ICU intervention during induction chemotherapy for adult patients with newly diagnosed acute myeloid leukemia.

We carried out a retrospective study on newly diagnosed AML patients to identify the risk factors associated with intensive care unit (ICU) intervention. One hundred and twenty consecutive AML patients were included. The median cycle of induction therapy (IT) was 2 (range 1-4). Ten patients (8%) needed ICU intervention during IT. The median time from first IT to ICU transfer was 16days (range 2-88days). Three patients required vasopressor/s, three mechanical ventilation, and four both. The cumulative probability for ICU intervention rose progressively with increasing cycles of IT received, from 2.5% during first induction to 27.5% at fourth induction. Age, sex, presentation white cell counts and coagulation profiles, cytogenetics, pre-chemotherapy ventricular ejection fractions, and prior chemoradiation were not risk factors. Univariate analysis identified a history of inflammatory bowel disease (IBD) (p=0.004) (RR=5.7; p=0.03) and positive blood cultures (BC) (p=0.03) (RR=3; p=0.06) as significant risks. Multivariate analysis found a history of IBD as the only significant factor (p=0.03), while positive BC (p=0.1) trending towards significance. AML patients with a history of IBD and positive BC are at increased risks for ICU intervention during IT.

Outcome of acute myeloid leukemia patients with pulmonary nodules of uncertain etiology receiving allogeneic hematopoietic progenitor cell transplant.

Pulmonary nodules (PNs) develop frequently in patients with acute myeloid leukemia (AML). They are of infectious or inflammatory origin. They pose potential challenges to successful hematopoietic progenitor cell (HPC) transplant as they may be niches for infection reactivation or sites susceptible to subsequent infections. We retrospectively analyzed the outcome of 20 AML patients with multiple PNs who underwent allogeneic HPC transplants (12 related, 8 unrelated). There were 13 males and seven females (median age 52 yrs). Nine patients were in CR1, seven in CR2, and four with residual disease. The median times from appearance of PNs and from last positive CT scans to transplant were three and two months, respectively. The median time from pretransplant CT scans to transplant was one month. Multiple PNs were still reported in 5/20 of the pretransplant scans. The PNs in all five patients did not worsen after transplant. Four patients (one with positive pretransplant CT scan) died within the first 100 d after transplant, but none from primary pulmonary pathology. The median survival of this group of patients was 350 d. Our results, therefore, suggest that multiple PNs of uncertain etiology in patients with AML do not impact adversely on the outcome of allogeneic HPC transplant.

Peri-transplant clostridium difficile infections in patients undergoing allogeneic hematopoietic progenitor cell transplant.

Clostridium difficile infections (CDI) remain the leading cause of infectious diarrhea among hospitalized patients in this country. Patients with hematologic malignancies, especially those who undergo hematopoietic progenitor cell transplants are particularly at risk for developing CDI. One hundred and forty seven consecutive allogeneic hematopoietic progenitor cell transplants were analyzed for peri-transplant Clostridium difficile infections (PT-CDI). Sixteen patients (11%) developed PT-CDI (Median time = 7 days after transplant). The probability for developing PT-CDI during the peri-transplant period was 12.3%. History of CDI was strongly associated with the development of PT-CDI (P = 0.008) (OR = 5.48) (P = 0.017). These patients also developed PT-CDI much earlier than in those without a history (median 1 day vs. 8 days, P = 0.03). The probability for developing PT-CDI for those with a history was 39%. There was a trend toward significance (P = 0.065) between matched related donor grafts and the development of PT-CDI (OR = 0.245) (P = 0.08). Age, sex, diagnosis, transplant preparative regimens, Graft-versus-host disease (GVHD) prophylaxis, grade 3/4 acute GVHD, or use of antimicrobials within 8 weeks of transplant were not associated with PT-CDI. Non-CDI-related deaths occurred in one patient in the PT-CDI group and nine in the group without PT-CDI. In the remaining 139 patients, the length of hospital stay for those with PT-CDI was significantly longer than those without (mean 27 days vs. 22 days; P = 0.02).

Inferior outcome after allogeneic transplant in first remission in high-risk AML patients who required more than two cycles of induction therapy.

While some patients with high-risk acute myeloid leukemia (AML) require one or two cycles of induction chemotherapy to achieve a complete remission (CR), others require more than two cycles. We examined the outcomes of patients with high-risk AML who received allogeneic HPC transplant in CR1. Forty five consecutive high-risk AML patients in CR1 were included. All 45 patients had adverse cytogenetics, FLT 3 mutations, or secondary AML. Group A patients (n = 33) received one or two cycles, and Group B (n = 12) three or more cycles of induction chemotherapy. The patients were comparable in age, sex, white cell count at presentation, and time from diagnosis and from last chemotherapy to transplant. The 100-day mortality rate was higher in Group B patients (50% vs. 9%, P = 0.006). They had a higher non-relapse mortality (33% vs. 6%, P = 0.035) and a longer length of hospital stay from the day of stem cell infusion (median 21 vs. 20, P = 0.02; third quartile 22 vs. 28, P = 0.02). There was also a trend toward inferior event-free survival and overall survival. High-risk AML patients undergoing allogeneic transplant in CR1 after three or more cycles of induction chemotherapy have an inferior outcome and higher mortality when compared to those who only needed one or two cycles of induction chemotherapy. Novel strategies are needed to reduce the transplant-related mortality in high-risk AML patients needing more than two cycles of induction chemotherapy prior to allogeneic transplant in CR1.