Phase Chronic Myeloid Leukemia Research Articles

Health care resource utilization in 3L + patients with chronic phase chronic myeloid leukemia receiving asciminib or bosutinib

ObjectivesTo assess and compare health care resource utilization (HCRU) rates of asciminib and bosutinib at the Week 24, Week 48, and Week 96 cutoffs among 3 L + patients with chronic myeloid leukemia in chronic phase (CML-CP) in the randomized ASCEMBL trial.MethodsPatients in the ASCEMBL trial (Clinicaltrials.gov: NCT03106779) were randomized to receive asciminib 40 mg twice daily (n = 157) or bosutinib 500 mg once daily (n = 76). At each scheduled visit, investigators conducted HCRU assessment on hospitalization, emergency room visit, general practitioner visit, specialist visit and urgent care visit; duration and type of hospitalization for the hospitalized patients; and reasons for HCRU. The number of patients with HCRU, rate of HCRU per patient-year, and length of hospital stay by ward type were compared at Week 24, Week 48, and Week 96 analyses.ResultsLower proportions of patients receiving asciminib versus bosutinib used any resources including hospitalizations, emergency room visits, general practitioner visits, specialist visits, and urgent care visits (23.6% versus 36.8%, 26.1% versus 39.5%, and 28.6% versus 42.6% at Week 24, Week 48, and Week 96 analyses, respectively). After normalizing for treatment exposure, rates of HCRU for any resource per patient-year were significantly lower for asciminib versus bosutinib: 0.25 (95% CI: 0.18–0.34) versus 0.80 (95% CI: 0.55–1.16) at the Week 24 analysis, 0.20 (95% CI: 0.15–0.27) versus 0.47 (95% CI: 0.32–0.66) at the Week 48 analysis, and 0.17 (95% CI: 0.12–0.22) versus 0.40 (95% CI: 0.27–0.55) at the Week 96 analysis. Among the hospitalized patients, mean length of hospital stay was lower for asciminib than bosutinib for most wards at all three timepoints.ConclusionsIn the ASCEMBL trial, asciminib-treated patients with CML-CP in 3 L + maintained lower resource utilization compared to bosutinib over the long-term.

Response-Based Dosing for Ponatinib: Model-Based Analyses of the Dose-Ranging OPTIC Study.

Optimizing Ponatinib Treatment in CP-CML (OPTIC) was a randomized, phase II dose-optimization trial of ponatinib in chronic phase-chronic myeloid leukemia (CP-CML) resistant to ≥ 2 tyrosine kinase inhibitors or with T315I mutation. Patients were randomized to starting doses of 45-, 30-, or 15-mg ponatinib once daily. Patients receiving 45- or 30-mg reduced to 15-mg upon achievement of ≤ 1% BCR::ABL1IS (≥ molecular response with 2-log reduction (MR2)). The exposure-molecular response relationship was described using a four-state, discrete-time Markov model. Time-to-event models were used to characterize the relationship between exposure and arterial occlusive events (AOEs), grade ≥ 3 neutropenia, and thrombocytopenia. Increasing systemic exposures were associated with increasing probability of transitioning from no response to ≥ MR1, and from MR1 to ≥ MR1, with odds ratios of 1.63 (95% confidence interval (CI), 1.06-2.73) and 2.05 (95% CI, 1.53-2.89) for a 15-mg dose increase, respectively. Ponatinib exposure was a significant predictor of AOEs (hazard ratio (HR) 2.05, 95% CI, 1.43-2.93, for a 15-mg dose increase). In the exposure-safety models for neutropenia and thrombocytopenia, exposure was a significant predictor of grade ≥ 3 thrombocytopenia (HR 1.31, 95% CI, 1.05-1.64, for a 15-mg dose increase). Model-based simulations predicted a clinically meaningful higher rate of ≥ MR2 response at 12 months for the 45-mg starting dose (40.4%) vs. 30-mg (34%) and 15-mg (25.2%). The exposure-response analyses supported a ponatinib starting dose of 45 mg with reduction to 15 mg at response for patients with CP-CML.

