Blast Phase Research Articles

Advanced-Stage Chronic Myeloid Leukemia: Options for Difficult Treatment Situations.

A small number of patients with chronic myeloid leukemia (CML) either present with or progress to the accelerated phase (AP) or blast phase (BP). This occurs in approximately 4-7% of patients with CML. Most patients who progress to BP-CML are of myeloid lineage, while approximately 30% are of lymphoid lineage. Due to the rarity of this condition, there are no large or randomized trials that can inform clinical decisions. Most data are from retrospective chart reviews or data from old studies when tyrosine kinase inhibitors (TKIs) were initially approved. In addition, the definition of these categories has been in continuous flux over the last 20 years, making applicability of data even more confusing. In some classifications, the cutoff is 30% blasts for the definition of BP-CML, while in others a cutoff of 20% is used. In addition, more recently the World Health Organization (WHO) classification omitted the accelerated phase and recognized only a two-phase disease, while the International Consensus Classification retained a three-phase definition and retained the accelerated phase. Therapy for patients with AP/BP-CML depends on several factors, including prior therapy, BCR::ABL1 mutation, co-morbidities, cell lineage, and eligibility for allogeneic stem cell transplantation (alloHCT). Patients with AP-CML at presentation have a relatively favorable prognosis and may not need alloHCT if they respond appropriately to therapy. For patients with AP-CML who progressed while on TKI therapy or those with BP-CML, alloHCT is considered the only curative therapy. Our goal is to review the available data on the therapy of patients with AP-CML and BP-CML.

Clinical outcomes in patients in any phase of CML treated with ponatinib in France-Data from the TOPASE observational study.

The TOPASE study was set up to evaluate the outcomes of chronic myeloid leukaemia [CML] patients treated with ponatinib (PON) in a real-world setting in France. One hundred and twenty CML patients, 105 in chronic phase (CP), 8 in accelerated phase (AP) and 7 in blastic phase (BP) were included. Fifty-one (49%) of the CP-CML patients were in third line of treatment. The trigger for PON initiation in CP-CML was 'poor response' in 67 patients, 'poor tolerance' in 28 patients and 'response enhancement' in seven patients. The median dose at initiation was 30 mg/day [Q1; Q3 = 15; 30] in CP-CML and 45 mg/day [Q1; Q3 = 30; 45] in AP/BP-CML. Of 98 CP-CML evaluable patients, 72 (73.5%) were considered as responders (MMR) at one time point at least once, especially for those in second line of treatment and/or presenting a T315I mutation. Ninety-six of 120 (80%) patients reported at least one adverse event. An arterial occlusive event (AOE) was reported in 11 patients (9.2%). Thus, these real-life data confirm the potency of ponatinib in resistant or intolerant patients with an acceptable safety profile in non-selected patients. NCT number: NCT04048564.

Management and Outcomes of Patients Diagnosed with Chronic Myeloid Leukemia in Blast Phase: A Multicenter Analysis By the H Jean Khoury Cure CML Consortium

Management and Outcomes of Patients Diagnosed with Chronic Myeloid Leukemia in Blast Phase: A Multicenter Analysis By the H Jean Khoury Cure CML Consortium

Long-Term Outcomes in Blastic Phase Chronic Myeloid Leukemia - One Center Experience

Long-Term Outcomes in Blastic Phase Chronic Myeloid Leukemia - One Center Experience

Effective Cytoreductive Treatment before Allogeneic Hematopoietic Stem Cell Transplantation May Improve the Outcome of Patients with Blast Phase Myelofibrosis

Effective Cytoreductive Treatment before Allogeneic Hematopoietic Stem Cell Transplantation May Improve the Outcome of Patients with Blast Phase Myelofibrosis

Outcome of Induction Chemotherapy in Acute Lymphoblastic Leukemia in a Resource Constrained Setting

