Dysbiosis patterns during re-induction/salvage versus induction chemotherapy for acute leukemia

Abstract Early intracranial hemorrhage (EICH), which is defined by noticeable ICH within 10 days of diagnosis, is a life-threatening hemorrhagic complication in patients with acute leukemia. To ascertain risk factors associated with EICH, we retrospectively analyzed 792 newly-diagnosed acute leukemia patients treated between July 1988 and March 2003. Thirty-one patients (3.9 %) had analyzable EICH. Multivariate analysis showed that female gender (OR = 3.064, P < 0.001), acute promyelocytic leukemia (OR = 8.797, P = 0.003), leukocytosis (OR = 6.056, P = 0.004), and prolonged prothrombin time (OR = 10.026, P = 0.016) were factors significantly associated with occurrence of EICH. Risk scores (RS) were calculated by a product of odds ratio and each risk factor (RF) and taking their sum, generating an RS ranging 0 to 27.943. The cutoff of RS 9 was of statistical significance to predict probability of EICH. Receiver-operating characteristics curve shows the sensitivity and 1 - specificity relative to risk score (AUC = 0.917; S.E. = 0.021; 95% CI, 0.876–0.958; Figure 1). In this regards, RF for EICH was classified as major (prolonged prothrombin time) and minor (female gender, acute promyelocytic leukemia, leukocytosis). Risk model demonstrated that EICH was low probable when no major RF and less than two minor RFs were present. Risk model for ICH in acute leukemia classified acute leukemia patients into two risk groups; low probable EICH group (LPG) and probable EICH group (PG). When applied to our patients, PG was positively correlated with more incidence of FICH than LPG (n = 27/173 vs. 4/619, P < 0.001). Induction chemotherapy could be undertook more frequently in LPG than in PG (p = 0.002, Table 1). Kaplan-Meier curves show the probability of EICH-free survival relative to probability of EICH. ICH-free survival was significantly longer in LPG than in PG (p < 0.0001, Figure 2). Our findings suggest that our risk model may predict the occurrence of EICH in patients with acute leukemia. Table 1. The relationship of risk model and frequency of early intracranial hemorrhage (EICH) or performance of induction chemotherapy. Figure Figure Figure Figure Low probable EICH group, n (%) Probable EICH group, n (%) P EICH (−) 615 (77.7 %) 146 (18.4 %) < 0.001 EICH (+) 4 (0.5 %) 27 (3.4 %) Induction chemotherapy (+) 563 (71.1 %) 143 (18.1 %) 0.002 Induction chemotherapy (−) 56 (7.1 %) 30 (3.8 %)

Download Full-text

Acute Leukemia in Patients Sixty Years of Age and Older: A Retrospective Review.

Blood ◽

10.1182/blood.v106.11.4605.4605 ◽

2005 ◽

Vol 106 (11) ◽

pp. 4605-4605

Author(s):

Chantal S. Leger ◽

Ann Lee ◽

Heather A. Leitch ◽

Paul F. Galbraith ◽

Charles H. Li ◽

...

Keyword(s):

