philadelphia chromosome-positive acute lymphoblastic leukemia

INTRODUCTION: Tyrosine kinase inhibitors (TKIs) have revolutionized survival rates of chronic myeloid leukemia (CML) and Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) and replaced hematopoietic stem cell transplantation (hSCT) as the key treatment option for these patients. More recently, the so-called Philadelphia chromosome-like (Ph-like) ALL has similarly benefitted from TKIs. However, many patients shift from the first generation TKI, imatinib, due to treatment-related toxicities or lack of treatment efficacy...

We report a case of leukemia cutis showing annular erythema during the course of Philadelphia chromosome-positive acute B-lymphoblastic leukemia. The annular appearance may be developed by immunomodulatory effects of blinatumomab.

BACKGROUND: Although the prognosis of Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) has improved with the introduction of tyrosine kinase inhibitors (TKIs) and stem cell transplantation, prevention of relapse after transplantation remains a concern. The aim of this study was to compare the impact of TKI prophylaxis with imatinib and dasatinib on long-term outcomes after transplantation. METHODS: Patients with Ph+ ALL who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at first complete remission (CR1) and received TKI prophylaxis after allo-HSCT were included in this retrospective analysis...

This study aimed to investigate the usefulness of allogeneic stem cell transplantation (allo-SCT) for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) in the first complete remission (CR1) with complete molecular remission (CMR). We compared the outcomes between Ph+ALL patients who did or did not undergo allo-SCT in CR1. We included patients enrolled in the prospective clinical studies in the tyrosine kinase inhibitor era conducted by the Japan Adult Leukemia Study Group, who achieved CMR within 3 months...

UNLABELLED: Although improved survival in children with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-ALL) has been demonstrated in trials, the outcome appears to be inferior in low- and middle-income countries (LMIC). Methods A file review of children aged ≤ 15 years diagnosed with Ph-ALL from 2010 to 2019 was performed. Minimal residual disease (MRD) was assessed by flow-cytometry. Real-time polymerase chain reaction (qRT-PCR) was used to quantify the BCR::ABL1 transcripts during treatment...

An 18-year-old man underwent allogenic bone marrow transplantation (BMT) for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). Ph+ALL relapsed 3 months after the first BMT, and the patient underwent a second BMT. However, Ph+ALL relapsed 4 months after the second BMT, and he received a haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) from his father. Molecular complete remission was confirmed 29 days after haplo-PBSCT. However, the patient needed dialysis for end-stage renal disease due to thrombotic microangiopathy 3 years and 2 months after haplo-PBSCT...

Acquired point mutations in the ABL1 gene are widely recognized as a cause of Philadelphia chromosome-positive B cell precursor acute lymphoblastic leukemia (Ph+ B-ALL) that is resistant to tyrosine kinase inhibitors, whereas there are few reports about other types of the ABL1 mutation. Here, we report 2 cases of Ph+ B-ALL gaining a partial deletion type mutation of the ABL1 gene (Δ184-274 mutation), which resulted in truncation of the ABL1 molecule and loss of kinase activity. In both cases, the disease was refractory to multiple agents in the recurrent phase after allogeneic hematopoietic cell transplantation...

Introduction The overall survival (OS) of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) has improved with the combination of tyrosine kinase inhibitor (TKI) with intensive chemotherapy. In recent years, there has been increased interest in the possibility of long-term survival without allogeneic hematopoietic stem cell transplantation (HSCT) or maintenance therapy. The aim of this study was to determine the effectiveness of treatment and the resultant outcomes in Ph+ALL patients using real-world data...

BACKGROUND: The combination of low-intensity chemotherapy and inotuzumab ozogamicin (INO), with sequential blinatumomab, is highly effective in older adults with newly diagnosed B-cell acute lymphoblastic leukemia (ALL) and in relapsed or refractory B-cell ALL. Earlier, "dose-dense" administration of blinatumomab could lead to earlier and deeper measurable residual disease (MRD) responses and better outcomes. PATIENTS AND METHODS: We performed a retrospective analysis of the safety and efficacy of a dose-dense regimen of mini-hyper-CVD (mini-hyperfractionated cyclophosphamide, vincristine, and dexamethasone alternating with mini-methotrexate and cytarabine), INO, and blinatumomab in patients with B-cell ALL...

The outcome of Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) has improved significantly following the introduction of the BCR::ABL1 tyrosine kinase inhibitors (TKIs). The addition of newer-generation and more potent TKIs resulted in higher rates of molecular responses and better survival. Achieving a complete molecular remission (CMR; disappearance of the BCR::ABL1 transcripts) within the first 3 months of therapy is an important endpoint in newly diagnosed Ph-positive ALL that identifies patients who have an excellent long-term survival and who may not need to receive an allogeneic hematopoietic stem cell transplantation (HSCT) in first complete remission (CR)...

