Acta Haematologica[JOURNAL]
Sun
200 papers
Persistent COVID-19: A Case Report of an Immunocompromised Patient and a Literature Review.
Bekkaoui S, Venton G, Bretelle F … +9 more , Garrido V, Chabbert V, Gayet S, Dalmas P, Tichadou A, Jarrot PA, Villani P, Daumas A, Arcani R
Acta Haematol · 2024 · PMID 38359806 · Publisher ↗
INTRODUCTION: Immunocompromised patients can show prolonged shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and persistent symptoms, which is called persistent COVID-19. CASE PRESENTATION: We rep...
INTRODUCTION: Immunocompromised patients can show prolonged shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and persistent symptoms, which is called persistent COVID-19. CASE PRESENTATION: We report a case of an immunocompromised patient who was treated for mantle cell lymphoma and was suffering from B-cell depletion. The patient developed persistent COVID-19, which was confirmed by real-time polymerase chain reaction (RT-PCR) tests in only sputum and bronchoalveolar fluid which remained positive for at least 112 days. The patient was successfully treated with SARS-CoV-2 convalescent plasma. CONCLUSION: It could be of interest to investigate the RT-PCR results of SARS-CoV-2 in sputum/bronchoalveolar lavage samples from immunocompromised patients with unexplained pneumonia.
Lenalidomide Treatment of Isolated Central Nervous System Relapse in Acute Lymphoblastic Leukemia after Hematopoietic Stem Cell Transplantation and Chimeric Antigen Receptor T-Cell Therapy.
Zhang Q, Dong Y, Zhai Z … +2 more , Tao L, Tao Q
Acta Haematol · 2024 · PMID 38359803 · Publisher ↗
INTRODUCTION: Hematopoietic stem cell transplantation (HSCT) and chimeric antigen receptor T (CAR-T) cell are effective treatments for acute lymphoblastic leukemia (ALL). Various forms of intra- and extramedullary relaps...
INTRODUCTION: Hematopoietic stem cell transplantation (HSCT) and chimeric antigen receptor T (CAR-T) cell are effective treatments for acute lymphoblastic leukemia (ALL). Various forms of intra- and extramedullary relapses have been reported after HSCT and CAR-T-cell therapy for ALL; however, no reports have investigated isolated central nervous system (CNS) relapse after HSCT and CAR-T-cell therapy. Hence, no clinical treatment has been established for such rare patients. CASE PRESENTATION: An 18-year-old male patient with B-cell ALL suffered from isolated CNS relapse after HSCT and CAR-T-cell therapy. Conventional systemic intravenous and intrathecal chemotherapies were ineffective and intolerable. A unique immunosuppressive microenvironment of decreasing NK cell percentage and increasing IL-8 concentration and CAR-T-cell exhaustion had been illustrated in the cerebrospinal fluid. Finally, the patient received immunomodulatory therapy with lenalidomide and obtained complete remission. CONCLUSION: Lenalidomide might be a therapeutic strategy for isolated CNS relapse after HSCT and CAR-T-cell therapy.
Prevalence, Risk Factors, and Prognostic Value of Anxiety and Depression in Acute Myeloid Leukemia.
Zhong T, Xu D, Li W
Acta Haematol · 2024 · PMID 38342094 · Full text
INTRODUCTION: Limited studies report anxiety and depression prevalence and their correlations with prognosis in acute myeloid leukemia (AML). Even worse, their risk factors for AML remained unclear. This study aimed to i...