Background: Treatment of acute leukemia requires advanced healthcare setup with availability of advanced diagnostic, blood components and chemotherapeutic agents. In resource constrained settings there are suboptimal facilities for treating acute leukemias leading to early death. Pathwel center of hematology and bone marrow transplant (PATHWEL) is a recently established nonprofit facility for diagnosis and management of blood diseases. This center has adopted certain measures like intensive human resource training, optimizing the use of blood components and chemotherapeutic agents to make the treatment sustainable for poor patients in the limited available resources. Objective: To analyze the outcome of induction chemotherapy in patients with acute lymphoblastic leukemia (ALL) in a -resource constrained setting. Methods: Retrospective observational analysis Patients and Methods: All patients diagnosed as ALL and treated at PATHWEL from March 2022 till June 2024 were included. Medical records of all patients were reviewed and data was collected including patient demographics, disease subtype, induction chemotherapy regimen, response to induction chemotherapy and treatment complications. SPSS software version 23 was used for data analysis. Results: A total of 69 patients with ALL were registered at PATHWEL during the study period. Clinical data and treatment response of 49 patients was available and they were included in this analysis. Out of 49 patients, 42 (86%) were male, 7 (14%) female. Median age was 22 years (range 5 to 58). Thirty-seven patients (75.5%) were newly diagnosed, 7 (14.3%) had relapsed disease, 2 (4.1%) had refractory disease and 3 (6.1%) lymphoid blast transformation of chronic myeloid leukemia (CML). Thirty-five (71.4%) had B-ALL, 10 (20.4%) T- ALL, 3 (6.1%) patients were in lymphoid blast phase of CML and 1 (2%) had acute undifferentiated leukemia. Molecular workup was available for 41 (83.6%) patients out of which 6 (12.2%) were BCR-ABL positive including 3 (6.1%) with de novo ALL and 3 (6.1%) in CML blast transformation, 1 (2%) had TEL-AML1 and the rest had negative molecular panel. Cytogenetics reports were available for 36 (73.4%) out of which 31 (63.2%) were normal, 2 (4.1%) had complex karyotype and one each had double Philadelphia chromosome, Trisomy 8 and hyperdiploidy. All patients except 8, received multiagent induction chemotherapy based on UK-ALI-2011 Regimen B induction, 1 (2%) received modified UKALL 2011 Reg B induction, 6 (12.2%) patients received Fludarabine, cytarabine and daunorubicin/ Idarubicin (FLAG Dauno/Ida) and 2 (4.1%) patients received high dose cytarabine, vincristine, daunorubicin and dexamethasone (Hyper CVAD). Additionally, BCR ABLI positive patients received a tyrosine kinase inhibitor (TKI). The complications were mainly infectious. Twenty-one patients (42.8%) had infectious complications during induction therapy including sepsis in 13 patients (26.5%), neutropenic enterocolitis in 2 cases (4%) and one patient each of pneumocystis pneumonia, viral encephalitis, bacterial meningitis, otitis media, and septic arthritis. Other complications included cardiomyopathy in 1 patient, steroid induced hyperglycemia in 3, proximal myopathy in 1, peripheral neuropathy in 1 and hoarseness of voice with vocal cord mass in 1 case. Thirty-six patients (73.4 %) achieved remission after induction, 6 (12.2%) had refractory disease, and 2 (4%) died during induction, 1(2%) had iatrogenic hypoplasia with residual blasts. Remission status could not be assessed in 4 (8.1%) due to loss to follow up. Conclusion: Our data show encouraging early results of induction chemotherapy in ALL in resource constrained setting by optimizing the available healthcare facilities which is significant as this was a diverse patient population including relapsed and refractory patients. Long term follow up and larger studies may help to refine optimal treatment approach for patients in resource constrained settings.

Efficacy of Combination Blinatumomab and Ponatinib in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL) and Chronic Myeloid Leukemia in Lymphoid Blast Phase (CMLBP) in a Real World Setting

Efficacy of Combination Blinatumomab and Ponatinib in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL) and Chronic Myeloid Leukemia in Lymphoid Blast Phase (CMLBP) in a Real World Setting

Prevention and treatment of transformation of myeloproliferative neoplasms to acute myeloid leukemia.