Treg Cells, FoxP3 and TGF-β Expression and Significance in Chronic Myeloid Leukemia

To investigate the expression and significance of regulatory T cells (Tregs), FoxP3 and transforming growth factor-β (TGF-β) in different phase of chronic myeloid leukemia (CML). Peripheral blood of 73 CML patients in Department of Hematology, Heze Municipal Hospital from March 2018 to March 2021 were collected. According to patient's period in CML, they were divided into ND CML group (newly diagnosed), CP CML group (chronic period), and BP CML group (blast phase). The percentage of Tregs, expression level of FoxP3 mRNA and TGF-β were detected by flow cytometry, RT-qPCR, and ELISA, respecitively. The roles of above indices in clinical pathogenesis of patients with CML were analyzed. The proportion of Treg in the ND CML group was slightly higher than the CP CML group, but the difference was not statistically significant (P =0.695), while the BP CML group was significantly higher than the other two groups (P =0.008, P <0.001). The expression levels of FoxP3 mRNA in ND CML group, CP CML group and BP CML group were 11.61±2.21, 6.46±1.35 and 8.54±2.13, respectively. Significant difference in FoxP3 mRNA levels was observed among patients in different phases of CML (F =55.199, P <0.001). The expression levels of FoxP3 mRNA both in ND CML group and BP CML group were significantly higher than that in CP CML group (P <0.001), and the ND CML group was the highest (P <0.001). However, the expression levels of TGF-β in different phases of CML showed no statistical differences (H =0.634, P =0.728). The abnormal distribution of Treg subset in different phases of CML and the significant increase of the expression level of FoxP3 mRNA in the new onset and blast phase of CML suggest that Tregs may promote the occurrence and progression of CML through immune regulation.

Efficacy and safety of ponatinib in management of chronic myeloid leukaemia: Experience from Kenya.

e19067 Background: BCR-ABL tyrosine kinase inhibitors imatinib, nilotinib, bosutinib, and dasatinib, are used upfront in the management of chronic myeloid leukaemia (CML). In terms of resistance, ponatinib is the most potent tyrosine kinase inhibitor used in CML. It is however not used as first line therapy because of the fear of cardiovascular toxicity. However, because of a lot of inconsistency in the way oncology and cardiovascular trials define adverse events, this risk is not well defined. Methods: To document the efficacy and safety of ponatinib among CML patients treated at the Max Access Solutions Clinic at the Nairobi Hospital retrospectively. Results: Fourty-five patients were included between 02-10-2017 and 03-12-2022; males 23(51.1%) and females 22 (48.9%). All patients took imatinib first line. Ponatinib was taken second line by 10 (22.2%), third line by 18 (40%) and 4th line by 17 (37.8%). Of these, 25 (55.6%) were in chronic phase, 10(22.2%) accelerated and 9(20%) blastic phases. Of 22 evaluable cases in chronic phase, 1 (4.5%) died after 9 months on ponatinib, the rest are on follow-up for 1 – 60 months with a mean of 16.8 months and median of 10 months. Of 8 evaluable in accelerated phase, one (12.5%) died after 36 months. The range of follow-up is 2-36 months and mean 19.4 months. Of 9 evaluable in blastic phase, two (22.2%) are still alive after 6 and 41 months respectively. Seven (77.8%) died after follow-up ranging from 2-18 months, mean of 9.3 months. Interquartile range (IQR) for total white blood cell (wbc) count dropped from 9.08 x 109/litre to 4.82 x 109/litre on ponatinib, absolute neutrophil count dropped from 6.70 x 109/litre to 2.29 x 109/litre and platelets IQR rose from 114 x 109/litre -163 x 109/litre. Adverse events were registered in 6 (13.3 %), mainly grade 1-2, none of which was cardiovascular. Conclusions: Ponatinib is an active in all phases of CML with manageable side effect profile.