INTRODUCTION: Limited studies report anxiety and depression prevalence and their correlations with prognosis in acute myeloid leukemia (AML). Even worse, their risk factors for AML remained unclear. This study aimed to investigate the prevalence, risk factors, and prognostic value of anxiety and depression in AML patients. METHODS: Totally, 132 de novo AML patients, 60 non-malignant hematological disease patients (as disease controls), and 60 healthy controls were enrolled. Anxiety and depression status were evaluated by the Hospital Anxiety and Depression Scale (HADS) in all participants. RESULTS: HADS-anxiety score (8.2 ± 3.2 vs. 6.1 ± 2.9 vs. 4.7 ± 2.8), anxiety rate (48.5% vs. 25.0% vs. 10.0%), HADS-depression score (7.8 ± 3.0 vs. 5.8 ± 3.0 vs. 4.0 ± 2.8), and depression rate (43.2% vs. 23.3% vs. 8.3%) were highest in AML patients, followed by disease controls, and the lowest in healthy controls (all p < 0.001). Multivariate logistic regression analysis identified that factors independently associated with anxiety included male (p = 0.002, odds ratio [OR] = 0.240), smoking (p = 0.043, OR = 2.474), education duration (p = 0.024, OR = 0.889), and NCCN high-risk stratification (p = 0.008, OR = 2.347), while those independently associated with depression were age (p = 0.005, OR = 1.055), single/divorced/widowed status (p = 0.014, OR = 3.149), NCCN high-risk stratification (p = 0.002, OR = 3.077), and white blood cell (WBC) (p < 0.001, OR = 1.062). Additionally, depression was correlated with shorter accumulating event-free survival (p = 0.012) and overall survival (p = 0.041) in AML patients, whereas anxiety was not. CONCLUSIONS: Anxiety and depression are prevalent, among which depression is associated with poor survival profile, but anxiety is not; moreover, age, male, education, single/divorced/widowed status, smoking, NCCN high-risk stratification, and WBC were independent related factors of anxiety and depression in AML patients.
Multiplex Proteomics in the Identification of Potential Biomarkers of Very Severe Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease in Allogeneic Hematopoietic Cell Transplant Patients Treated with Defibrotide.
Vasudevan Nampoothiri R, Avery L, Pasic I … +3 more , Prassas I, Diamandis E, Michelis FV
Acta Haematol · 2024 · PMID 38330921 · Publisher ↗
INTRODUCTION: Despite well-established clinical criteria for diagnosis of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) following allogeneic hematopoietic cell transplantation (HCT), there is a lack of...
INTRODUCTION: Despite well-established clinical criteria for diagnosis of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) following allogeneic hematopoietic cell transplantation (HCT), there is a lack of established diagnostic protein biomarkers. METHODS: Prospective samples were collected from patients with very severe SOS/VOD at diagnosis and days +3, +7, +14, and +30 post-initiation of defibrotide. Samples from age-matched controls with no VOD were collected at days +14, +30, +60, +90, and +180 following allogeneic HCT. Serum samples were analyzed for 2,925 protein levels by antibody-based proximity extension assay (PEA). Mean differences in the log-transformed abundance values were compared using t tests in a volcano plot. RESULTS: Five patients with very severe SOS/VOD and 5 control patients were compared. Ten proteins were identified that showed a statistically significant and log-transformed 3-fold increase in concentration. They were CALCA, CCL20, GPR37, IGFBP4, IL1RL1, SLC39A14, SPINK4, FABP3, MYL3, and CHCHD10. Four different proteins, namely, CD83, leukocyte associated immunoglobulin-like receptor 2 (LAIR2), CD7, and HEM6 showed a significant decrease with defibrotide treatment. SOS/VOD resolved in 80% (n = 4) of patients, while 1 patient deceased due to SOS/VOD. CONCLUSION: PEA technology identified 10 proteins that were significantly elevated in patients with very severe SOS/VOD. Prospective studies in a larger cohort using this technology may be able to conclusively identify diagnostic protein biomarkers for SOS/VOD.
Attitudes towards COVID-19 Vaccination in Adults with Haematological Malignancies.
Blennerhassett R, Hamad N, Grech L … +12 more , Kwok A, Choi T, Forsyth C, Jagger J, Opat S, Harris S, Chan BA, Nguyen M, Bain N, Day D, Segelov E, CANVACCS Investigators
Acta Haematol · 2024 · PMID 38290477 · Full text
INTRODUCTION: Despite people with haematological malignancies being particularly vulnerable to severe COVID-19 infection and complications, vaccine hesitancy may be a barrier to optimal vaccination. This study explored a...
