Rafic Farah

The impact of the omission or inadequate dosing of radiotherapy in extranodal natural killer T-cell lymphoma, nasal type, in the United States: Treatment Selection for NK T-Cell Lymphoma

Extranodal natural killer T‐cell lymphoma, nasal‐type (NKTCL), is a rare malignancy in Western populations and is thus challenging for standardization of care and a prospective study. This study was aimed at defining patterns of care for NKTCL in the context of radiotherapy (RT) use and dose selection in the United States.

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

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.

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.

A phase-1 study of dasatinib plus all-trans retinoic acid in acute myeloid leukemia

Abstract Src family kinases (SFKs) are hyperactivated in acute myeloid leukemia (AML). SFKs impede the retinoic acid receptor, and SFK inhibitors enhance all-trans retinoic acid (ATRA)-mediated cellular differentiation in AML cell lines and primary blasts. To translate these findings into the clinic, we undertook a phase-I dose-escalation study of the combination of the SFK inhibitor dasatinib and ATRA in patients with high-risk myeloid neoplasms. Nine subjects were enrolled: six received 70 mg dasatinib plus 45 mg/m2 ATRA daily, and three received 100 mg dasatinib plus 45 mg/m2 ATRA daily for 28 days. Headache and QTc prolongations were the only two grade 3 adverse events observed. No significant clinical responses were observed. We conclude that the combination of 70 mg dasatinib and 45 mg/m2 ATRA daily is safe with acceptable toxicity. Our results provide the safety profile for further investigations into the clinical efficacy of this combination therapy in myeloid malignancies.

Outcomes of patients diagnosed with acute myeloid leukemia after solid organ transplantation

Organ transplant recipients are at an increased risk for subsequent cancer including acute myeloid leukemia (AML). Treatment of AML following solid transplantation represents a clinical challenge as most patients have significant comorbidities at the time of AML diagnosis. In this study, we evaluated the treatment and outcomes of patients who developed AML following solid organ transplantation at our institution and reviewed the literature on outcomes for these patients. The study cohort consisted of 14 patients (median age 66 years, range 52‐77 years) with newly diagnosed AML following solid organ transplantation. The median interval time between solid organ transplantation and AML diagnosis was 72 months (range 15‐368 months). Seven patients received standard induction chemotherapy, four patients received intermediate type therapy, and the remaining three patients were deemed not fit for therapy and received palliative and supportive care. Six of the 11 treated patients (55%) achieved complete remission (CR). The median overall survival (OS) for all patients was 6 months. The median OS for the patients who achieved complete remission after therapy was 17 months and 2 months for the remaining patients. Despite initial CR, relapse rates are still high, suggesting that alternative strategies for post‐remission therapies are warranted.

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.