ASC2ESCALATE: A US phase 2, single-arm, dose-escalation study of asciminib monotherapy in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) previously treated with 1 prior tyrosine kinase inhibitor (TKI).

TPS7082 Background: ATP–competitive TKIs extend life expectancy in CML; yet up to 40% of newly diagnosed pts with CML-CP stop first-line (1L) therapy by 5 years due to resistance or intolerance and switch to second-line (2L) therapy. There is also an unmet need to overcome high rates of resistance in 2L. Studies show some pts with resistance achieve responses with higher doses of TKIs, while use of another second-generation (2G) TKI may not clinically benefit pts with resistance to a 2G TKI. Asciminib is the 1st BCR:ABL1 inhibitor that Specifically Targets the ABL Myristoyl Pocket (STAMP), giving it activity against most BCR:ABL1 mutations imparting resistance to ATP-competitive TKIs. Asciminib was 1st approved in the US for patients with CML-CP after ≥2 TKIs at 80 mg once daily (QD) and 40 mg twice daily (BID) and CML-CP with the T315I mutation at 200 mg BID. In the phase 3 ASCEMBL study, asciminib 40 mg BID showed superior efficacy vs bosutinib 500 mg QD in pts with CML-CP after ≥2 prior TKIs at weeks 24 (major molecular response [MMR], 25.5% vs 13.2%) and 96 (MMR, 37.6% vs 15.8%) and favorable tolerability with &gt; 2 years’ follow-up. The phase 1 dose-finding X2101 trial investigated asciminib doses of 80-200 mg QD and 10-200 mg BID; the maximum tolerated dose of asciminib was not reached and no differing safety signals were noted in patients receiving 200 mg BID vs the total treatment population. Here, we describe the phase 2 ASC2ESCALATE trial investigating efficacy and safety of 2L asciminib with dose escalation in pts with CML-CP (NCT05384587). Methods: This is a phase 2, open-label, multicenter, single-arm, dose-escalation study in the US. Adults with CML-CP without the T315I mutation with treatment resistance/failure ( BCR:ABL1IS &gt; 10% with 6-12 months of 1L treatment or &gt; 1% with &gt; 12 months of 1L treatment ) or intolerance ( BCR:ABL1IS &gt; 0.1%) with ≥6 months of treatment with 1 prior ATP-competitive TKI are eligible. All pts start treatment with asciminib 80 mg QD. For pts not achieving BCR:ABL1IS ≤1% at 6 months, dose will be escalated to 200 mg QD if pts do not have grade ≥3 or persistent grade 2 toxicity refractory to optimal management. For those without MMR at 12 months, either dose escalation from 80 to 200 mg QD or from 200 mg QD to 200 mg BID will occur or pts can be switched to an investigator’s agent of choice and taken off study treatment. Pts achieving MMR at 12 months will continue asciminib at their current dose. Pts continuing to derive clinical benefit from asciminib per investigator assessment may receive post-trial access. Recruitment for this study began August 2022 with an estimated enrollment of 92 pts with CML-CP across ≈40 sites. The primary endpoint is MMR at 12 months. Secondary endpoints include additional efficacy outcomes at 3, 6, 18, and 24 months and safety measures. Clinical trial information: NCT05384587 .

Longitudinal, prospective cardiovascular and metabolic risk in treatment-naive patients with chronic myeloid leukemia in chronic phase (CML-CP) starting tyrosine kinase inhibitor (TKI) therapy in a real-world setting.