INTRODUCTION: Despite people with haematological malignancies being particularly vulnerable to severe COVID-19 infection and complications, vaccine hesitancy may be a barrier to optimal vaccination. This study explored attitudes towards COVID-19 vaccination in people with haematological malignancies. METHODS: People with haematological malignancies at nine Australian health services were surveyed between June and October 2021. Sociodemographic and clinical characteristics were collected. Attitudes towards COVID-19 vaccination were explored using the Oxford COVID-19 Vaccine Hesitancy Scale, the Oxford COVID-19 Vaccine Confidence and Complacency Scale, and the Disease Influenced Vaccine Acceptance Scale-Six. Open-ended comments were qualitatively analysed. RESULTS: A total of 869 people with haematological malignancies (mean age 64.2 years, 43.6% female) participated. Most participants (85.3%) reported that they had received at least one COVID-19 vaccine dose. Participants who were younger, spoke English as a non-dominant language, and had a shorter time since diagnosis were less likely to be vaccinated. Those who were female or spoke English as their non-dominant language reported greater vaccine side-effect concerns. Younger participants reported greater concerns about the vaccine impacting their treatment. CONCLUSION: People with haematological malignancies reported high vaccine uptake; however, targeted education for specific participant groups may address vaccine hesitancy concerns, given the need for COVID-19 vaccine boosters.
Prognostic Factors of Adult Hemophagocytic Lymphohistiocytosis and Clinical Utility of HLH-2004 Diagnostic Criteria and HScore: A Real-World Multicenter Study from Thailand.
Jongdee P, Julamanee J, Rattarittamrong E … +6 more , Mukura S, Wanitpongpun C, Deoisares R, Surawong A, Chajuwan T, Chanswangphuwana C
Acta Haematol · 2024 · PMID 38262370 · Publisher ↗
INTRODUCTION: Adult hemophagocytic lymphohistiocytosis (HLH) is a rare disease with a dismal prognosis. Early diagnosis and prompt management are necessary for improved outcomes. METHODS: This multicenter retrospective s...
INTRODUCTION: Adult hemophagocytic lymphohistiocytosis (HLH) is a rare disease with a dismal prognosis. Early diagnosis and prompt management are necessary for improved outcomes. METHODS: This multicenter retrospective study investigated the etiologies, survival, and prognostic factors of HLH, including the utility of HLH-2004 criteria and HScore in real-life clinical practice. RESULTS: A total of 147 HLH patients were identified by using a combination of hemophagocytosis identification in bone marrow and the HLH-related international classification disease-10. A total of 116 (78.9%) patients fulfilled the HLH diagnosis by HScore, while 91 (61.9%) patients fulfilled 5 of 8 HLH-2004 criteria. In Thailand, the clinical application of HLH-2004 criteria needed to be reduced from 8 to 6 due to a lack of sCD25 and natural killer cell activity tests. Using the adapted HLH-2004 with a cutoff value of 4 resulted in 132 (89.9%) cases meeting the diagnostic criteria. Among these 132 confirmed HLH patients by using adapted HLH-2004, HLH was triggered by infection (29.5%), autoimmune disease (12.9%), malignancy (40.9%), and unknown cause (16.7%). Median overall survival of HLH patients was extremely short (67 days). Ferritin >6,000 μg/L, HLH from infection, malignancy, and unknown etiology were demonstrated as independent prognostic factors for inferior survival (hazard ratio [HR] 2.47; 95% confidence interval [CI] 1.39-4.37, HR 4.69; 95% CI 1.38-15.92, HR 6.09; 95% CI 1.84-20.14, and HR 6.02; 95% CI 1.64-22.05, respectively). CONCLUSION: Ferritin is a helpful biomarker for HLH diagnosis and prognostic prediction. Autoimmune disease-triggered HLH has favorable outcomes. Future prospective study is required to verify the use of the adapted HLH-2004 criteria.
Outcome and Prognostic Factors of Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric Relapsed or Refractory ETV6/RUNX1-Positive Acute Lymphoblastic Leukemia.
Hu GH, Zhang XH, Liu KY … +4 more , Xu LP, Wang Y, Cheng YF, Huang XJ
Acta Haematol · 2024 · PMID 38246140 · Publisher ↗
INTRODUCTION: The role of haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HSCT) in pediatric patients with relapsed or refractory (R/R) ETV6/RUNX1-positive acute lymphoblastic leukemia (ALL) is u...