Philadelphia-chromosome negative (Ph-neg) myeloproliferative neoplasms (MPNs) are hematopoietic stem disorders with a risk of progression to the accelerated-phase (AP) or blastphase (BP) that is influenced by clinical, pathologic, cytogenetic, and molecular variables. Overall survival is limited in MPN-AP/BP with current treatment approaches, particularly in those patients that cannot receive an allogeneic hematopoietic stem cell transplant (allo-HCT). In addition, long-term survival with allo-HCT is predominantly seen in chronic-phase MPNs which suggests that the ideal time for intervention may be before MPNs evolve to AP/BP. Over the course of this review we will focus on the risk factors for progression to MPN-AP/BP, identification of high-risk chronic-phase MPNs, potential early-intervention strategies, and considerations around the timing of allo-HCT. We will also summarize current survival outcomes in MPN-AP/BP, discuss the uncertainty around how to best gauge response to therapy, and outline clinical trial considerations for this patient population. Lastly, we will highlight future directions in the management of high-risk MPNs.

Intensification of upfront chemotherapy for patients with myeloid blast phase CML: a single center experience.

Outcomes for patients with myeloid blast phase chronic myeloid leukemia (CML-MBP) are dismal, and no preferred chemotherapy regimen has been identified. Recent studies have suggested a higher response rate with administration of timed-sequenced regimens (TSR) (purine analog, high-dose cytarabine, anthracycline) in high-risk acute myeloid leukemia patients. We retrospectively evaluated outcomes of newly diagnosed CML-MBP patients consecutively treated at our institution with a TSR or standard-dose cytarabine and an anthracycline ("7 + 3") combined with a tyrosine-kinase inhibitor (TKI) between 2011 and 2023. Endpoints of interest included hematologic response, clinically significant cytogenetic response (CSCR) defined as achieving at least a minor cytogenetic response (Ph + metaphases 0%-≤65%) after induction therapy, event-free survival (EFS), and overall survival (OS). A total of 18 patients with CML-MBP were included of whom 9 (50%) received a TSR and 9 (50%) received "7 + 3". Hematologic response (55.6% vs. 55.6%) and CSCR (25% vs. 37.5%) were similar between TSR- and "7 + 3" treated patients. Twelve patients (66.7%) experienced at least one grade ≥ 3 non-hematologic, end-organ toxicity with 33.3% and 11.1% of TSR- and 7 + 3-treated patients, respectively, experiencing at least two. Our data suggests that intensification of upfront chemotherapy does not appear to improve treatment outcomes in CML-MBP patients however, further studies are warranted to confirm these findings involving a larger cohort.

Ischemic stroke as a presenting feature of promyelocytic blast phase in chronic myeloid leukemia - an uncommon presentation: a case report and literature review in the post imatinib era.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm (MPN characterized by reciprocal translocation in the ABL1 and BCR region of chromosomes 9 and 22 respectively. Progression to the blast phase in chronic myeloid leukemia results in a poorer prognosis. It can be of either myeloid, lymphoid or a mixed lineage. Progression to the promyelocytic blast phase is very rare, and there are no evidence-based guidelines for its management. Thrombosis in CML is not well defined. Thrombosis can be seen in patients with acute promyelocytic leukemia (APL) with venous thrombosis (VTE) being more common than arterial thrombosis. Ischemic stroke as the presenting feature of blast phase progression in CML is extremely rare. We report a case of CML who presented to us with acute ischemic stroke and subsequently was diagnosed as CML transformed to the promyelocytic blast phase. She was successfully treated with dasatinib along with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO).

Case Series: Unveiling mass-forming neoplastic extramedullary hematopoiesis in chronic myeloid leukemia