Acute Leukemia ◽

Treatment Outcomes ◽

Induction Chemotherapy ◽

De Novo ◽

Disease Free Survival ◽

Retrospective Chart Review ◽

Prolonged Survival ◽

Entire Group ◽

Secondary Leukemia ◽

Significant Difference

Abstract Acute leukemia, especially acute myeloid leukemia (AML), occurs more frequently in the elderly population. Treatment outcomes for this condition have traditionally been poor and very few patients survive for prolonged periods following diagnosis. We performed a retrospective chart review of all patients sixty years of age and older diagnosed with acute leukemia at St. Paul’s hospital, Vancouver, Canada, from June 1984 to July 2004. One hundred and three patients were diagnosed with acute leukemia [AML- 81; ALL- 15; ALN (acute leukemia not otherwise specified)- 7]. The median age was 72 (range 60–88) years. Fifty-seven (55%) and 46 (45%) patients had de novo and secondary leukemia, respectively. Sixteen patients (28%) had an unfavourable karyotype. Fifty-three patients (51%) received induction chemotherapy (treated) and 50 (49%) were provided with supportive care only (untreated). Treated patients were younger [67 years (60–79)] than untreated patients [76 years (61–88)], (p<0.0001), and no patients >/= 80 years were treated (n=17). Of the treated patients, 33 (62%) achieved a complete remission (CR), 10 (19%) had resistant disease and 10 (19%) died from complications related to treatment. The median overall survival for the entire group was 103 (1–1229) days, and for treated versus untreated patients was 216 (1–1213) and 38 (2–1229) days, respectively (p=0.0021). The disease free survival in treated patients achieving a CR (n=33) was 262 days (9–722). Less than 5% of patients were alive at 4 years from diagnosis. Univariate variables predictive of prolonged survival included receiving induction chemotherapy (p=0.0027), de novo as opposed to secondary leukemia (p=0.0420), and younger age, with a relative increase in death in older subgroups (60–69, 70–79, 80+), (p=0.0311). Induction chemotherapy was the only independent predictor of prolonged survival in multivariate analysis (p=0.0027). There was no statistically significant difference in the number of treated patients and treatment outcomes between 1984–1993 and 1994–2004. In conclusion, this single-institution series of 103 patients aged sixty years and older with acute leukemia, shows that the prognosis of this disease in older patients is extremely poor. Even though induction chemotherapy seems to prolong survival in patients who are fit to receive treatment, the prognosis remains grim and most patients ultimately die of leukemia, supporting a role for investigational regimens focusing solely on this age group. It is no longer appropriate to follow regimens that have remained largely unsuccessful and unchanged over 20 years.

Download Full-text

Cytomegalovirus Infection in Patients with Acute Leukemia and MDS.

Blood ◽

10.1182/blood.v114.22.4167.4167 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4167-4167

Author(s):

Hiromi Yuasa ◽

Taiichi Kyo ◽

Noriaki Yoshida ◽

Yuta Katayama ◽

Hideki Asaoku

Keyword(s):

Acute Leukemia ◽

Induction Chemotherapy ◽

Cytomegalovirus Infection ◽

Conflicts Of Interest ◽

High Dose ◽

Consolidation Chemotherapy ◽

Old Patients ◽

Chemotherapy Induction ◽

Cmv Reactivation ◽

Support Treatment

Abstract Abstract 4167 [Background] It is important for the progress of the support treatment for AML. It is possible for more than seventy years old patients to cure AML actively. [Purpose] We examined the CMV reactivation after chemotherapy of AML, MDS, and ALL. [Methods] The study design planned to enroll 195 patients. Diagnoses included AML (121), MDS (56), ALL (18). Patients received induction chemotherapy. Induction regimens consisted of IDA (12 mg/m2 per day, day 1, 3, 5 and 8) and BHAC (350 mg/ m2 per day, day 1-10)(= Ara-C 200 mg/ m2 per day, day 1-10). Patients received consolidation chemotherapy. Consolidation chemotherapy comprised of High-dose Ara-C Therapy-containing regimens. We examined the CMV reactivation when patients have fever but they were recovered from the leukocyte decrease term after chemotherapy. [Results] About 10% of patients experienced CMV reactivation. Thirteen of 121 AML patients experienced CMV reactivation. Three of 56 MDS patients experienced CMV reactivation. Four of 18 ALL patients experienced CMV reactivation. [Conclusion] It is important to be careful for CMV reactivation in patients receiving High-dose Ara-C Therapy. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Vascular Access Devices: A Retrospective Review Amongst Patients Treated at the Ottawa Hospital with Induction Chemotherapy for Acute Leukemia.

Blood ◽

10.1182/blood.v114.22.4521.4521 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4521-4521

Author(s):

Elie R Skaff ◽

Steve Doucette ◽

Sheryl McDiarmid ◽

Mitchell Sabloff

Keyword(s):