7053 Background: Multiple TKIs used in the treatment (tx) of CML have been associated with the development of cardiovascular/metabolic (CV/Met) comorbidities, yet no study to date has prospectively and systematically assessed CV/Met parameters after TKI initiation. CA180-653 (NCT03045120) is a non-interventional, prospective, real-world study characterizing the effects of TKIs (dasatinib [DAS], imatinib [IM], nilotinib [NIL], and bosutinib [BOS]) on CV/Met risk factors in patients (pts) with CML-CP in routine care. Baseline CV/Met risks were previously reported (Mauro, GCOS 2019). Here, we report data from the final 2-year follow-up. Methods: Adult pts with newly diagnosed CML-CP due to start tx with DAS, IM, NIL, or BOS were enrolled; the BOS cohort was not analyzed independently due to small sample size. Pts were followed for 24 mo. Blood/urine samples, CV/Met assessments, coronary calcium scoring, echocardiography, and cytogenetic/molecular response assessments were collected at routine office visits at predetermined timepoints. The primary endpoint was change in CV/Met risk from baseline. Results: At the end of follow-up, 118 pts were enrolled; 49 received DAS, 47 IM, 16 NIL, and 6 BOS. Of these, 83 (70.3%) pts completed the study and 35 (29.7%) discontinued; the most common reason for discontinuation was withdrawal of consent (n = 19). No pts died from CML. At baseline, median age was 57 (range, 20–97) y; 59.3% of pts were male and 83.9% were White. Sixty-two (52.5%) pts had CV/Met risk factors at baseline, including hypertension (n = 45/62; 72.6%), hyperlipidemia (n = 33/62; 53.2%), diabetes (n = 19/62; 30.6%), and arrhythmia (n = 10/62; 16.1%). Over the study period, 1 (3.4%) patient receiving DAS and 2 (6.9%) receiving IM developed coronary artery calcification; 2 (9.1%) pts receiving IM developed pericardial effusion. Median left ventricular ejection fraction on 2D echocardiogram was normal for all TKIs at baseline (65.4% [range, 27–81]) and end of study (65.4% [range, 40–80]). Systolic and diastolic blood pressure increased from baseline only in pts who received NIL. Blood glucose levels increased from baseline for DAS, IM, and NIL (median: 1.9, 4.9, and 5.8 mg/dL, respectively), and low-density lipoprotein levels decreased from baseline in all 3 cohorts (median: 72.7, 52.1, and 56.3 U/L, respectively); data from the NIL group were limited by the small sample size. There was 1 death from myocardial infarction related to NIL. Conclusions: These findings suggest more than half of pts with CML-CP have CV/Met risk factors at baseline. At end of study, there was indication of CV/Met effects based on TKI selection. This highlights the importance of appropriate TKI selection based on pt comorbidity characteristics, along with close monitoring and management of CV/Met risks throughout tx. Clinical trial information: NCT03045120 .

Treatment-free remission after dasatinib in patients with chronic myeloid leukaemia in chronic phase with deep molecular response: Final 5-year analysis of DASFREE.

Patients with chronic myeloid leukaemia in chronic phase (CML-CP) who have a sustained deep molecular response (DMR) are eligible to discontinue treatment and attempt treatment-free remission (TFR). In the DASFREE study (ClinicalTrials.gov; NCT01850004), the 2-year TFR rate after dasatinib discontinuation was 46%; here we present the 5-year update. Patients with a stable DMR after ≥2 years of dasatinib therapy discontinued treatment and were followed for 5 years. At a minimum follow-up of 60 months, in 84 patients discontinuing dasatinib, the 5-year TFR rate was 44% (n = 37). No relapses occurred after month 39 and all evaluable patients who relapsed and restarted dasatinib (n = 46) regained a major molecular response in a median of 1.9 months. The most common adverse event during the off-treatment period was arthralgia (18%, 15/84); a total of 15 withdrawal events were reported in nine patients (11%). At the 5-year final follow-up, almost half of the patients who discontinued dasatinib after a sustained DMR maintained TFR. All evaluable patients who experienced a relapse quickly regained a DMR after restarting dasatinib, demonstrating that dasatinib discontinuation is a viable and potentially long-term option in patients with CML-CP. The safety profile is consistent with the previous report.