Abstract Introduction/Objective Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by BCR::ABL1 fusion and predominantly granulocytic proliferation. Three main phases of disease have previously been recognized: chronic, accelerated and blast phase, though accelerated phase has become controversial. During the chronic phase, leukemic cells exist predominantly in the peripheral blood and bone marrow; however, during blast phase, blasts can proliferate in the blood, bone marrow, or extramedullary tissues. Methods/Case Report We present two instances of cutaneous extramedullary hematopoiesis associated with CML at our institution. Results (if a Case Study enter NA) Case 1: A 34-year-old man previously diagnosed with CML presented with painful pustules on his right thigh. Biopsy revealed an infiltration of primarily left-shifted granulocytes, along with scattered megakaryocytes, and rare erythroid precursors. Immunohistochemical studies were consistent with maturing extramedullary hematopoiesis, devoid of sheets or clusters of blasts. Peripheral blood analysis revealed marked neutrophilic leukocytosis with basophilia and eosinophilia. Bone marrow examination depicted left-shifted granulocytic hyperplasia, megakaryocytic hyperplasia, and fewer than 5% blasts. Case 2: A 40-year-old man presented with fatigue, night sweats, weight loss, hepatosplenomegaly and palpable nodules on his left arm and thighs. The biopsy of the thigh nodule uncovered leukemic cells at different developmental stages, along with eosinophils, erythroid precursors, and megakaryocytes. Immunohistochemical staining confirmed their presence, with only a few blasts observed. Blood and bone marrow tests showed leukocytosis with blasts less than 5%, indicating CML in the chronic phase. Molecular analysis confirmed BCR-ABL1 fusion. Conclusion Mass-forming neoplastic extramedullary hematopoiesis in the skin during chronic phase of CML is a feature that is not well-documented in the literature. This entity shows immature granulocytic precursors, but does not exhibit an increase in blasts and therefore should not be called leukemia cutis or myeloid sarcoma. It is important to raise awareness of this entity to prevent misinterpretation as myeloid sarcoma and subsequent unnecessarily aggressive therapy.

CAR-T cells for the treatment of pediatric chronic myeloid leukemia in repeatedly relapsed lymphoid blast phase

Chronic myeloid leukemia presenting de novo in the blast phase (CML-BP) is a rare diagnosis among pediatric malignancies. We report on a 16-year-old male who presented with CML-BP lymphoid at diagnosis. He was treated with shortened acute lymphoblastic leukemia induction plus the tyrosine kinase inhibitor (TKI) imatinib followed by dasatinib. After achieving molecular remission (MR), hematopoietic stem cell transplantation (HSCT) was performed early after diagnosis. Despite prophylactic dasatinib, he relapsed 3 months later with the kinase domain mutation T315I. Multiple therapeutic approaches including ponatinib, blinatumomab, a 2nd HSCT from a different donor, donor lymphocyte infusions, and high-dose asciminib all resulted in subsequent relapse. Another molecular response was achieved by combining ponatinib plus asciminib with chemotherapy. In this situation, CD19-directed CAR-T cells (Kymriah®) were administered for compassionate use and tolerated without adverse events. Compared to all prior therapies, CAR T-cells maintained remission. After 12 months of follow-up, complete B-cell aplasia and low numbers of CAR-T cells are detectable in the peripheral blood, potentially mediating long-term disease control.

Decitabine, venetoclax, and ponatinib for advanced phase chronic myeloid leukaemia and Philadelphia chromosome-positive acute myeloid leukaemia: a single-arm, single-centre phase 2 trial

