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The purine nucleoside analogues clofarabine and fludarabine are active in acute myeloid leukemia (AML). We conducted a phase I/II randomized study of idarubicin and cytarabine with either clofarabine (CIA) or fludarabine (FIA) for relapsed or refractory AML. Clofarabine 15 mg/m2 was identified as the recommended phase II dose. Eighty-one patients were assigned using adaptive randomization to CIA (n = 48) or FIA (n = 33). The complete response (CR)/CR without platelet recovery rate did not differ between CIA and FIA (38% versus 30%, respectively; p = .50). In both arms, more than half of patients who had received only one prior line of therapy achieved remission. The median event-free survival for CIA and FIA was 2.0 and 1.9 months (p = .48), and the median overall survival was 6.3 and 4.7 months, respectively (p = .28). No significant differences in adverse events or early mortality rates were observed. Overall, CIA and FIA resulted in similar response rates and survival in patients with relapsed/refractory AML.

Tyrosine kinase inhibitors (TKIs) are teratogenic. Chronic myeloid leukemia (CML) is increasingly identified in younger patients who wish to conceive, the management of CML during pregnancy is challenging. We reviewed 51 pregnancies involving 37 patients (30 women, 10 with >1 pregnancy and 7 men) who were either diagnosed with CML during pregnancy or receiving TKI at the time of conception. Ten women were involved in >1 pregnancies. Fifteen women were diagnosed with CML during pregnancy: 10 were treated with hydroxyurea (n = 5), interferon-alfa (n = 3), leukapheresis (n = 1), or nilotinib (n = 1). There were 14 (82%) healthy babies born on term including 2 sets of twins, 2 spontaneous miscarriages (12%), and 1 elective abortion (6%). Within 1 month of delivery or abortion, all women started TKI and achieved MR4.5 (n = 6) and MMR (n = 8) within 3–48 months. One patient, treated with interferon during pregnancy, died of blast phase within 2 months. Four of the 14 remaining women later conceived 5 other pregnancies while on TKI (3 unplanned, 2 planned). Twenty-six patients (7 men; 19 women) conceived while on TKI, with a total of 36 pregnancies. Fifteen women had 20 unplanned pregnancies while receiving TKI and discontinued immediately upon recognition of pregnancy. The median time of TKI exposure was 3 weeks (range, 2–11). Five pregnancies ended in miscarriages and 3 in elective abortion. All 7 men fathered 7 full-term healthy babies. Of 20 babies born to men and women (including one set of twins), 1 had minor abnormality. Seven women lost their responses during pregnancy but at the end of pregnancy all but 2 resumed TKI and regained responses. Seven women involved in 9 planned pregnancies discontinued TKI prior to conception for a median of 4 months (range, 1–20); 3 lost responses during pregnancy. Only 5 patients resumed therapy after delivery. Outcomes were 6 full-term healthy babies, one premature, and two miscarriages. Conception among CML patients while on TKI could be uncomplicated. While patients may lose response following treatment interruption, nearly all regain response upon resuming therapy. Therapy during pregnancy is rarely needed. [ABSTRACT FROM AUTHOR]

The recurring translocation t(1;19) (q23;p13) with TCF3-PBX1 rearrangements are uncommon in adult acute lymphoblastic leukemia (ALL), and their prognostic impact remains to be described in the era of modern chemotherapies. We investigated 427 adult patients with newly diagnosed pre-B ALL, 16 (4%) had t(1;19)(q23;p13) at diagnosis. All 16 patients achieved complete remission after induction with intensive chemotherapy, and with a median of 7-year follow-up, 2 relapsed. The 5-year cumulative incidence of relapse and overall survival rates were 14% and 82%, respectively. Our analysis showed that adult patients with t(1;19)(q23;p13) positive ALL had favorable prognosis with intensive chemotherapy regimens. [ABSTRACT FROM AUTHOR]