Low-Dose Dasatinib (50 mg Daily) Frontline Therapy in Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia: 5-Year Follow-Up Results

BackgroundDasatinib is a BCR::ABL1 tyrosine kinase inhibitor approved as frontline therapy at a 100 mg daily for chronic myeloid leukemia in chronic phase (CML-CP). The use of a lower dose of dasatinib (50 mg daily) has demonstrated better tolerance and improved outcomes compared with the standard dose. Here, we report the updated results in a large cohort with a 5-year follow-up. Patients and MethodsPatients with newly diagnosed CML-CP were eligible. Entry and response-outcome criteria were standard. Dasatinib was given as 50 mg orally daily. ResultsEighty-three patients were included. At 3 months, 78 (96%) patients achieved BCR::ABL1 transcripts (IS) ≤10%, and at 12 months, 65 (81%) patients achieved BCR::ABL1 transcript (IS) ≤0.1%. The cumulative incidence of complete cytogenetic, major molecular, and deep molecular responses at 5 years were 98%, 95%, and 82%, respectively. Rates of failures due to resistance (n = 4; 5%) and toxicity (n = 4; 5%) were low. The 5-year overall survival was 96% and event-free survival 90%. No transformations to accelerated or blastic phase were observed. Grade 3 to 4 pleural effusions developed in 2% of patients. ConclusionDasatinib 50 mg daily is an effective and safe treatment for newly diagnosed CML-CP.

Treatment after failure of frontline therapy of chronic myeloid leukemia in chronic phase including allogeneic hematopoietic stem cell transplantation.

The treatment outcomes of chronic myeloid leukemia in chronic phase (CML-CP) have dramatically improved with comparable life-expectancy to average of general population in tyrosine kinase inhibitor (TKI) era. However, less than a half of patients who started with TKI can remain on frontline TKI. The reasons of switching TKI can be either intolerance or the lack of efficacy. Although a kinase domain (KD) mutation can guide to select salvage TKI from the point of view on the efficacy of TKIs, many factors need to be considered before choosing next-line TKI such as the high-risk features of CML, the adverse events with prior TKI, and the comorbidities of patients. The therapeutic options for CML-CP after failing frontline TKI due to treatment failure or suboptimal responses will be reviewed including allogeneic hematopoietic stem cell transplantation.

Health-related quality of life of patients with resistant/intolerant chronic phase chronic myeloid leukemia treated with asciminib or bosutinib in the phase 3 ASCEMBL trial

In ASCEMBL, an open-label, randomized Phase 3 study, asciminib demonstrated superior efficacy and better safety profile compared with bosutinib in patients with chronic myeloid leukemia in chronic phase (CML-CP) previously treated with ≥2 tyrosine kinase inhibitors. Health-related quality of life (HRQOL) reported by patients is key to understanding the benefit and impact of treatment on patients’ lives, and is becoming increasingly important as the life expectancy of CML-CP patients increases and patients require long-term treatment. In ASCEMBL, patients completed questionnaires to assess CML symptoms and interference with daily life (M.D. Anderson Symptom Inventory – CML [MDASI-CML]), general HRQOL (five-level EQ-5D [EQ-5D-5L], Patient Global Impression of Change – CML [PGIC-CML]), and impact of CML on working life and activity (Work Productivity and Activity Impairment questionnaire – CML [WPAI-CML]). Patients’ CML symptoms and HRQOL remained stable during 48 weeks of treatment with asciminib, with a general trend for decreased CML symptom severity, particularly for fatigue, and improvement in HRQOL. A clinically meaningful increase in diarrhea severity was observed in patients treated with bosutinib compared to asciminib. These data provide better understanding of the patient perspective and treatment impact on HRQOL in a later-line setting, where little information has been published to date.

