Anticoagulation reaped survival benefit in leukemia patients with DVT

NEW ORLEANS – Continued anticoagulation proved surprisingly beneficial in acute leukemia patients with catheter-related deep vein thrombosis, based on a small retrospective study.

Significantly more patients on anticoagulation had DVT improvement than did those without anticoagulation (17/20 vs. 5/15; P = .03), but they also had significantly better survival (4/20 vs. 4/15).

Median survival has not been reached in the anticoagulation group and was 9 months in controls after a median follow-up of 6 months (P = .02), coauthors Dr. Briana Short and Dr. Nora Oliver reported at the annual meeting of the American Society of Hematology.

The study is one of few to tackle the risks and benefits of anticoagulation in leukemia patients who develop catheter-related DVTs.

There are no currently available guidelines, and the issue remains controversial because catheters increase the risk of DVT and pulmonary embolism, but anticoagulation raises the risk of bleeding in leukemia patients, particularly those with thrombocytopenia, the investigators noted. At many hospitals, the catheter is temporarily removed until the DVT resolves, but this can delay treatment and carries added risks with reinsertion of a central venous catheter.

Nonfatal bleeding events were more common with anticoagulation than without it, but the difference did not reach significance (5 patients vs. 1 patient; P = .21), according to Dr. Short and Dr. Oliver, chief residents at the University of Maryland, Baltimore.

The mechanism behind the increased survival is unknown, but it may be that leukemia patients who experience a DVT have microthrombi or inflammation after chemotherapy, said senior author and colleague Dr. Ashkan Emadi, who developed the novel strategy and also is at the university. A more favorable risk profile among anticoagulated patients was also a very real possibility, prompting the researchers to perform a slew of sensitivity analyses.

"We excluded people with APL [acute promyelocytic leukemia], and the data were still the same. We excluded people with bad cytogenetics, and the data still showed an overall survival benefit," he said in an interview. "We did a lot of rigorous, stingy sensitivity analyses, but wherever we looked, the survival advantage was still there."

The study, which attracted a crowd during the poster session, included 37 patients with acute leukemia who developed a DVT associated with a PICC (peripherally inserted central catheter) line. Half of these occurred within 18 days of catheter placement.

During hospitalization, 21 of the 22 patients in the anticoagulation group were started on unfractionated heparin or low-molecular-weight heparin (LMWH), with the remaining patient started on anticoagulation upon discharge. Two patients were anticoagulated with fondaparinux (Arixtra) and excluded from the analysis.

Two of the 15 controls were initially started on anticoagulation, but the therapies were discontinued during their hospital stay.

At discharge, 7 patients received enoxaparin (Lovenox) LMWH 0.5-0.75 mg/kg per day, and 13 received enoxaparin 1.0-1.5 mg/kg per day, both for 3 months. Patients were maintained at a platelet count of 50 x 10³/mcL, and received platelet transfusions to decrease the risk of bleeding, if counts fell below this level. Controls were monitored post discharge by the treating physician without receiving any anticoagulation.

At baseline, the anticoagulated patients and controls were similar with respect to age (median, 56 vs. 51 years); presence of acute myeloid leukemia (12 each), acute promyelocytic leukemia (6 vs. 2 patients), or acute lymphoblastic leukemia (2 vs. 1 patient); poor-risk karyotype (5 vs. 4 patients); initial median white cell count (8.7 x 10³/mcL vs. 7.6 x 10³/mcL); and initial median platelet count (59 x 10³/mcL vs. 45 x 10³/mcL).

Though provocative, the findings need to be replicated in a prospective study, currently under discussion with researchers from Johns Hopkins Hospital, Baltimore, and Massachusetts General Hospital, Boston, Dr. Emadi said.

The authors reported having no financial disclosures.

pwendling@frontlinemedcom.com

NEW ORLEANS – Continued anticoagulation proved surprisingly beneficial in acute leukemia patients with catheter-related deep vein thrombosis, based on a small retrospective study.

Significantly more patients on anticoagulation had DVT improvement than did those without anticoagulation (17/20 vs. 5/15; P = .03), but they also had significantly better survival (4/20 vs. 4/15).

Median survival has not been reached in the anticoagulation group and was 9 months in controls after a median follow-up of 6 months (P = .02), coauthors Dr. Briana Short and Dr. Nora Oliver reported at the annual meeting of the American Society of Hematology.

The study is one of few to tackle the risks and benefits of anticoagulation in leukemia patients who develop catheter-related DVTs.

There are no currently available guidelines, and the issue remains controversial because catheters increase the risk of DVT and pulmonary embolism, but anticoagulation raises the risk of bleeding in leukemia patients, particularly those with thrombocytopenia, the investigators noted. At many hospitals, the catheter is temporarily removed until the DVT resolves, but this can delay treatment and carries added risks with reinsertion of a central venous catheter.

Nonfatal bleeding events were more common with anticoagulation than without it, but the difference did not reach significance (5 patients vs. 1 patient; P = .21), according to Dr. Short and Dr. Oliver, chief residents at the University of Maryland, Baltimore.

The mechanism behind the increased survival is unknown, but it may be that leukemia patients who experience a DVT have microthrombi or inflammation after chemotherapy, said senior author and colleague Dr. Ashkan Emadi, who developed the novel strategy and also is at the university. A more favorable risk profile among anticoagulated patients was also a very real possibility, prompting the researchers to perform a slew of sensitivity analyses.

"We excluded people with APL [acute promyelocytic leukemia], and the data were still the same. We excluded people with bad cytogenetics, and the data still showed an overall survival benefit," he said in an interview. "We did a lot of rigorous, stingy sensitivity analyses, but wherever we looked, the survival advantage was still there."