Acute Leukemia ◽

Induction Chemotherapy ◽

Vascular Access ◽

Thrombolytic Agent ◽

Exit Site ◽

Central Venous ◽

Antecubital Fossa ◽

Vascular Access Devices ◽

Ottawa Hospital ◽

The Right

Abstract Abstract 4521 Introduction As part of the care of patients with acute leukemia, central vascular access is important in order to safely and reliably deliver chemotherapy, antibiotics, blood products and nutrition as needed. Two examples of these vascular access devices are peripherally inserted central venous catheters (PICC) and Hickman® catheters (Bard Access Systems, Inc., Salt Lake City, Utah). Each has its set of unique benefits and weaknesses. Some are related to the location where they enter the vascular system but others such as risk of infection, device occlusion or incidence of deep vein thrombosis (DVT) are less clear between devices. Methods Patients included in this study had a diagnosis of acute leukemia (lymphoblastic [ALL] or myeloid [AML]) between September 1996 and April 2009, had a central venous access device inserted (PICC or a Hickman®), received induction chemotherapy and survived at least 20 days. In that time period, the method of insertion of both devices has changed since January 1st 2007. Prior to this date, a specially trained nurse using palpation inserted the PICC at the patient's bedside into veins located in the antecubital fossa (PICC-palp). After this date, the same nursing team began inserting PICCs using ultrasound guidance and modified seldinger technique into veins proximal to the antecubital fossa (PICC-U/S). Hickman® catheters, previously inserted in the operating room by a surgeon (H-Surg), since January 1st 2007 have been inserted in the angiographic suite by an interventional radiologist (H-IR). The four groups were analyzed for differences in basic demographics. Comparisons between the four devices included the presence of cellulitis at the catheter exit site and whether or not there was an infection accompanied at the site, confirmed bacteremia, the need to administer a thrombolytic agent to unblock the device, a DVT around the device, and whether or not the line had to be removed. The four groups were compared for differences using the Kruskal-Wallis Test for continuous variables and the chi-square test for categorical variables. Results 147 patients were identified. 55 had a Hickman® catheter (18 H-Surg and 37 H-IR) and 92 had a PICC (69 PICC-palp and 23 PICC-U/S). The median age (range) within the four groups H-Surg, H-IR, PICC-palp, and PICC-U/S were 54 (20-72), 52 (17-69), 51 (18-73), 56 (19-73), respectively. Males made up 49-56% of each group. ALL ranged between 6 and 9% within each group. The only significant difference between the four groups was whether they were inserted from the right or left side with 89-100% of the Hickman® catheters being inserted on the right vs. 59-74% of the PICCs being inserted on the right (p<0.0001). The most significant improvements from H-Surg to H-IR catheters are the reduction in catheter exit site cellulitis accompanied by exit site infections (27.8% to 5.4%, p=0.04) and in bacteremia counts (72.2% to 27.0%, p=0.01). There were no statistically significant findings from PICC-palp to PICC-U/S; however, the most clinically relevant improvements showed decreases in cellulitis and DVT cases from 60.9% to 39.1% (p=0.07) and 24.6% to 8.7% (p=0.07), respectively. H-IR catheters were shown to outperform PICC-U/S in DVT cases (0.0% vs. 8.7%), and the need to administer a thrombolytic agent (8.1% vs. 69.6%, p<0.0001). upon comparing PICCs vs. Hickman® catheters, the number of catheter exit site cellulitis cases were fewer in the PICC catheters (55.4% vs. 76.4%, p=0.01); however, Hickman® catheters prevailed over PICCs when comparing cases of DVT (0.0% vs. 20.7%) and the need to administer a thrombolytic agent (5.5% vs. 59.8%, p<0.0001). The difference in catheter removal across all four groups was similar ranging from 24-33%. Conclusion Despite small sample groups it appears that both vascular access devices have shown improvements from pre to post 2007 insertion methods. Patients treated at the Ottawa Hospital with intensive chemotherapy for acute leukemia currently appear to demonstrate less complications with Hickman® catheters, inserted by interventional radiologists, compared to PICCs, especially in the most clinically relevant spheres (i.e. bacteremia, incidence of DVT and need for thrombolytic agents to unblock the catheter). This suggests that Hickman® catheters provide a more reliable central vascular access in these patients. A larger sample size or a randomized control trial would be needed to confirm these observations. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Retrospective Review of Invasive Fungal Disease in a Cohort of Patients with Acute Leukemia

Blood ◽

10.1182/blood.v118.21.4265.4265 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4265-4265

Author(s):

Melissa Toupin ◽

Jason Tay ◽

Mitchell Sabloff ◽

Michelle Delbaere ◽

Anne McCarthy

Keyword(s):