The m6A regulator KIAA1429 stabilizes RAB27B mRNA and promotes the progression of chronic myeloid leukemia and resistance to targeted therapy

Chronic myeloid leukemia (CML) is a common adult leukemia. Both the acute phase of the disease and the adverse effects of anti-cancer treatments can lead to a poor prognosis. The N6-methyladenine (m6A) modification plays an important regulatory role in various physiological and pathological processes. KIAA1429 is a known m6A regulator, but the biological role of KIAA1429 in CML is unclear. In this study, we observed that the m6A levels and KIAA1429 expression were significantly up-regulated in patients with blast phase CML. Notably, KIAA1429 regulated the total level of RNA m6A modification in the CML cells and promoted the malignant biological behaviors of CML cells, including proliferation, migration, and imatinib resistance. Inhibiting KIAA1429 in CML cells reduced the stability of RAB27B mRNA through the m6A/YTHDF1 axis, consequently inhibiting CML proliferation and drug efflux, ultimately increasing the sensitivity of CML cells to imatinib. Moreover, the knockdown of RAB27B also inhibited the proliferation and drug resistance of CML cells and promoted their apoptosis. Rucaparib, a recently developed anti-cancer agent, suppressed the expression of KIAA1429 and CML cell proliferation and promoted cell apoptosis. Rucaparib also inhibited the tumorigenesis of CML cells in vivo. The combined use of rucaparib and imatinib enhanced the sensitivity of CML cells to imatinib. Our study provides evidence that elevated KIAA1429 expression in the blast phase of CML enhances the stability of RAB27B mRNA through the m6A/YTHDF1 axis to up-regulate RAB27B expression, thereby promoting CML progression. Rucaparib exerts inhibitory effects on KIAA1429 expression and thus reduces CML progression.

A Case of Imatinib Induced Nephrotic Syndrome in a Child with Chronic Myeloid Leukaemia

Background:Tyrosin kinase inhibitors (TKI) are used as a targeted therapy for the treatment of chronic myeloid leukaemia and Philadelphia chromosome positive acute lymphoblastic leukaemia. Increasing use of TKI has been associated with hypertension, proteinuria and acute kidney injury. There are only afew reports of adults with TK -inhibitor associated nephrotic syndrome.But TK inhibitor associated Nephrotic syndrome is very rare in paediatric age group. Case:A -6- year old boy presented with fever, anaemia, splenomegaly, leucocytosis and finally diagnosed as accelerated phase of chronic myeloid leukaemia (CML) by bone marrow study.He achieved clinical and haematological remission with Imatinib. But developed generalized oedema and was found to have massive proteinuria and microscopic haematuria after three and half months. Renal biopsy revealed focal segmental glomerulosclerosis. Imatinib along with Prednisolone, 60 mg/m2/ day was added to treat nephrotic syndrome. Imatinib discontinued as the patient did not achieve complete remission. After one week of Imatinib withdrawal and five weeks of daily prednisolone the boy attained complete remission of nephrotic syndrome. Conclusion:Tyrosine Kinase inhibitors are important therapies in paediatric cancer and their use is expanding. Timely recognition of renal adverse effectsfor TK inhibitors can aid in the proper management of cancer patients. J Bangladesh Coll Phys Surg 2023; 41: 170-172

Blast phase of chronic myeloid leukaemia

Blast phase of chronic myeloid leukaemia

Importance of TKI treatment duration in treatment-free remission of chronic myeloid leukemia: results of the D-FREE study

Treatment-free remission (TFR) is a new goal for patients with chronic myeloid leukemia in chronic phase (CML-CP) with a sustained deep molecular response (DMR) to treatment with tyrosine kinase inhibitors (TKIs). However, optimal conditions for successful TFR in patients treated with second-generation (2G)-TKIs are not fully defined. In this D-FREE study, treatment discontinuation was attempted in newly diagnosed CML-CP patients treated with the 2G-TKI dasatinib who achieved BCR-ABL1 levels of ≤ 0.0032% (MR4.5) on the international scale (BCR-ABL1IS) and maintained these levels for exactly 1 year. Of the 173 patients who received dasatinib induction therapy for up to 2 years, 123 completed and 60 (48.8%) reached MR 4.5. Among the first 21 patients who maintained MR4.5 for 1 year and discontinued dasatinib, 17 experienced molecular relapse defined as loss of major molecular response (BCR-ABL1IS > 0.1%) confirmed once, or loss of MR4 (BCR-ABL1IS > 0.01%) confirmed on 2 consecutive assessments. The estimated molecular relapse-free survival rate was 16.7% at 12 months. This study was prematurely terminated according to the protocol’s safety monitoring criteria. The conclusion was that sustained DMR for just 1 year is insufficient for TFR in CML-CP patients receiving dasatinib for less than a total of 3 years of treatment.