INTRODUCTION: The role of haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HSCT) in pediatric patients with relapsed or refractory (R/R) ETV6/RUNX1-positive acute lymphoblastic leukemia (ALL) is unclear. This study aimed to identify prognostic factors and explore the role of haplo-HSCT in the treatment of ETV6/RUNX1-positive ALL. METHODS: We analyzed the clinical characteristics and treatment outcomes of 20 pediatric patients who were diagnosed with ETV6/RUNX1-positive ALL and received chemotherapy/chimeric antigen receptor T-cell bridged to haplo-HSCT between 2016 and 2021 at our institution. RESULTS: With a median follow-up time of 47 months, the 3-year cumulative incidence of relapse, disease-free survival, and overall survival were 35.9% (95% confidence interval (CI): 15.3-57.1%), 59.1% (95% CI: 37.2-81.0%), and 75.0% (95% CI: 56.0-94.0%), respectively. Multivariate analysis revealed that pre-HSCT measurable residual disease (MRD) positivity (hazard ratio, 13.275; 95% CI: 2.406-73.243; p = 0.003) had a significant negative impact on relapse. A total of 7 patients experienced positive ETV6/RUNX1 gene expression at a median of 7.2 months after haplo-HSCT, and 5 of them experienced relapse at a median time of 12.1 months after haplo-HSCT. ROC curve analysis was performed to analyze the significance of pre-HSCT and post-HSCT ETV6/RUNX1 transcripts for predicting relapse; the AUC were 0.798 (95% CI: 0.567-1.0, p = 0.035) and 0.875 (95% CI: 0.690-1.0, p = 0.008), respectively. The optimal cut-off points to predict an inevitable relapse were 0.011% and 0.0019%, respectively. CONCLUSION: Patients with R/R ETV6/RUNX1-positive ALL may benefit from haplo-HSCT. Deeply eliminating pre-HSCT MRD and preemptive treatment for post-HSCT MRD may be crucial to further improving the prognosis.
Efficiency and Toxicity of Imatinib Mesylate Combined with Atorvastatin Calcium in the Treatment of Steroid-Refractory Chronic Graft-versus-Host Disease: A Single-Center, Prospective, Single-Arm, Open-Label Study.
Chen T, Li J, Wei X … +15 more , Yao H, Zhu L, Liu J, Liu Y, Wang P, Feng Y, Gao S, Liu H, Wang L, Zhao L, Gao L, Zhang C, Gao L, Zhang X, Kong P
Acta Haematol · 2024 · PMID 38232716 · Publisher ↗
INTRODUCTION: Steroid-refractory cGVHD (SR-cGVHD) presents new great challenges for treatment. We have reported that imatinib monotherapy was effective to SR-cGVHD, but the CR rate was not satisfactory and the benefit wa...
INTRODUCTION: Steroid-refractory cGVHD (SR-cGVHD) presents new great challenges for treatment. We have reported that imatinib monotherapy was effective to SR-cGVHD, but the CR rate was not satisfactory and the benefit was not showed specific to some target organs, previously. Imatinib and statin drugs have been recognized to regulate T-cell function, statins also have been demonstrated endothelia protection, but whether this combination therapy was able to improve the efficacy remains unknown. Therefore, we designed this prospective, single-arm, open-label trial to investigate the efficacy of imatinib-based combination therapy in the treatment of SR-cGVHD for the first time. METHODS: Sixty SR-cGVHD patients were entered into this trial to investigate the combination of imatinib mesylate and atorvastatin calcium for the treatment of SR-cGVHD. The primary endpoint included the overall response rate (ORR) after 6 months of combined treatment. The secondary endpoints included an evaluation of survival, changes in T-cell subsets, and adverse events. RESULTS: At baseline, 45% (27/60) of patients had moderate cGVHD, and 55.0% (33/60) of patients had severe cGVHD. At the 6-month follow-up, a clinical response was achieved in 70.0% of patients, and a complete response (CR) was achieved in 26.7%. A total of 11.7% (7/60) of patients stopped immunosuppressive therapy at this point. After 6 months of treatment, the ORR rates of the liver, skin, eyes, and oral cavity were 80.6%, 78.1%, 61.5%, and 60.9%, respectively, with the liver also having the highest CR of 58.1%. The patients with moderate cGVHD had a better CR rate than those with severe cGVHD (55.6% vs. 3.0%, p < 0.0001). The overall survival in patients with ORR was improved (p = 0.0106). Lung involvement is an independent risk factor to affected ORR achievement (p = 0.021, HR = 0.335, 95% CI: 0.133-0.847), and the dosage of steroids was reduced in ORR patients. In clinical response patients, the ratio of CD8+ T cells (p = 0.0117) and Th17 cells (p = 0.0171) decreased, while the number of Treg cells (p = 0.0147) increased after 3 months. The most common adverse events were edema, nausea, and neutropenia, which were 13.3%, 11.7%, and 11.7%, respectively. CONCLUSION: Combination treatment with imatinib mesylate and atorvastatin calcium was effective in treating SR-cGVHD and significantly decreased target organ injury, especially liver damage, indicating that T-cell regulatory function may play an important role in this process.