Advanced phase Philadelphia chromosome-positive myeloid disease-consisting of chronic myeloid leukaemia in the myeloid blast phase and in the accelerated phase, and Philadelphia chromosome-positive acute myeloid leukaemia-is associated with poor outcomes. Although previous studies have suggested the benefit of chemotherapy and BCR::ABL1 tyrosine kinase inhibitor combinations, the optimal regimen is uncertain and prospective studies for this rare group of diseases are scant. Preclinical and retrospective clinical data suggest possible synergy between the BCL-2 inhibitor venetoclax and BCR::ABL1 tyrosine kinase inhibitors. We therefore aimed to design a study to evaluate the safety and activity of a novel combination of decitabine, venetoclax, and the third-generation BCR::ABL1 tyrosine kinase inhibitor ponatinib in advanced phase Philadelphia chromosome-positive myeloid diseases. For this phase 2 study, patients aged 18 years or older with previously untreated or relapsed or refractory myeloid chronic myeloid leukaemia-blast phase, chronic myeloid leukaemia-accelerated phase, or advanced phase Philadelphia chromosome-positive acute myeloid leukaemia, and an Eastern Cooperative Oncology Group performance status of 0-3 were eligible. Patients were eligible regardless of the number of previous lines of therapy received or previous receipt of ponatinib. Cycle 1 (induction) consisted of a 7-day lead-in of ponatinib 45 mg orally daily (days 1-7), followed by combination therapy with decitabine 20 mg/m2 intravenously on days 8-12, venetoclax orally daily with ramp-up to a maximum dose of 400 mg on days 8-28, and ponatinib 45 mg orally daily on days 8-28. Cycles 2-24 consisted of decitabine 20 mg/m2 intravenously on days 1-5, venetoclax orally 400 mg on days 1-21, and ponatinib orally daily on days 1-28. Response-based dosing of ponatinib was implemented in consolidation cycles, with reduction to 30 mg daily in patients who reached complete remission or complete remission with an incomplete haematological recovery and a reduction to 15 mg daily in patients with undetectable BCR::ABL1 transcripts. The primary endpoint was the composite rate of complete remission or complete remission with incomplete haematological recovery in the intention-to-treat population. Safety was assessed in the intention-to-treat population. This trial was registered with ClinicalTrials.gov (NCT04188405) and is still ongoing. Between July 12, 2020, and July 8, 2023, 20 patients were treated (14 with chronic myeloid leukaemia-blast phase, four with chronic myeloid leukaemia-accelerated phase, and two with advanced phase Philadelphia chromosome-positive acute myeloid leukaemia). The median age was 43 years (IQR 32-58); 13 (65%) patients were male and seven (35%) were female; and 12 (60%) were White, three (15%) were Hispanic, four (20%) were Black, and one (5%) was Asian. 12 (60%) patients had received 2 or more previous BCR::ABL1 tyrosine kinase inhibitors, and 14 (70%) patients had at least one high-risk additional chromosomal abnormality or complex karyotype. The median duration of follow-up was 21·2 months (IQR 14·1-24·2). The complete remission or complete remission with an incomplete haematological recovery rate was 50% (10 of 20 patients); complete remission in one [5%] patient and complete remission with incomplete haematological recovery in nine [45%]). An additional six (30%) patients had a morphologic leukaemia-free state. The most common grade 3-4 non-haematological adverse events were febrile neutropenia in eight (40%) patients, infection in six (30%), and alanine or aspartate transaminase elevation in five (25%). Eight (40%) patients had at least one cardiovascular event of any grade. There were three on-study deaths, none of which was considered related to the study treatment and all from infections in the setting of refractory leukaemia. The combination of decitabine, venetoclax, and ponatinib is safe and shows promising activity in patients with advanced phase chronic myeloid leukaemia, including those with multiple previous therapies or high-risk disease features. Further studies evaluating chemotherapy and venetoclax-based combination strategies using newer-generation BCR::ABL1 tyrosine kinase inhibitors are warranted. Takeda Oncology, the National Institutes of Health, and the National Cancer Institute Cancer Center.

T315I – a gatekeeper point mutation and its impact on the prognosis of chronic myeloid leukemia

Abstract Objectives BCR-ABL kinase domain mutations are an important cause of resistance to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukaemia (CML) of which T315I is the most treatment-resilient. This study aimed to observe the frequency of T315I and its impact on disease prognosis in terms of progression and survival. Methods Patients with a response which categorized them into warning zone/or who failed to respond to their TKI treatment completely as per the European LeukemiaNet (ELN) were labeled as non-responders. They were assessed for T315I mutation using Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR) and validated via sequencing. Patients were then longitudinally followed for 96 months for the prognostic impact of the mutation. Results Of the 102 non-responders, T315I mutation was detected in 21.6 % of patients with a female preponderance. Almost 59 % of mutation-harbouring patients were labelled as low Sokal risk at baseline. The disease progression into the blastic phase was reported in 58.8 % of mutation-harbouring patients. Overall survival (study period: 96 months) was 81.8 % in patients harbouring T315I mutation. Patients in the blastic phase had significant odds of harbouring T315I mutation. Conclusions Sub-optimal response or failure to TKI treatment indicates the development of resistance due to the presence of T315I mutation or other mutation(s). Early identification will help redirect the patient’s treatment.