Asciminib vs bosutinib in chronic-phase chronic myeloid leukemia previously treated with at least two tyrosine kinase inhibitors: longer-term follow-up of ASCEMBL

Asciminib, the first BCR::ABL1 inhibitor that Specifically Targets the ABL Myristoyl Pocket (STAMP), is approved worldwide for the treatment of adults with Philadelphia chromosome–positive chronic myeloid leukemia in chronic phase (CML-CP) treated with ≥2 prior tyrosine kinase inhibitors (TKIs). In ASCEMBL, patients with CML-CP treated with ≥2 prior TKIs were randomized (stratified by baseline major cytogenetic response [MCyR]) 2:1 to asciminib 40 mg twice daily or bosutinib 500 mg once daily. Consistent with previously published primary analysis results, after a median follow-up of 2.3 years, asciminib continued to demonstrate superior efficacy and better safety and tolerability than bosutinib. The major molecular response (MMR) rate at week 96 (key secondary endpoint) was 37.6% with asciminib vs 15.8% with bosutinib; the MMR rate difference between the arms, after adjusting for baseline MCyR, was 21.7% (95% CI, 10.53–32.95; two-sided p = 0.001). Fewer grade ≥3 adverse events (AEs) (56.4% vs 68.4%) and AEs leading to treatment discontinuation (7.7% vs 26.3%) occurred with asciminib than with bosutinib. A higher proportion of patients on asciminib than bosutinib remained on treatment and continued to derive benefit over time, supporting asciminib as a standard of care for patients with CML-CP previously treated with ≥2 TKIs.

Treatment free remission in pediatric chronic myeloid leukemia

BackgroundThe aim was to evaluate the impact of discontinuation of imatinib in children in chronic phase of chronic myeloid leukemia (CML) and assess treatment free remission (TFR). Patients and methods: We performed a retrospective study in children diagnosed with CML chronic phase up to 18 years of age, who were on imatinib for 5 years and had consistent BCR:ABL1 negative/undetectable transcripts through RT-PCR. Complete blood counts were monitored monthly and BCR:ABL1 transcripts by RT-PCR monitored 3 months. Results: Among the 14 patients who continued to remain PCR negative, we attempted discontinuing imatinib in eleven children as per the above-mentioned criteria. Eight (72%) continued to be in remission and did not require imatinib to be restarted. Among the remaining three patients, one child was noted to have increasing basophilia in the differential counts and was hence restarted on imatinib. Two other patients demonstrated recurrence of BCR:ABL1 transcript copy numbers six months after stopping TKI, following which imatinib was restarted. All three patients had documented major molecular response within three months of therapy. The median duration of TFR was 18 months in our cohort (range: 3 months–5 years). Among patients who continued to be off imatinib, TKI withdrawal symptoms were documented in 4 (36%) patients. Conclusions: Treatment free remission was achieved in 8/11 (72%) children after discontinuation of imatinib, and re-introduction of imatinib resulted in major molecular response in those with recurrence. Monitoring of BCR:ABL1 transcripts through RT PCR is essential.

Hemophagocytic Lymphohistiocytosis Appearing During Blast Phase of Chronic Myeloid Leukemia

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening illness with rapid progression and high mortality and is associated with genetic defects or can be induced by malignancies or severe infections. Most of the hematological malignancy-related HLH reported was accompanied by lymphoid neoplasms. Here, we present an unusual case of HLH with co-existing blast phase of chronic myeloid leukemia (CML-BP). A diagnosis of AML-M5 with most likely concomitant HLH was made based on the clinical features, morphology, flow cytometry immunophenotyping, and genetics. Moreover, clinical characteristics were more suggestive of myeloid blast phase CML than de novo AML with the positive p210 BCR-ABL1. However, disease-causing mutations of HLH were not available, the patient probably had secondary malignancy-associated HLH induced by an acute infection. The case focuses on the contribution of bone marrow morphological examination in getting the first diagnostic clue of CML-BP concomitant with HLH.

