Jing-Zhou Hou

Leukapheresis in patients newly diagnosed with acute myeloid leukemia

Hyperleukocytosis is present in 5 to 20 percent of patients with newly diagnosed acute myeloid leukemia (AML). The management of hyperleukocytosis, when symptoms of leukostasis occur, includes intensive supportive care and interventions for rapid cytoreduction. Leukapheresis is a rapid and effective means of cytoreduction and has been used in AML patients. In the current study, we evaluated the outcomes of 68 newly diagnosed AML patients that underwent leukapheresis and the effects of leukapheresis on various laboratory parameters. A total of 127 leukapheresis cycles were performed. The median number of leukapheresis cycles was 2 (range, 1-8). The overall survival for all patients was 4.2 months (95% CI 1.2-9.7 months). The median overall survival for patients who achieved complete remission after induction chemotherapy was significantly higher (19.1 months [95% CI 12.1-41.8 months]) than patients that did not achieve complete remission (0.46 months [95% CI 0.33-0.99 months]). Stepwise logistic regression demonstrated that elevated number of peripheral blasts, low platelet count and elevated bilirubin at AML diagnosis were predictive of death within a week. Leukapheresis was effective in reducing the peripheral blood leukocytes and leukemia blasts and was a safe procedure with regard to organ function, coagulation parameters, red blood cells and platelet count. The high initial response rates in newly diagnosed AML patients fit to receive intensive chemotherapy suggest that leukapheresis could be beneficial in reducing the complications associated with hyperleukocytosis until systemic intensive chemotherapy commences.

IV pentamidine for primary PJP prophylaxis in adults undergoing allogeneic hematopoietic progenitor cell transplant.

IV pentamidine for primary PJP prophylaxis in adults undergoing allogeneic hematopoietic progenitor cell transplant

Fludarabine and cytarabine in patients with acute myeloid leukemia refractory to two different courses of front-line chemotherapy

The most effective regimen for acute myeloid leukemia (AML) patients who do not achieve complete remission (CR) after two different courses of front-line chemotherapy has not been established. We therefore evaluated the efficacy, toxicity, and prognostic factors for achieving CR following treatment with fludarabine and cytarabine in 25 newly diagnosed AML patients who did not respond to initial therapy with idarubicin and cytarabine followed by mitoxantrone and etoposide. CR was achieved in 32% of patients; in 55% of patients with intermediate-risk karyotype and in 14% with unfavorable-risk. Eight percent died of infectious complications. Median duration of overall survival was 6.6 months (95% CI 3.4 months to ∞); 3.4 months (95% CI 0.8-8.6 months) for patients with an unfavorable-risk karyotype and 18.1 months (95% CI 5.0 months to ∞) with an intermediate-risk karyotype (p=0.02). Our data suggest that poor-risk karyotype patients are unlikely to benefit from third course treatment with fludarabine-cytarabine, and that this regimen merits further investigation in AML patients with good or intermediate-risk karyotype that have persistent leukemia after two courses of front-line chemotherapy.

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). Am. J. Hematol. 91:291–294, 2016.

Intensive chemotherapy in patients aged 70 years or older newly diagnosed with acute myeloid leukemia.

Acute myeloid leukemia (AML) represents a major therapeutic challenge in the elderly. Because of the high treatment-related mortality and poor overall outcomes of remission induction therapy, many older patients are not considered candidates for intensive chemotherapy. The current study evaluated prognostic factors for achievement of complete remission (CR) in newly diagnosed elderly AML patients who were treated with initial intensive chemotherapy. The study included 62 newly diagnosed AML patients ≥ 70 years who were treated with intensive chemotherapy. The overall response rate (CR and CRp) was 56%. Patients with favorable or intermediate cytogenetics (p=0.0036) as well as those with primary AML (p=0.0212) had a higher response rate. The median overall survival for all patients was 6.85 months (95% CI 3.7-13.5 months). The median overall survival for patients achieving remission after intensive induction chemotherapy was significantly higher than those who did not respond to therapy (20.4 months vs. 3.5 months, p<0.001). The all-cause 4-week mortality rate was 11%, and the all-cause 8-week mortality rate was 17.7%. A subgroup of elderly patients may benefit more from initial intensive induction chemotherapy, specifically those patients with performance status able to tolerate induction chemotherapy and favorable cytogenetic status. However, despite high rates of initial CR, relapse rates are still high, suggesting that alternative strategies of postremission therapy are warranted.