Pathophysiology of Acute Myeloid Leukemia.
Wachter F, Pikman Y
Acta Haematol · 2024 · PMID 38228114 · Publisher ↗
BACKGROUND: Acute myeloid leukemia (AML) is a biologically heterogenous disease arising in clonally proliferating hematopoietic stem cells. Sequential acquisition of mutations leads to expanded proliferation of clonal my...
BACKGROUND: Acute myeloid leukemia (AML) is a biologically heterogenous disease arising in clonally proliferating hematopoietic stem cells. Sequential acquisition of mutations leads to expanded proliferation of clonal myeloid progenitors and failure of differentiation, leading to fulminant AML. SUMMARY: Here, we review the pathophysiology of AML with a focus on factors predisposing to AML development, including prior chemo- and radiation therapy, environmental factors, and germline predisposition. KEY MESSAGE: Increasing genomic characterization of AML and insight into mechanisms of its development will be critical to improvement in AML prognostication and therapy.
Clinical Features of Hepatic Manifestations among Adult Patients with Hemophagocytic Lymphohistiocytosis: A Retrospective Study.
Bao Q, Xu Z, Yang F … +1 more , Lu J
Acta Haematol · 2024 · PMID 38228103 · Publisher ↗
INTRODUCTION: Liver dysfunction is common in patients with hemophagocytic lymphohistiocytosis (HLH). However, whether the severity of liver injury is associated with the prognosis of patients with HLH remains to be deter...
INTRODUCTION: Liver dysfunction is common in patients with hemophagocytic lymphohistiocytosis (HLH). However, whether the severity of liver injury is associated with the prognosis of patients with HLH remains to be determined. This study aims to assess the association of the severity of liver involvement with short-term prognosis among adult patients with HLH. METHODS: A retrospective study was performed from January 2012 to December 2020, including 150 patients with newly diagnosed HLH and liver injury. RESULTS: The majority of our cohort suffered from mild to moderate hepatic damage, presenting with Child-Turcotte-Pugh (CTP) class A (55, 36.7%) or B (74, 49.3%). The prevalence of acute liver failure (ALF) was 9.3% in our cohort. The overall 30-day mortality rate was 49.3% among the study population. HLH patients with ALF showed an extremely adverse prognosis, with a mortality rate as high as 92.9%. In a multivariate analysis, age ≥60 years (p = 0.016), blood urea nitrogen (BUN) ≥7 μmol/L (p < 0.001), and malignancy-associated HLH (p < 0.001) at the diagnosis of HLH were identified as being strongly correlated with 30-day prognosis. An excellent predictive power was found. Among the predictive scores used to assess early death of HLH patients with liver injury, the prognostic efficiency of chronic liver failure-sequential organ failure assessment (CLIF-SOFA) (AUROC: 0.936 ± 0.0211) and SOFA score (0.901 ± 0.026) were significantly better than those of the APACHE II (p < 0.001), model for end-stage liver disease score (p < 0.001) and CTP scores (p < 0.001). CONCLUSION: Patients with old age, elevated BUN, and malignancy had inferior survival. CLIF-SOFA and SOFA enable more accurate prediction of early death in HLH patients with liver injury than other liver-specific and general prognostic models.
Successful Treatment with Daratumumab of a Patient with Monoclonal Lambda Light Chain Disease Presenting as Nephrotic Syndrome and Crescentic Glomerulonephritis.
Bnaya A, Ganzel C, Shavit L
Acta Haematol · 2024 · PMID 38228095 · Full text
INTRODUCTION: Monoclonal immunoglobulin deposition diseases (MIDDs) are a group of systemic diseases, characterized by deposition of monoclonal immunoglobulin predominantly in the kidney. In the absence of overt hematolo...