Olverembatinib for the treatment of chronic myeloid leukemia in chronic phase

Olverembatinib for the treatment of chronic myeloid leukemia in chronic phase

Pediatric chronic myeloid leukemia in myeloid blast crisis

Chronic myeloid leukemia (CML) accounts for 2-3% of childhood leukemias. About 5% of cases present in a blastic phase of CML which clinically and morphologically mimics more common acute leukemias of childhood. We report a case of a 3-year-old male who presented with gradual onset swelling of the abdomen and extremities along with generalized weakness. Examination revealed massive splenomegaly, pallor, and pedal edema. Initial workup showed anemia, thrombocytopenia, and leukocytosis (120,000/uL) with a blast percentage of 35%. Blasts were positive for CD13, CD33, CD117, CD34 and HLA-DR, and stained negative for Myeloperoxidase and Periodic Acid Schiff. Fluorescence in situ hybridization was positive for b3a2/e14a2 junction BCR-ABL1 transcript and negative for RUNX1-RUNX1T1/t(8;21), clinching the diagnosis of CML in myeloid blast crisis. The patient expired within 17 days of diagnosis and initiation of therapy.

Red blood cell distribution width at diagnosis as a predictor factor in chronic phase-chronic myeloid leukemia patients treated with first-generation tyrosine kinase inhibitors

BACKGROUND: Chronic myelogenous leukemia is a hematological disorder of stem cells resulting from uncontrolled and unregulated growth of myeloid cells in the bone marrow. Since the introduction of tyrosine kinase inhibitors (TKIs), therapy has dramatically improved survival in these patients. TKIs treatment targeting BCR-ABL significantly improves the prognosis of patients with chronic myelogenous leukemia. To date, the validity of scoring systems is insufficient for predicting prognosis, and there are few studies of scoring systems for predicting treatment response and clinical efficacy of TKIs. OBJECTIVES: The objective of this study was to evaluate the ability of the red blood cell distribution width (RDW) to predict treatment response in chronic myeloid leukemia-chronic phase (CP) patients treated with first-generation TKI. PATIENTS AND METHODS: A prospective and retroprospective cohort study was conducted on chronic myeloid leukemia-CP patients treated with first-generation TKI at Iraqi Hematological Centers. The collection period was from December 2020 to November 2021. Patients were treated with first-generation TKIs as initial therapy and were followed up to assess the response by polymerase chain reaction (PCR). The assessment of RDW was done at baseline and then at 3, 6, 12, and 18 months after initiation of therapy. RESULTS: There were 150 patients included in this study. The mean age of patients was 43.7 ± 14 years (range: 18–84 years). Males were representing 48.6% and females 51.3%. The classification of baseline RDW showed that the majority of patients (53%) had high RDW. The RDW showed significant change over time, in which, it was significantly decreasing over time (P &lt; 0.05). Association between PCR over time and baseline RDW category showed that the high baseline RDW was associated with higher mean PCR at 3, 6, 12, and 18 months (P &lt; 0.05). The correlation between RDW at baseline and PCR at 3, 6, 12, and 18 months showed that there was a significant positive weak correlation between baseline RDW and PCR at 6, 12, and 18 months. The association between baseline RDW and the response showed that high baseline RDW was associated with higher failure rate at 6 and 12 months (P &lt; 0.05). CONCLUSION: RDW could be used in the prediction of response to treatment. Furthermore, high RDW showed significant association with high disease activity score, high white blood cell count, and lower hemoglobin, in addition to association and correlation with PCR level.