Patient and family caregiver dyadic adherence to the allogeneic hematopoietic cell transplantation medical regimen

Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative therapy for hematologic disease. To minimize infection risk and poor outcomes post hospital discharge, patients are required to identify a family caregiver to work with them to adhere to the multicomponent post‐HCT medical regimen. In addition to medical surveillance and taking medication as prescribed, the National Marrow Donor Programs recommendations for the first 100 days after HCT include proper catheter care; avoidance of crowds; and reliance on a caregiver for transportation, shopping, and cooking. Frequent, thorough hand washing is also strongly recommended to reduce the risk of bacterial, viral, and fungal infections, and patients typically must monitor their temperature daily to quickly recognize signs of infection. Further, patients who are neutropenic must generally follow a diet that avoids bacteria found in foods, such as fresh fruits and vegetables, salad bars, and fresh deli meats. Despite the importance of adherence, little research has examined levels of adherence or how patients and caregivers manage task requirements. Adherence is particularly critical over the initial period post hospital discharge, when patients are at highest risk for complications and mortality. Studies of adherence to medical regimens in other clinical contexts have focused primarily on the patients role, although family caregivers are often involved. The present study is among the first to describe adherence levels across post‐HCT medical regimen tasks and explore the contribution of dyadic factors to successful adherence in HCT. An additional goal was to describe how post‐HCT

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. Am. J. Hematol. 90:715–718, 2015.

Mitoxantrone and Etoposide for the Treatment of Acute Myeloid Leukemia Patients in First Relapse.

Relapsed acute myeloid leukemia (AML) represents a major therapeutic challenge. Achieving complete remission (CR) with salvage chemotherapy is the first goal of therapy for relapsed AML. However, there is no standard salvage chemotherapy. The current study evaluated outcomes and prognostic factors for achievement of CR in 91 AML patients in first relapse who were treated with the mitoxantrone-etoposide combination regimen. The overall response rate (CR and CRi) was 25%. Factors that were associated with a lower rate of CR included older age, shorter duration of first CR, low hemoglobin, and low platelet count. The median overall survival for all patients was 7.4 months. The survival of patients who achieved CR and underwent allogeneic hematopoietic cell transplantation (allo-HCT) was higher than those who achieved CR and did not undergo allo-HCT (35.3 months vs. 16.8 months, p = 0.057). The median duration of relapse-free survival was 12.7 months in the patients achieving CR. Older age at the time of AML relapse was associated with worse overall survival. The all-cause 4-week mortality rate was 4%, and the all-cause 8-week mortality rate was 13%. The findings of this study underscore the need for newer therapies, especially those that will improve the ability for patients with relapsed AML to achieve CR and to allow them to receive additional therapies.

Location matters in early stage nodal diffuse large B-cell lymphoma

Konstantinos Lontos , Anastasia Tsagianni, Jian-Min Yuan, Daniel P. Normolle, Michael Boyiadzis, Jing-Zhou Hou, Steven H. Swerdlow and Kathleen A. Dorritie Division of Hematology/Oncology, UPMC, Pittsburgh, PA, USA; Division of Internal Medicine, UPMC, Pittsburgh, PA, USA; Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA; UPMC Hillman Cancer Center, Biostatistics Facility, Pittsburgh, PA, USA; UPMC Hillman Cancer Center, Pittsburgh, PA, USA; Department of Pathology, Division of Hematopathology, UPMC, Pittsburgh, PA, USA

Ibrutinib as Treatment for Patients With Relapsed/Refractory Follicular Lymphoma: Results From the Open-Label, Multicenter, Phase II DAWN Study

Purpose The Brutons tyrosine kinase inhibitor ibrutinib has demonstrated clinical activity in B-cell malignancies. The DAWN study assessed the efficacy and safety of single-agent ibrutinib in chemoimmunotherapy relapsed/refractory follicular lymphoma (FL) patients. Methods DAWN was an open-label, single-arm, phase II study of ibrutinib in patients with FL with two or more prior lines of therapy. Patients received ibrutinib 560 mg daily until progressive disease/unacceptable toxicity. The primary objective was independent review committee-assessed overall response rate (ORR; complete response plus partial response). Exploratory analyses of T-cell subsets in peripheral blood (baseline/cycle 3) and cytokines/chemokines (baseline/cycle 2) were performed for available samples. Results Between March 2013 and May 2016, 110 patients with a median of three prior lines of therapy were enrolled. At median follow-up of 27.7 months, ORR was 20.9% (95% CI, 13.7% to 29.7%, which did not meet the 18% lower-bound threshold for the primary end point). Twelve patients achieved a complete response (11%; 95% CI, 5.8% to 18.3%). Median duration of response was 19.4 months (range, 1 to ≥ 33 months), with a median progression-free survival of 4.6 months and a 30-month overall survival of 61% (95% CI, 0.51% to 0.70%). Lymphoma symptoms resolved in 67%. Seven of 32 patients who experienced initial radiologic progression responded upon continuing therapy (pseudoprogression). The most common adverse events were diarrhea, fatigue, cough, and muscle spasms; 48.2% of patients reported serious adverse events. In patients who experienced a response, regulatory T cells were downregulated at C3D1 ( P = .02), and Th1-promoting (antitumor) cytokines interferon-γ and interleukin-12 increased ( P ≤ .035). Conclusion With an ORR of 20.9%, ibrutinib failed to meet its primary efficacy end point in chemoimmunotherapy in patients with relapsed/refractory FL, although responses were durable and associated with a reduction in regulatory T cells and increases in proinflammatory cytokines.