The study, which attracted a crowd during the poster session, included 37 patients with acute leukemia who developed a DVT associated with a PICC (peripherally inserted central catheter) line. Half of these occurred within 18 days of catheter placement.

During hospitalization, 21 of the 22 patients in the anticoagulation group were started on unfractionated heparin or low-molecular-weight heparin (LMWH), with the remaining patient started on anticoagulation upon discharge. Two patients were anticoagulated with fondaparinux (Arixtra) and excluded from the analysis.

Two of the 15 controls were initially started on anticoagulation, but the therapies were discontinued during their hospital stay.

At discharge, 7 patients received enoxaparin (Lovenox) LMWH 0.5-0.75 mg/kg per day, and 13 received enoxaparin 1.0-1.5 mg/kg per day, both for 3 months. Patients were maintained at a platelet count of 50 x 10³/mcL, and received platelet transfusions to decrease the risk of bleeding, if counts fell below this level. Controls were monitored post discharge by the treating physician without receiving any anticoagulation.

At baseline, the anticoagulated patients and controls were similar with respect to age (median, 56 vs. 51 years); presence of acute myeloid leukemia (12 each), acute promyelocytic leukemia (6 vs. 2 patients), or acute lymphoblastic leukemia (2 vs. 1 patient); poor-risk karyotype (5 vs. 4 patients); initial median white cell count (8.7 x 10³/mcL vs. 7.6 x 10³/mcL); and initial median platelet count (59 x 10³/mcL vs. 45 x 10³/mcL).

Though provocative, the findings need to be replicated in a prospective study, currently under discussion with researchers from Johns Hopkins Hospital, Baltimore, and Massachusetts General Hospital, Boston, Dr. Emadi said.

The authors reported having no financial disclosures.

pwendling@frontlinemedcom.com

NEW ORLEANS – Continued anticoagulation proved surprisingly beneficial in acute leukemia patients with catheter-related deep vein thrombosis, based on a small retrospective study.

Significantly more patients on anticoagulation had DVT improvement than did those without anticoagulation (17/20 vs. 5/15; P = .03), but they also had significantly better survival (4/20 vs. 4/15).

Median survival has not been reached in the anticoagulation group and was 9 months in controls after a median follow-up of 6 months (P = .02), coauthors Dr. Briana Short and Dr. Nora Oliver reported at the annual meeting of the American Society of Hematology.

The study is one of few to tackle the risks and benefits of anticoagulation in leukemia patients who develop catheter-related DVTs.

There are no currently available guidelines, and the issue remains controversial because catheters increase the risk of DVT and pulmonary embolism, but anticoagulation raises the risk of bleeding in leukemia patients, particularly those with thrombocytopenia, the investigators noted. At many hospitals, the catheter is temporarily removed until the DVT resolves, but this can delay treatment and carries added risks with reinsertion of a central venous catheter.

Nonfatal bleeding events were more common with anticoagulation than without it, but the difference did not reach significance (5 patients vs. 1 patient; P = .21), according to Dr. Short and Dr. Oliver, chief residents at the University of Maryland, Baltimore.

The mechanism behind the increased survival is unknown, but it may be that leukemia patients who experience a DVT have microthrombi or inflammation after chemotherapy, said senior author and colleague Dr. Ashkan Emadi, who developed the novel strategy and also is at the university. A more favorable risk profile among anticoagulated patients was also a very real possibility, prompting the researchers to perform a slew of sensitivity analyses.

"We excluded people with APL [acute promyelocytic leukemia], and the data were still the same. We excluded people with bad cytogenetics, and the data still showed an overall survival benefit," he said in an interview. "We did a lot of rigorous, stingy sensitivity analyses, but wherever we looked, the survival advantage was still there."

The study, which attracted a crowd during the poster session, included 37 patients with acute leukemia who developed a DVT associated with a PICC (peripherally inserted central catheter) line. Half of these occurred within 18 days of catheter placement.

During hospitalization, 21 of the 22 patients in the anticoagulation group were started on unfractionated heparin or low-molecular-weight heparin (LMWH), with the remaining patient started on anticoagulation upon discharge. Two patients were anticoagulated with fondaparinux (Arixtra) and excluded from the analysis.

Two of the 15 controls were initially started on anticoagulation, but the therapies were discontinued during their hospital stay.

At discharge, 7 patients received enoxaparin (Lovenox) LMWH 0.5-0.75 mg/kg per day, and 13 received enoxaparin 1.0-1.5 mg/kg per day, both for 3 months. Patients were maintained at a platelet count of 50 x 10³/mcL, and received platelet transfusions to decrease the risk of bleeding, if counts fell below this level. Controls were monitored post discharge by the treating physician without receiving any anticoagulation.

At baseline, the anticoagulated patients and controls were similar with respect to age (median, 56 vs. 51 years); presence of acute myeloid leukemia (12 each), acute promyelocytic leukemia (6 vs. 2 patients), or acute lymphoblastic leukemia (2 vs. 1 patient); poor-risk karyotype (5 vs. 4 patients); initial median white cell count (8.7 x 10³/mcL vs. 7.6 x 10³/mcL); and initial median platelet count (59 x 10³/mcL vs. 45 x 10³/mcL).

Though provocative, the findings need to be replicated in a prospective study, currently under discussion with researchers from Johns Hopkins Hospital, Baltimore, and Massachusetts General Hospital, Boston, Dr. Emadi said.

The authors reported having no financial disclosures.

pwendling@frontlinemedcom.com