Combined chronic myeloid leukaemia and chronic lymphocytic leukaemia in five patients, including one with 17p deletion.

We report a series of five Australian cases of chronic lymphocytic leukaemia (CLL) occurring concurrently with chronic myeloid leukaemia (CML). Patient management including therapies and response together with clinical progress was obtained from medical records and laboratory information systems. Prior to CML diagnosis, all five had a preceding diagnosis of CLL. Three had received prior fludarabine. All received tyrosine kinase inhibitors (TKI). None required subsequent therapy for CLL. One patient had 17p deletion CLL and another patient had normal CLL cytogenetics. All currently have satisfactory blood counts with quantitative polymerase chain reaction for CML showing molecular response. All remain alive. Thus, such cases can be successfully managed by treating each haematological disorder in the usual manner. The control achieved in CML with the TKI enables satisfactory marrow function to recover in patients with concomitant CLL. The role for allograft in patients with dual malignancies is uncertain and needs to be individualised depending on control of each malignancy.

Unrelated Donor Transplant Recipients Given Thymoglobuline Have Superior GRFS When Compared to Matched Related Donor Recipients Undergoing Transplantation without ATG.

Recipients of allogeneic hematopoietic stem cell transplantation (HSCT) from unrelated donors (URDs) and mismatched related donors (MMRDs) typically have a higher incidence of acute and chronic graft-versus-host disease (GVHD) compared with matched related donors (MRDs). Anti-T-cell globulins (ATGs) are often used to reduce GVHD in these recipients. We report the outcomes of 211 adult peripheral blood stem cell transplant recipients with myeloid malignancies who received a standardized transplant protocol, in which ATG (Thymoglobuline 4.5 mg/kg) was administered to recipients of URD and MMRD (n = 147) but not MRD (n = 64) transplant. For all patients, incidence of acute GVHD grades 2 to 4 was 21.4%, and chronic GVHD was 35.0%. Two-year overall survival was 63.2% (95% confidence interval, 55.8% to 71.5%), relapse-free survival was 55.3% (47.4% to 64.6%), and GVHD-free, relapse-free survival (GRFS) was 30.7% (23.2% to 40.8%). There were no differences between recipients of MRDs and other donors in relapse, nonrelapse mortality, and overall and relapse-free survival. However, compared with MRD, recipients from URDs and MMRDs had reduced moderate to severe chronic GVHD (10.4% versus 30.1%, P= .002), less chronic GVHD requiring systemic therapy (19.4% versus 38.9%, P = .006), and superior 2-year GRFS (35.5% versus 20.0%, P = .003). In this retrospective review of nonrandomized transplant groups, outcomes of HSCT performed using an URD with ATG during conditioning were superior to transplant from an MRD without ATG. The addition of Thymoglobuline to conditioning in HSCT from MRD should be further examined in prospective trials.

A case-based discussion of clinical problems in the management of patients treated with ruxolitinib for myelofibrosis.

Ruxolitinib is a dual janus kinase 1 (JAK1)/JAK2 inhibitor used to treat splenomegaly and symptoms associated with myelofibrosis (MF). Current therapeutic options for symptomatic MF include supportive care, myelosuppressive therapy (such as hydroxycarbamide) and janus kinase (JAK) inhibitors (in particular ruxolitinib). Allogeneic stem cell transplantation remains the only potentially curative treatment for MF, and younger transplant-eligible patients should still be considered for allogeneic stem cell transplantation; however, this is applicable only to a small proportion of patients. There is now increasing and extensive experience of the efficacy and safety of ruxolitinib in MF, both in clinical trials and in 'real-world' practice. The drug has been shown to be of benefit in intermediate-1 risk patients with symptomatic splenomegaly or other MF-related symptoms, and higher risk disease. Optimal use of the drug is required to maximise clinical benefit, requiring an understanding of the balance between dose-dependent responses and dose-limiting toxicities. There is also increasing experience in the use of ruxolitinib in the pre-transplantation setting. This paper aims to utilise several 'real-life' cases to illustrate several strategies that may help to optimise clinical practice.

Relationship of CD34+ cells infused and red blood cell transfusion requirements after autologous peripheral blood stem cell transplants: a novel method of analysis.

