative polymerase chain reaction (RT-PCR) technique. The median value of RTL (1) was set as the cutoff for statistical comparison. Overall survival (OS) is defined as the time from diagnosis to death or last follow-up.

RTL was significantly longer in both MDS and AML cases versus control (p<0.0001) and was significantly longer in MDS versus AML cases (p =0.03). RTL correlated negatively with age in MDS (p <0.0001) but not in AML cases. RTL was also significantly shorter in MDS cases with pancytopenia and poor risk cytogenetics (p < 0.0001 for each) and short RTL was significantly associated with inferior survival (p = 0.007), while RTL showed no significant impact on OS in AML cases. Moreover, short RTL retained independent prognostic value in multivariate analysis (HR= 3.42 [95% CI, 8.97-19.35], p = 0.004).

RTL showed an association with both AML and MDS; however, short RTL was an independent poor prognostic factor in MDS patients only.

Chromosomal breakpoints are the most common cause of hereditary diseases and cancers. Today, many standard clinical methods such as cytogenetic and PCR based techniques are used which have limitation regarding detection resolution. Chromosome conformation capture is a method for detecting gene proximity and chromosomal rearrangements.

In this study, SKW3 cell line was used for detecting t(8;14)(q24;q11) using a  3C-based technique. SKW3 cell line was used for 3C library preparation. For Inverse PCR, two regions were selected in upstream and downstream of the viewpoint locus on chromosome 8-MYC gene based on EcoRI restriction sites. The captured sequence with intra-chromosomal interaction between chr8-c-MYC and chr14-TRD was selected for the translocation PCR primer design.

The DNA fragment captured in 3C PCR showed a specific TRD sequence translocated downstream of the MYC gene. Translocation PCR demonstrated the existence of (8; 14) (q24; q11) MYC /TRD in both library and genomic DNA.

This result demonstrated 3C- based method could be used as a useful low-cost easy operating technique in chromosomal rearrangements detection. In this study, the integration of   whole genome library monitoring and PCR method was used as a high- through put method in chromosomal breakpoints detection.