BACKGROUND/AIM: Acute lymphoblastic leukemia (ALL) is a blood malignancy characterized by a rapid proliferation of lymphoid progenitor cells. Extramedullary relapse (EMR) is the recurrence of leukemia that occurs outside the bone marrow. The central nervous system is the most prevalent site of EMR in ALL, whereas other organs, particularly the renal organs, are less commonly involved. CASE REPORT: A 49-year-old man diagnosed with Philadelphia chromosome-negative ALL (Ph-negative ALL) received a second umbilical cord blood transplant (uCBT) and was confirmed to be in his third hematological complete remission...

Dysregulated hematopoietic niches remodeled by leukemia cells lead to imbalances in immunological mediators that support leukemogenesis and drug resistance. Targeting immune niches may ameliorate disease progression and tyrosine kinase inhibitor (TKI) resistance in Philadelphia chromosome-positive B-ALL (Ph+ B-ALL). Here, we show that T helper type 17 (Th17) cells and IL-17A expression are distinctively elevated in Ph+ B-ALL patients. IL-17A promotes the progression of Ph+ B-ALL. Mechanistically, IL-17A activates BCR-ABL, IL6/JAK/STAT3, and NF-kB signalling pathways in Ph+ B-ALL cells, resulting in robust cell proliferation and survival...

The most important prognostic factor for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) is minimal residual disease (MRD). Previous studies have reported copy number variants of genes such as IKZF1 , CDKN2A/2B , and PAX5 . These gene mutations can be analyzed using multiplex ligation-dependent probe amplification (MLPA), which is less costly and easier to perform than large-scale gene mutation analyses. In this study, we performed copy number variant analysis of leukemia cells at the first onset of Ph+ALL in a case series of allogeneic hematopoietic stem cell transplantation (allo-HSCT) using the MLPA method...

Chronic myeloid leukemia (CML) with BCR-ABL1-positive cells is a myeloproliferative neoplasm (MPN) characterized by a chromosomal translocation t(9,22)(q34.1;q11.2), which results in the formation of a Philadelphia (Ph) chromosome containing the BCR-ABL1 fusion gene. Extramedullary blast crisis (EBC) associated with bcr/abl-positive CML is a rare initial presentation. Here, we present and discuss the case of a 51-year-old man who presented with a weight loss history, cervical swelling, and left-sided abdominal pain...

Recent studies have indicated that more than half of adult patients newly diagnosed with Ph+ ALL can now achieve a cure. However, determining the most suitable protocol for less-resourced settings can be challenging. In these situations, we must consider the potential for treatment toxicity and limited access to newer agents and alloSCT facilities. Currently, it is advisable to use less intensive induction regimens for Ph+ ALL. These regimens can achieve high rates of complete remission while causing fewer induction deaths...

In Philadelphia chromosome-positive B-cell (Ph+) acute lymphoblastic leukemia (LLA), growing evidence has accumulated regarding the efficacy of low-intensity and chemo-free regimens. Our objective was to analyze all recent trials evaluating these treatments and to compare them in terms of efficacy. We applied the Shiny method, an artificial intelligence technique, to analyze Kaplan-Meier curves and reconstruct patient-level data. Reconstructed patient data were then evaluated through standard survival statistics and subjected to indirect head-to-head treatment comparisons...

The advancement and practical use of small-molecule tyrosine kinase inhibitors (TKIs) that specifically target the BCR-ABL fusion protein have introduced a revolutionary era of precision medicine for the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). This review offers a comprehensive exploration of the synthesis, mechanisms of action, and clinical implementation of clinically validated TKIs in the context of BCR-ABL, emphasizing the remarkable strides made in achieving therapeutic precision...

RATIONALE: Imatinib is used in the treatment of Philadelphia chromosome positive (Ph+) leukemias and has been reported to have a direct effect on bone physiology. PRESENTATION: To report on a child with Ph+ acute lymphoblastic leukemia who presented with bilateral flank pain and gross hematuria. DIAGNOSIS: She was diagnosed with obstructive kidney stones 101 days after commencing daily oral imatinib. Stone analysis revealed the presence of calcium phosphate...

SSBP2-CSF1R is an important biomarker for clinical diagnosis and prognosis of Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL). This case report presents a pediatric Ph-like ALL patient carrying the SSBP2-CSF1R fusion gene. The patient was resistant to most conventional chemotherapy regimens and to dasatinib, an inhibitor that has been reported to have a therapeutic effect on SSBP2-CSF1R fusion Ph-like ALL, as she remained minimal residual disease (MRD) positive (detection by flow cytometry) and SSBP2-CSF1R fusion gene (detection by RT-PCR) positive after five rounds of such regimens...

Background: The advent of first- and second-generation BCR/ABL1 tyrosine kinase inhibitors (TKIs), such as imatinib and dasatinib, has markedly improved the clinical outcomes of patients with philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ -ALL). However, due to acquired drug resistance, most Ph+ -ALL patients experience relapse. Thus, third-generation BCR/ABL1 TKIs, including ponatinib and olverembatinib, have been developed with the aim of overcoming drug resistance. Case report : A 79-year-old woman presented with intermittent fever and fatigue for 4 days...