BACKGROUND: CD34+ cells infused predicts myeloid and platelet engraftment at the time of autologous stem cell transplantation. An association between the number of CD34+ cells infused and erythroid engraftment has yet to be established. STUDY DESIGN AND METHODS: Red blood cells transfused after autologous transplantation were compared with the number of CD34+ cells infused. Myeloid engraftment was assessed to confirm that normal engraftment kinetics occurred. RESULTS: Logistic regression established that the logarithm of the number of CD34+ cells infused (p = 0.0498) and admission hemoglobin (Hb; p < 0.001) predicted the need for transfusion. In those patients who required transfusion, standard regression methods were not valid. A novel model demonstrated that the initial Hb (p < 0.001) and diagnosis (p = 0.047) were significant predictors of transfusion requirements in patients needing transfusion. However, the number of CD34+ cells infused did not predict transfusion requirements in this group (p = 0.226). As myeloid engraftment demonstrated kinetics that have been previously described, it can be inferred that erythroid engraftment was not atypical. CONCLUSION: The number of CD34+ cells infused predicted the need for transfusion, although it did not predict the number of RBCs transfused in those patients having transfusion during their admission for autologous stem cell transplant.

A modelling approach for blood units transfused after stem cell transplantation.

Patients undergoing stem cell transplantation may require transfusion of units (bags) of packed red blood cells (PRBCs). Modelling of PRBC usage is important not only for prediction of transfusion requirements in future patients but also for its use as an inverse surrogate for engraftment, that is transplantation success. Inspection of PRBC unit usage reveals a strong preference for even numbers, which is caused by behavioural preference on the part of prescribing physicians. Digit preference is a phenomenon observed more commonly with self-reported data: typically survey respondents round recalled quantities such as the age at which a life event occurred to multiples of 5 or 10. In all cases, we can conceive of a latent variable, which has a smooth distribution, which is transformed via stochastic rules to a discrete variable with probability spikes at preferred digits. We propose a modelling framework based on a latent variable specification and stochastic transformation to the spiked distribution. Loglinear models for the mean of the process are implemented. Specification of the stochastic rules is important to success in accurate modelling of the process.

Pralatrexate in relapsed/refractory T-cell lymphoma: a retrospective multicenter study.

We present a retrospective multicenter study of pralatrexate treatment outcomes in an Australian practice setting for patients with relapsed/refractory T-cell lymphoma who had failed 1+ systemic therapies, treated via a compassionate access program. Endpoints assessed included response rates, toxicities, and subsequent therapies. Progression-free survival (PFS), time to next treatment (TTNT), event-free survival (EFS), overall survival (OS), and time to best response, were assessed by Kaplan-Meier analysis. The study included 31 patients, with median age 69 years. We demonstrated ORR of 35.5% (n = 11), including 4 complete responses (13%) and 7 partial responses (23%). The predicted median OS was 10 months, with EFS of 9 months, and PFS of 9 months. Median TTNT was 8 months. Mucositis was the most commonly observed toxicity. This study - the second largest real-world cohort reported to date - underscores the importance of pralatrexate in relapsed/refractory T-cell lymphoma, as well as its acceptable toxicity profile.

A randomized trial of high-versus conventional-dose cytarabine in consolidation chemotherapy for adult de novo acute myeloid leukemia in first remission after induction therapy containing high-dose cytarabine.

The value of administering sequential courses of chemotherapy containing high-dose cytarabine in both induction and consolidation therapy for acute myeloid leukemia (AML) has not been assessed in a prospective randomized trial. Two hundred ninety-two AML patients aged 15 to 60 years were enrolled in the Australasian Leukaemia and Lymphoma Group (ALLG) AML trial number 7 (M7) protocol to evaluate this question. All received induction therapy with the ICE protocol (idarubicin 9 mg/m2 x 3; cytarabine 3 g/m2 twice a day on days 1, 3, 5, 7; etoposide 75 mg/m2 x 7). Complete remission was achieved in 234 (80%) patients. Two hundred two patients in remission were then randomized to either a further identical cycle of ICE or 2 attenuated courses (cytarabine 100 mg/m2 daily x 5, idarubicin x 2, etoposide x 5 [IcE]). ICE consolidation therapy was more toxic than IcE, however, the treatment-related death rate was not significantly different. There was no difference between the 2 consolidation arms for relapse-free survival at 3 years (49% for ICE vs 46% for IcE; P = .66), survival following randomization (61% vs 62%; P = .91), or the cumulative incidence of relapse (43% vs 51%; P = .31), and there was no difference within cytogenetic risk groups. Intensive induction chemotherapy incorporating high-dose cytarabine results in high complete remission rates, but further intensive consolidation treatment does not appear to confer additional benefit.