INTRODUCTION: Monoclonal immunoglobulin deposition diseases (MIDDs) are a group of systemic diseases, characterized by deposition of monoclonal immunoglobulin predominantly in the kidney. In the absence of overt hematologic disease, MIDDs are classified as a part of monoclonal gammopathy of renal significance. Patients with MIDD may present with a nephrotic syndrome and kidney function impairment. Treatment usually includes anti-plasma cell therapy. CASE PRESENTATION: We report a case of a 54-year-old female who presented with nephrotic syndrome related to light chain deposition disease of lambda type. Due to a complicated clinical course (including cardiac injury and thromboembolic stroke), plasma cell-targeted therapy was stopped. A few months later, the patient presented with severe acute kidney injury. Kidney biopsy revealed crescentic glomerulonephritis, and immunofluorescence staining was positive for lambda chain. Treatment with daratumumab was initiated resulting in stabilization of kidney function and partial nephrotic syndrome remission. CONCLUSION: This case highlights an uncommon histologic manifestation in a patient diagnosed with light chain deposition disease. Furthermore, it underscores the significance of plasma cell-targeted therapy and the favorable clinical and hematological response observed with daratumumab.
Health-Related Complications during Follow-Up and Their Impact on Blood Cancer Survivors: Results from the "Aftercare in Blood Cancer Survivors" (ABC) Study.
Baum J, Lax H, Lehmann N … +4 more , Merkel-Jens A, Beelen DW, Jöckel KH, Dührsen U
Acta Haematol · 2024 · PMID 38228094 · Publisher ↗
INTRODUCTION: Blood cancer survivors are at increased risk for medical complications. METHODS: Our questionnaire-based study involved 1,551 blood cancer survivors with a ≥3-year interval since the last intense treatment....
INTRODUCTION: Blood cancer survivors are at increased risk for medical complications. METHODS: Our questionnaire-based study involved 1,551 blood cancer survivors with a ≥3-year interval since the last intense treatment. Its goal was to quantify health-related complications during follow-up and assess their impact on the patients' lives. RESULTS: A total of 20.4% of the responding survivors reported a disease relapse, most often in indolent lymphomas. Second primary malignancies occurred in 14.1%, primarily in lymphoma and allogeneic transplantation survivors. The most frequent malignancy was basal cell carcinoma of the skin, but myeloid malignancies, melanoma, bladder, head-and-neck, and thyroid cancer also appeared disproportionately frequent. An increased infection rate was reported by 43.7%, most often after allogeneic transplantation. New cardiovascular diseases were reported by 30.2%, with a high rate of thromboembolic events in multiple myeloma (MM) and myeloproliferative diseases. Polyneuropathies were reported by 39.1%, most often by survivors with a history of MM or aggressive lymphoma. Disease relapse was perceived as the highest burden, followed by second primary malignancy, increased infection frequency, and polyneuropathy. In each area investigated, the range of perceived severities was wide. CONCLUSIONS: Health-related complications are frequent during blood cancer follow-up, with significant repercussions on the patients' lives.
Unusual Clinical Presentations of Hairy Cell Leukemia.
Troussard X
Acta Haematol · 2024 · PMID 38176393 · Publisher ↗
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BCR::ABL1-Like B-Cell Acute Lymphoblastic Leukemia with BCR::PDGFRA Fusion: A Case Report and Literature Review.
Hua J, Yan H, Qian X … +8 more , Gao D, Yang B, Xu Y, Li J, Weng X, Zhu Y, Mi JQ, Wang J
Acta Haematol · 2024 · PMID 41143846 · Publisher ↗
INTRODUCTION: We report a case of B-cell acute lymphoblastic leukemia (B-ALL) involving the breakpoint cluster region (BCR) and platelet-derived growth factor receptor alpha (PDGFRA) (BCR::PDGFRA) fusion gene, classified...
INTRODUCTION: We report a case of B-cell acute lymphoblastic leukemia (B-ALL) involving the breakpoint cluster region (BCR) and platelet-derived growth factor receptor alpha (PDGFRA) (BCR::PDGFRA) fusion gene, classified as a BCR::ABL1-like subtype. To our knowledge, this is the first such report. CASE PRESENTATION: The patient tested negative for BCR::ABL1 fusion. t(4;22)(q12;q11.2) was detected by karyotype analysis. BCR::PDGFRA transcripts were detected by RNA sequencing. Dasatinib combined with chemotherapy was ineffective. Furthermore, EZH2 mutation was detected. Imatinib, which led to complete remission, was administered; flow cytometry revealed that the minimal residual disease had dropped to 0.008%, and RT-qPCR revealed that BCR::PDGFRA/ABL1 dropped to 9.18 × 10-4. CONCLUSION: It is noteworthy that imatinib was more effective than dasatinib in our case, although the duration of remission was short. Our findings suggest that other therapies like allogeneic hematopoietic stem cell transplantation may need to be combined to improve long-term survival in ALL cases with BCR::PDGFRA.
