Background

Central venous catheters, including peripherally inserted central catheters (PICC), are commonly used during the treatment course of patients (pts) with acute leukemia for the administration of vesicant chemotherapy, infusions, transfusions and blood draws. These catheters increase the risk of deep vein thrombosis (DVT) in the upper extremities and of pulmonary embolism (PE). Anticoagulation therapy (AC) in leukemia pts may be used to treat these thrombotic events. However, pts with this approach may incur an increased risk of bleeding, especially in those with thrombocytopenia. Hence, the benefit versus risk of AC therapy of PICC line-related DVT in pts with acute leukemia is controversial, and there are currently no available guidelines. To our knowledge, this is the first study to examine benefits and risks of AC for PICC line-related DVT in leukemia pts.

Methods

Charts of 37 pts with acute leukemia who developed PICC line-associated DVT at the University of Maryland Greenebaum Cancer Center between 2008 and 2012 were reviewed. Of these, 22 received AC prior to discharge (treatment group) and 15 did not (control group). Of the 22, 20 pts received low molecular weight heparin (LMWH) enoxaparin, low-dose (0.5-0.75 mg/Kg/d) in 7 and high-dose (1.5 mg/Kg/d or 1mg/Kg/bid) in 13. Two pts received fondaparinux and were excluded from analysis, leaving 35 pts. Pts with platelet counts less than 50×103/microL received platelet transfusions to decrease bleeding risk associated with AC. DVT improvement was documented by symptom resolution and/or by imaging. Statistical analyses included Fisher's exact tests, Mann-Whitney U-tests, Kaplan-Meier curves and associated log-rank tests, and Cox Regression Models where appropriate.

Results

Pts and disease characteristics are shown in Table 1 by treatment group. Median follow-up duration was 6 months (range, 0-60 months). DVT developed by 18 days after catheter insertion in 50% of the pts. Status of DVT improvement was known in 30 pts, but missing in 5. In the treatment group, 17 out of 19 (90%) had DVT improvement, compared to 5 out of 11 (45%) in the control group (p = 0.03). Bleeding (non-fatal) occurred in 5 out of 20 (25%) pts in the treatment group, compared to 1 out of 15 (7%) in the control group (p = 0.21). Surviving pts at last follow-up were 14 out of 20 (70%) in the treatment groups and 4 out of 15 (27%) in the control group (p = 0.02). Median survival was not reached in the treatment group but was 9 months in the control group. Kaplan-Meier curve (Figure 1) showed a complete and widening separation in favor of treatment, with a log-rank p-value of 0.02. Unadjusted cox regression models showed a hazard ratio (95% CI) of 0.33 (0.12 – 0.91) in favor of treatment. Adjustment for age, gender, leukemia type, or karyotype did not materially change the results.

Table 1
Treatment group (n = 20)Control group (n = 15)P-value
Median age (yrs) 56 51 0.39 
Gender   0.74 
Female 12  
Male  
Leukemia (no)   0.56 
AML 12 12  
APL  
ALL  
Chemotherapy   0.50 
AML induction (ara-C+anth)  
ATRA+anth  
DNMTI  
Others  
Median initial White-cell count - ×103/microL 8.7 7.6 0.89 
Median initial Platelet count - ×103/microL 59 45 0.93 
Karyotype   0.75 
Favorable  
Intermediate  
Poor  
Initial AC   < 0.001 
None 13  
UFH  
LMWH  
Rivaroxaban  
DVT improved   0.03 
Yes 17  
No  
Unknown  
Bleeding   0.21 
Yes  
No 15 14  
Survived at last follow-up   0.02 
Yes 14  
No 11  
Treatment group (n = 20)Control group (n = 15)P-value
Median age (yrs) 56 51 0.39 
Gender   0.74 
Female 12  
Male  
Leukemia (no)   0.56 
AML 12 12  
APL  
ALL  
Chemotherapy   0.50 
AML induction (ara-C+anth)  
ATRA+anth  
DNMTI  
Others  
Median initial White-cell count - ×103/microL 8.7 7.6 0.89 
Median initial Platelet count - ×103/microL 59 45 0.93 
Karyotype   0.75 
Favorable  
Intermediate  
Poor  
Initial AC   < 0.001 
None 13  
UFH  
LMWH  
Rivaroxaban  
DVT improved   0.03 
Yes 17  
No  
Unknown  
Bleeding   0.21 
Yes  
No 15 14  
Survived at last follow-up   0.02 
Yes 14  
No 11  

Abbreviations: anth: anthracycline, DNMTI: DNA methyltransferase inhibitors, UFH: unfractionated heparin

Conclusions

These observations suggest that acute leukemia pts with catheter-related DVTs may benefit from anticoagulation with platelet transfusion support, and from continuation of therapy after hospital discharge. These findings, although novel, are based on a small number of individuals in a retrospective study. A future prospective study with a larger sample size would be beneficial to confirm these findings.

Disclosures:

No relevant conflicts of interest to declare.

Author notes

*

Asterisk with author names denotes non-ASH members.

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