A multicenter phase 2 clinical trial of low-dose subcutaneous decitabine in myelofibrosis

AbstractMyelofibrosis (MF) in the chronic phase is a challenging disease to treat, and conventional treatment options are geared toward symptom palliation. In this prospective, multicenter, phase 2 trial, 21 patients with MF (18 chronic phase, 2 accelerated phase, and 1 blast phase) were treated with a 10-day schedule of subcutaneous decitabine at 0.3 mg/kg per day. The overall response rate was 33% (95% confidence interval, 15-57), primarily manifested as an improvement in cytopenias. The median duration of response was 7 months (range, 3-44). A high International Prognostic Scoring System risk score, high baseline fetal hemoglobin level, and sustained decrease in circulating CD34+ cell counts were associated with response to decitabine. All patients experienced at least 1 grade 3/4 cytopenia. Nonhematologic toxicities were less frequent, with fatigue, anorexia, and hypocalcemia being the most common. Given the lack of effective therapies in MF with severe cytopenias, this study supports further investigation into the use of hypomethylating agents as single agents or in combination therapies. This trial was registered at www.ClinicalTrials.gov as #NCT00095784.

Transplant Outcomes in Myelofibrosis: Impact of Donor Type (Cord Blood Grafts Supported by CD34+ selected Cells [Haplo-Cord] Versus Matched Donors)

BackgroundDespite the established potentially curative role of allogeneic hematopoietic cell transplantation (alloHCT) in managing MF, the choice of alternative donors for patients lacking matched donors remains a challenge, and the optimal graft source in this disease entity continues to be an ongoing debate. ObjectivesWe aimed to evaluate the impact of donor type: umbilical cord blood transplant supported CD34+ haploidentical donor (haplo-cord) vs adult matched related donor (MRD) and matched unrelated donor (MUD) in 40 adult patients with primary or secondary MF, including those progressing to accelerated phase (AP) or blast phase (BP), who underwent their first allo-HCT. The primary objective of this study was to analyze the impact of stem cell source on primary endpoints of overall survival (OS), graft versus host disease (GVHD) and non-relapse mortality (NRM). ResultsMedian follow-up for all alive patients was 53 months (range 0.3-63 months). Nine patients (22.5%) underwent an MRD allo-HCT, 15 patients (37.5%) underwent a MUD allo-HCT, and 16 patients (40%) underwent a haplo-cord allo-HCT. Four patients died without neutrophil engraftment: 3 (19%) in haplo-cord group and one (4%) in MRD/MUD group. The cumulative incidence of ANC engraftment by day 60 was 80% (95%CI 45-94) in the haplo-cord group and 92% (95%CI 65-98) in the MRD/MUD group (p=0.09). The cumulative incidence of platelet engraftment by day 60 was 59% (95%CI 27-81) in haplo-cord group and 75% (95%CI 51-88) in MRD/MUD group (p=0.4). OS was 62% at 1 year (95%CI 49-79) and 34% at 3 years (95%CI 21-55). The 3-yr OS was similar between the haplo-cord group and the MRD/MUD (37% vs 32%, p=0.9). The 1-yr OS for accelerated/blast phase AP/BP patients was 50% (95%CI 27-93) in the haplo-cord group, compared to 40% (95%CI 19-86) in the MRD/MUD. The 1-yr OS for chronic phase CP patients was 83% (95%CI 58-100) in the haplo-cord group, compared to 79% (95%CI 60-100) in the MRD/MUD group. The cumulative incidence of relapse at 3 years in the haplo-cord group was 13% (95%CI 1.8-34), and in the MRD/MUD group was 28% (95%CI 10-49) (p=0.36). 1-yr non-relapse mortality (NRM) was 38% (95%CI 15-61) in the haplo-cord group and 33% (95%CI 15-52) in the MRD/MUD group. 3-yr NRM was 48% (95%CI 19-72) in the haplo-cord group and 54% (95%CI 29-73) in MRD/MUD group(p=0.95). ConclusionWe showed no significant difference in OS, relapse, and NRM outcomes after haplo-cord transplant compared to adult matched donors’ grafts (MRD or MUD) in MF patients. However, there were more graft failures in patients transplanted with a haplo-cord transplants and delayed engraftments with inadequate haplo myeloid bridges. Despite the small sample size in our study, considering our findings and the availability of other alternative donors, using haplo-cord platforms may no longer be justified for myelofibrosis unless the UCB engraftment dynamics can be optimized.

