Managing chronic myeloid leukemia for treatment-free remission: a proposal from the GIMEMA CML WP

Several papers authored by international experts have proposed recommendations on the management of BCR-ABL1+ chronic myeloid leukemia (CML). Following these recommendations, survival of CML patients has become very close to normal. The next, ambitious, step is to bring as many patients as possible into a condition of treatment-free remission (TFR). The Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA; Italian Group for Hematologic Diseases of the Adult) CML Working Party (WP) has developed a project aimed at selecting the treatment policies that may increase the probability of TFR, taking into account 4 variables: the need for TFR, the tyrosine kinase inhibitors (TKIs), the characteristics of leukemia, and the patient. A Delphi-like method was used to reach a consensus among the representatives of 50 centers of the CML WP. A consensus was reached on the assessment of disease risk (EUTOS Long Term Survival [ELTS] score), on the definition of the most appropriate age boundaries for the choice of first-line treatment, on the choice of the TKI for first-line treatment, and on the definition of the responses that do not require a change of the TKI (BCR-ABL1 6410% at 3 months, 641% at 6 months, 640.1% at 12 months, 640.01% at 24 months), and of the responses that require a change of the TKI, when the goal is TFR (BCR-ABL1 >10% at 3 and 6 months, >1% at 12 months, and >0.1% at 24 months). These suggestions may help optimize the treatment strategy for TFR

Third party cord blood transplant boosts autologous hematopoiesis in a case of persistent bone marrow aplasia after double transplant failure for β-thalassemia major

A 9-year-old female received a double allogeneic stem cell transplant (SCT) from an ABO-incompatible HLA-matched sibling for β-thalassemia major, without achieving a complete donor chimerism. Subsequently, the patient received autologous SCT and five donor lymphocyte infusion, without increasing donor chimerism. After the double transplant failure, we performed an unrelated transplant from a full-matched umbilical cord blood (UCBT). Due to the severe immunosuppression of the patient, we did not administer any conditioning regimen nor GVHD prophylaxis. On day +40 after UCBT, trilinear engraftment was documented. Surprisingly, the hematopoietic reconstitution was related to the re-expansion of the autologous (β-thalassemic) hematopoietic stem cell, as documented by chimerism studies on both peripheral blood and bone marrow. At present, 30 months after UCBT, there is stable hematopoietic autologous reconstitution. This is the first description of the restoration of autologous hematopoiesis obtained with cord blood infusion in a thalassemia-major patient after a double transplant failure

Peg Interferon alpha-2b (Peg Intron) in Essential Thrombocythemia

In Essential Thrombocythemia (ET) patients the optimised pharmacokinetics of the weekly administered pegilated Interferons a (IFN) may increase the compliance to a long-lasting IFN treatment. This phase II study has been designed to evaluate in ET patients efficacy, safety and tolerability of a treatment with Peg Interferon a- 2b (Peg Intron, Schering-Plough). The major objective was to measure the Hematological Response rate (HR = PLTs < 500 x 109/L) after one year of treatment with Peg Intron. Since December 2000, in 16 Hematological Institutions of the Gruppo Italiano Malattie Mieloproliferative Croniche (GIMMC) the Peg Intron treatment has been started in 90 ET patients, 30 Males and 60 Females, median age 45 years (18-72), pretreated with alkylating agents (8%), Hydroxyurea (47%), IFN alpha (30%), Anagrelide (7%) and antiaggregating drugs (93%). At baseline the patients showed: age over 60 (17%), previous thrombosis (7%), platelet count > 1000 x 109/L (81%), peripheral granulocyte precursors (9%), splenomegaly (22%), mean platelet count 1112 x 109/L, mean Hb level 13.4 g/dl, mean WBC count 9.2 x109/L. The median treatment duration was 45 weeks. The initial very low dose of 25 mg/week was scheduled to be increased to 50, 75 and 100 mg/week if the HR was not reached at weeks 13, 26 and 39 respectively . At weeks 13, 26, 39 and 52 the mean platelet count was decreased to 59%, 48%, 44% and 43% of the baseline respectively, the Hematological Response was obtained in 17%, 50%, 72% and 67% of cases as Intention to treat (ITT), while in the patients really receiving Peg Intron the response was reached in 15/88 pts (17%), 45/84 pts (54%), 57/72 pts (79%) and 43/56 pts (77%) respectively. The increase of Peg Intron dose has been performed at weeks 13, 26 and 39 in 83%, 46% and 29% of patients respectively. Dose reduction and transitory interruption of Peg Intron was registered in 7 (8%) and 10 (11%) pts respectively. A drug withdrawal occurred in 8 patients (1 blastic transformation, 2 patient refusal, 2 neurotoxicity, 1 protocol violation, 1 hypertransaminasemia, 1 thyroid cancer ). The toxicity of Peg Intron was WHO grade III (1 case of leukopenia and 1 case of hypertransaminasemia), WHO grade II (mainly represented by leukopenia (9%) and flu-like syndrome (5%)), WHO grade I (mainly as injection syte inflammmation (44%), flu-like syndrome (31%), leukopenia (28%), hypertransaminasemia (14%) and anemia (9%)). Eight patients showed significant alteration of the laboratory thyroid parameters, in 3 cases requiring Peg Intron dose reduction. These preliminary data show that Peg Intron at low dose (median 50 mg/week) is able to induce the Hematological Response in the majority of ET patients, with acceptable safety and toxicity

Oculomotor, Vestibular, and Reaction Time Tests in Mild Traumatic Brain Injury

OBJECTIVE:Mild traumatic brain injury is a major public health issue and is a particular concern in sports. One of the most difficult issues with respect to mild traumatic brain injury involves the diagnosis of the disorder. Typically, diagnosis is made by a constellation of physical exam findings. However, in order to best manage mild traumatic brain injury, it is critically important to develop objective tests that substantiate the diagnosis. With objective tests the disorder can be better characterized, more accurately diagnosed, and studied more effectively. In addition, prevention and treatments can be applied where necessary. METHODS:Two cohorts each of fifty subjects with mild traumatic brain injury and one hundred controls were evaluated with a battery of oculomotor, vestibular and reaction time related tests applied to a population of individuals with mild traumatic brain injury as compared to controls. RESULTS:We demonstrated pattern differences between the two groups and showed how three of these tests yield an 89% sensitivity and 95% specificity for confirming a current diagnosis of mild traumatic brain injury. INTERPRETATION:These results help better characterize the oculomotor, vestibular, and reaction time differences between those the mild traumatic brain injury and non-affected individuals. This characterization will allow for the development of more effective point of care neurologic diagnostic techniques and allow for more targeted treatment which may allow for quicker return to normal activity