Risk Factors ◽

Acute Leukemia ◽

Induction Chemotherapy ◽

Antifungal Agents ◽

Statistical Significance ◽

Invasive Fungal Disease ◽

Fungal Disease ◽

High Grade ◽

Blast Phase ◽

Almost All

Abstract Abstract 4265 Background: Invasive fungal disease (IFD) is a significant cause of morbidity and mortality in patients with acute leukemia (AL). Fluconazole has an established role for prophylaxis in the setting of allogeneic hematopoietic stem cell transplant (AHSCT), and possibly in the setting of acute leukemia. More recently, posaconazole has been shown to reduce the incidence of IFD and mortality in AHSCT recipients, and in patients undergoing chemotherapy for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). However, with increasing use of broader-spectrum antifungal agents, there are concerns regarding breakthrough infections with resistant organisms. Objectives: The first goal of this study is to define the epidemiology of IFD in all patients with acute leukemia, treated at one academic center (The Ottawa Hospital). The second goal is to identify risk factors, which could stratify patients into a very high risk category for the development of IFD. We hope to identify a subset of patients who would benefit from prophylaxis with broader-spectrum antifungal agents. Methods: We performed a retrospective study of adult patients with acute leukemia (including AML, acute lymphoblastic leukemia (ALL), high-grade MDS and blast-phase CML) treated at our institution between May 2009 and April 2011. Patients at all stages of treatment were included. All patients treated with antifungal agents were identified through our pharmacy database. Computerized medical records were reviewed for baseline demographics (age, gender, occupation, diagnosis, days of neutropenia and comorbidities), as well as treatment-related variables (chemotherapy regimen, conditioning regimen, date of AHSCT, response to treatment and presence of GVHD). Imaging, microbiology and biopsy results were also collected. Proven and probable IFD were defined as per the 2008 EORTC/MSG revised criteria. Patient characteristics were compared using Fisher’s exact test. Results: We identified 89 inpatient encounters. Primary diagnosis was AML in 58, high-grade MDS in 15, ALL in 12, blast-phase CML in 3 and PCL in 1 patient. 42 patients were undergoing induction chemotherapy and 10 were undergoing consolidation. 30 patients were post-AHSCT. Contrary to prior studies, all patients were on fluconazole prophylaxis. Out of these 89 encounters, 8 patients (9%) were diagnosed with proven or probable IFD, 12 (13%) met criteria for possible IFD, and the rest (69/89 or 78%) did not meet criteria for IFD. There were 5 probable cases of pulmonary aspergillosis, 1 proven case of hepatic aspergillosis, and 2 proven cases of zygomycosis (1 disseminated and 1 CNS). In terms of risk factors, in our initial analysis, median age was higher in patients with IFD than in patients without (62 vs. 57), though this difference did not reach statistical significance (p = 0.46). There was no difference in the development of IFD based on gender, occupation, days of neutropenia or comorbidities. Although this did not reach statistical significance, almost all patients with IFD had an underlying diagnosis of AML (7/8). In addition, no patients were diagnosed with IFD during consolidation therapy. This is consistent with prior studies. We were not able to assess transplant-related variables, given that only one IFD was diagnosed in a post-AHSCT patient. Overall mortality at 30 days post-admission was significantly higher in the IFD group (6/8 vs. 28/81, p = 0.05). However, only 1 death was directly attributable to the IFD. Otherwise, 3/8 patients with IFD died of refractory leukemia (1 post-AHSCT), 1/8 died of leukemia, 1/8 died of multiorgan failure (not clearly related to IFD), 1/8 survived hepatic aspergillosis and 1/8 survived disseminated mucormycosis. Conclusions: Though limited by sample size, our study indicates that older patients, patients with AML, patients undergoing induction chemotherapy and patients with refractory leukemia may be at highest risk for IFD. In addition, in our cohort, almost all patients with IFD died of their underlying leukemia, while being treated for IFD. It is not clear at this time, but suggestive, that the diagnosis of IFD delayed or interfered with the ongoing treatment plan for some of these patients, possibly contributing to their treatment failure. Therefore, the use of novel antifungal agents would be favored in this group to avoid interruption of leukemia treatment. Further study of this group is currently underway. Disclosures: No relevant conflicts of interest to declare.

Download Full-text