Feasibility of a home-based home videogaming intervention with a family-centered approach for children with cerebral palsy: a randomized multiple baseline single-case experimental design

BackgroundWorldwide, children with cerebral palsy (CP) living in underserved communities face barriers to accessing motor therapy services. This study assessed the implementation and effectiveness of an 8-week, upper limb (UL) home-based intervention with a movement-tracking videogame (Bootle Blast) in Costa Rican children with CP.MethodsChildren established a weekly playtime goal and two UL activities of daily living (ADLs) that they would like to improve on. A multiple-baseline, single-case experimental design, was used with the Performance Quality Rating Scale (PQRS) as the repeated measure to track changes in performance of the selected ADLs between the baseline (usual care) and intervention (Bootle Blast) phases. The Canadian Occupational Performance Measure (COPM), the Box and Blocks Test (BBT) and the Children’s Hand-Use Experience Questionnaire (CHEQ) were collected before and after the intervention. Technical barriers were documented during weekly video calls with a monitoring therapist. Treatment effect size, slope changes and percentage of non-overlapping data were identified for the PQRS. Descriptive statistics summarized results for the BBT, CHEQ, videogame logs (e.g., playtime) and technical barriers.ResultsFifteen children participated and 13 completed the intervention. Both participants who dropped out did so after completing baseline assessments, but before experiencing Bootle Blast. Children’s mean active playtime (i.e., mini-games targeting the UL) across the 8-weeks was 377 min, while mean total time spent engaging with Bootle Blast (active + passive play time [e.g., time navigating menus, reviewing rewards]) was 728 min. In total, eight technical issues (from five children) were reported, and all but three were resolved within 48 h. Partial effectiveness was associated with the intervention. Specifically, 85% of participants improved on the PQRS and 69% achieved clinically important improvements ≥ 2 points in performance on the COPM. Children improved by 1.8 blocks on average on the BBT, while on the CHEQ, five children had a clinically important increase of 10% of the total number of UL activities performed with both hands.ConclusionBootle Blast is a feasible and effective option to facilitate access and engage children with cerebral palsy in UL home rehabilitation.Trial registration Trial registration number: NCT05403567.

The treatment and diagnostic plan for chronic myeloid leukemia in Libyan oncology centers

Background: CML is one of the best understood diseases from the aspect of its cytogenetic abnormalities and the molecular mechanisms involved. CML was the first human disease in which a specific abnormality of the karyotype, the Philadelphia (Ph) chromosome, could be linked to a malignant disease. Later on, it was shown that the Ph chromosome results from a reciprocal translocation between the long arms of chromosomes 9 and 22, which produces the BCR-ABL fusion oncogene. Accordingly, in this study; we are going to determine whether the team workers in Libyan oncology centers actually following these steps of guidelines as it has been used internationally or there are some differences and special circumstances prevent them to apply the guidelines. Objectives: The present study aimed to explore the methods and plans used for diagnosis and treatment of CML patients in Libyan oncology centres and to confirm the most effective methods in diagnosis and treatment of CML by using a statistical analysing of some special data related to a well investigated cases by making a comparison between those plans. Methods: 173 and 153 CML patient files who has registered in Sabratha oncology institute and Misurata oncology institute -which are both considered as the main oncology centers in Libya- during the last sixteen years were investigated. Then, ten CML case files have randomly chosen from total CML patient files (51) and (78) cases from both oncology institutes which represents (35% and 45%) of all cases respectively (Male and Female, five from each institute). All results of laboratory investigations (CBC, biochemistry profiles, blood film, bone marrow, cytogenetic and molecular analysis) have been recorded and statistically analyzed to know the hematological, cytogenetic and molecular responses during the treatment period. CML patients chosen were at varying disease stages (chronic, accelerated, and blastic phases). The drugs used for treatment included 500 mg of Hydroxyurea, 400 mg, 600 mg and 800 mg of Glivec, and 600 mg of Tasigna in rare cases. Results and conclusion: The study has indicated the existence of a clear deficiency gap represented in a widespread lack of many capabilities such as the lack of some devices, equipments, operating materials and qualified experts. Moreover, the study has confirmed that the treatment plan has modified depending on the results of the complete blood count (CBC) only during all periods of the treatment without achieving other important investigation used for treatment follow up such as bone marrow aspiration, blood film examination, cytogenetic examination and molecular diagnostic. This study-as the first study dealing with this important topic- clarified many shortcomings of the diagnostic and treatment plan followed in both oncology institutes. As a recommendation, it is necessary to apply all international standard steps of the diagnosis and treatment in particular.