CPX-351 is a dual-drug liposomal encapsulation of cytarabine/daunorubicin. In a phase 3 study (ClinicalTrials.gov Identifier: NCT01696084), patients aged 60–75 years with newly diagnosed, high-risk/secondary AML received 1–2 induction cycles with CPX-351 or 7 + 3 chemotherapy; those achieving complete remission (including with incomplete platelet or neutrophil recovery) could receive up to 2 consolidation cycles with CPX-351 or 5 + 2 chemotherapy, respectively. In this exploratory analysis of the subgroup of patients who received consolidation, median overall survival was prolonged among patients receiving CPX-351 induction/consolidation versus 7 + 3/5 + 2 (25.43 vs. 8.53 months; HR = 0.44 [95% CI: 0.25–0.77]). The safety profile of CPX-351 consolidation was consistent with that of the overall study. Outpatient administration of CPX-351 consolidation occurred in 51%–61% of patients and did not diminish overall survival. These findings suggest consolidation with CPX-351 in this patient population contributed to the prolonged overall survival versus 7 + 3/5 + 2, building upon findings from the overall study population, and provide evidence that, with careful monitoring, some patients can successfully receive CPX-351 as outpatients. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented discussing a study of low-dose azacytidine in patients with chronic myeloid leukemia (CML) who were receiving therapy with tyrosine kinase inhibitors.

Myelosuppression in myelodysplastic syndromes (MDS) is associated with the hypomethylating agent decitabine. A retrospective pooled analysis of two decitabine clinical trials in patients with MDS conducted Cox regression analyses of red blood cell or platelet dependence, myelosuppression, dose modification, cycle delay or dose reduction, and survival effects. In 182 patients, baseline platelet dependence was a predictor for dose modification, reduction or delay, and death (modification: p = 0.006, hazard ratio [HR] = 2.04; reduction/delay: p = 0.011, HR = 2.00; death: p = 0.003, HR = 1.94). Patients with dose modifications had significantly higher overall response rates versus those with none (22% vs. 10%; p = 0.015). Patients with no dose modifications had faster progression to acute myeloid leukemia (AML) versus patients with dose modifications ( p = 0.004). Without dose modifications, patients tended to drop out due to disease progression or other reasons. Decitabine dose modifications on treatment may indicate response to treatment. [ABSTRACT FROM AUTHOR]

We assessed CD30 expression in patients with acute lymphoblastic leukemia (ALL) of either T-cell or B-cell lineage to examine the potential benefit of anti-CD30-targeted therapy in this group of patients. Bone marrow specimens of 34 patients with T- and 44 with B-ALL were assessed for CD30 expression by multicolor flow cytometry immunophenotyping analysis. Of these 78 patients, 75 (96%) were adults; and 63 (81%) had refractory/relapsed disease. Using an arbitrary 20% cut-off, 13/34 (38%) cases of T-ALL and 6/44 (13%) cases of B-ALL were considered to express CD30. In five patients with T-ALL with sequential bone marrow tested, increased CD30 expression was observed during the course of high-dose chemotherapy ( p = 0.025). Philadelphia chromosome/ BCR-ABL1 fusion was positive in 14/44 cases of B-ALL and 2/32 cases of T-ALL, which showed no significant correlation with CD30 expression. In summary, we detected CD30 expression in approximately one-third of patients with T-ALL, and less frequently in B-ALL ( p = 0.017). In T-ALL, CD30 expression is up-regulated during high-dose chemotherapy. These data indicate that anti-CD30-targeted therapy may be a potential option for patients with T-ALL with refractory/relapsed disease. [ABSTRACT FROM AUTHOR]

KIT D816V mutation has been observed in more than 90% of patients with systemic mastocytosis (SM). This mutation constitutively activates the mammalian target of rapamycin (mTOR) signaling pathway. We tested the efficacy of everolimus (RAD001), a novel oral mTOR inhibitor, at a dose of 10 mg daily in an open label, non-comparative Phase II trial for patients with SM. Ten patients were enrolled from April 2007 to October 2008. Median age was 55 years, four were males, seven had indolent and three aggressive SM, and six were previously treated with other agents. Median duration of therapy was 4 months (range 0.2–18). No objective responses were noted. Four patients had a short-lasting subjective improvement in symptoms for a median duration of 3 months (range 3–15). Grade 1–3 diarrhea, mucositis, and neutropenia were the most common adverse effects. No Grade 4 toxicity was noted. In conclusion, everolimus does not result in appreciable clinical activity in patients with SM. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the study of relevance of secondary solid tumors and lymphoma on patients with essential thrombocythemia (ET) and polycythemia vera (PV).

Evaluates the efficacy of fludarabine, cytarabine, cyclophosphamide, cisplatin and GM-CSF (FACPGM) in the treatment of patients with Richter's syndrome. Characteristics of Richter' syndrome; Properties of fludarabine and cytarabine; Toxicity of FACPGM treatment.