CML-399 CARDINAL: A Phase 1, Multicenter, Open-Label, Dose-Escalation and Dose-Optimization Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of TERN-701 in Chronic Myeloid Leukemia

ObjectiveDespite improvements in outcomes achieved with BCR::ABL1 active-site-targeting tyrosine kinase inhibitors (TKIs) for treatment of chronic-phase (CP) chronic myeloid leukemia (CML), many patients need to switch treatments due to disease progression, intolerance, or resistance. Because active-site TKIs utilize similar mechanisms of action, novel treatment options are needed for patients. TERN-701 is a highly selective, oral, investigational, allosteric BCR::ABL1 inhibitor specifically targeting the ABL myristoyl pocket. Preclinical data suggest that TERN-701 is highly potent against native BCR::ABL1 and most common BCR::ABL1 mutations, including T315I, acquired with use of second-generation active-site TKIs. CARDINAL (NCT06163430) is an open-label, global, 2-part, phase 1 study evaluating the safety, tolerability, pharmacokinetics (PK), and efficacy of TERN-701 in patients with previously treated CP-CML. MethodsEligible patients are ≥18 years old with an Eastern Cooperative Oncology Group performance status of 0–2, a confirmed diagnosis of BCR::ABL1-positive CP-CML, with or without the T315I mutation, and treatment failure/intolerance of ≥1 prior second-generation TKI (dasatinib, nilotinib, or bosutinib). Patients intolerant of asciminib without overt resistance are eligible. Patients with CML in accelerated or blast phase are ineligible. Patients will receive TERN-701 orally once daily in continuous 28-day cycles. Part 1 (dose escalation) has been initiated and will include ≈24–36 patients assigned to sequential dose-escalation cohorts, starting at 160 mg, and optional backfill cohorts; dose escalation will be guided by a Bayesian optimal interval algorithm. Primary endpoints of Part 1 include incidence of dose-limiting toxicities during the first treatment cycle and other measures of safety and tolerability; secondary endpoints include PK and efficacy measures, such as hematologic and molecular responses. Based upon the results of Part 1, ≥2 TERN-701 dose levels will be selected for further evaluation in Part 2. In Part 2 (dose expansion), ≈40 patients will be randomized to one of the selected dose levels. Part 2 primary endpoints will measure efficacy (hematologic response, molecular response, and best categorical shift in BCR::ABL1 transcript levels from baseline); secondary endpoints include safety, tolerability, and PK. The study is being conducted in the US, Europe, Australia, and South Korea.

Ischemic Stroke as a Presenting Feature of Promyelocytic Blast Phase in Chronic Myeloid Leukemia – an Uncommon Presentation of an Exceptionally Rare Blastic Transformation of Myeloproliferative Neoplasm

Ischemic Stroke as a Presenting Feature of Promyelocytic Blast Phase in Chronic Myeloid Leukemia – an Uncommon Presentation of an Exceptionally Rare Blastic Transformation of Myeloproliferative Neoplasm