Treatment Outcomes of Acute Myeloid Leukemia in Patients Living with Human Immunodeficiency Virus Receiving Antiretroviral Therapy: A Single-Center Experience.
Tinajero J, Ngo D, Puing A … +1 more , Koller P
Acta Haematol · 2023 · PMID 38156364 · Publisher ↗
Patients living with HIV are now living longer due to increased access to antiretroviral therapy (ART) and a decrease in acquired immunodeficiency syndrome-defining cancer (ADC). However, increasing age and previous chem...
Patients living with HIV are now living longer due to increased access to antiretroviral therapy (ART) and a decrease in acquired immunodeficiency syndrome-defining cancer (ADC). However, increasing age and previous chemotherapy exposure for ADC (e.g., anthracyclines and topoisomerase inhibitors) are factors that may increase the risk of developing therapy-related myelodysplastic syndrome and acute myeloid leukemia (AML) and highlight an unmet need. There are no established guidelines for the treatment of AML in patients with HIV and the literature is limited to treatment outcomes and experience. In addition, cladribine, a purine analog used in AML, has a package insert warning to avoid administration with concurrent agents that undergo phosphorylation, which include HIV ART backbones (e.g., nucleoside reverse transcriptase inhibitors [NRTI]). Whether concurrent NRTI-based ART is deliverable with AML induction chemotherapy has not been reported previously. In our single-center experience of seven HIV-AML patients, all patients continued concurrent ART with induction chemotherapy. In 6 evaluable patients, three (50%) of patients went into complete remission (CR). Five (71.4%) patients were able to proceed to allogenic hematopoietic stem cell transplantation (HCT). Median OS was 16.6 months, with patients who received HCT having longer median OS compared to those who were unable to proceed to HCT (49.6 months vs. 3.4 months). Interestingly, none of the patients who received AML regimens that included fludarabine were able to obtain a response. On the contrary, 4 patients who received AML regimens that utilized cytarabine given over a prolonged period of time (e.g., 7 + 3, liposomal daunorubicin/cytarabine) achieved a CR rate of 75%. Concurrent HIV ART and AML induction chemotherapy is deliverable, although much remains to be investigated on potential drug interactions between purine analog-based chemotherapy and HIV ART.
The Effect of Oral Iron Chelator Deferiprone on Iron Overload and Oxidative Stress in Patients with Myelodysplastic Syndromes: A Study by the Israeli MDS Working Group.
Merkel D, Soffer S, Filanovsky K … +8 more , Braester A, Fibach E, Dana M, Ofran Y, Greenbaum U, Nagler A, Amitai I, Mittelman M
Acta Haematol · 2024 · PMID 38104534 · Full text
BACKGROUND: Most patients with lower risk myelodysplastic neoplasms or syndromes (MDSs) become RBC transfusion-dependent, resulting in iron overload, which is associated with an increased oxidative stress state. Iron-che...
BACKGROUND: Most patients with lower risk myelodysplastic neoplasms or syndromes (MDSs) become RBC transfusion-dependent, resulting in iron overload, which is associated with an increased oxidative stress state. Iron-chelation therapy is applied to attenuate the toxic effects of this state. Deferiprone (DFP) is an oral iron chelator, which is not commonly used in this patient population, due to safety concerns, mainly agranulocytosis. The purpose of this study was to assess the effect of DFP, on oxidative stress parameters in iron-overloaded RBC transfusion-dependent patients with lower risk MDSs. METHODS: Adult lower risk MDS patients with a cumulative transfusion burden of >20 red blood cell units and evidence of iron overload (serum ferritin >1,000 ng/mL) were included in this study. DFP was administered (100 mg/kg/day) for 4 months. Blood samples for oxidative stress parameters and iron overload parameters were done at baseline and monthly: reactive oxygen species (ROS), phosphatidylserine, reduced glutathione, membrane lipid peroxidation, serum ferritin, and cellular labile iron pool. The primary efficacy variable was ROS. Tolerability and side effects were recorded as well. A paired t test was applied for statistical analyses. RESULTS: Eighteen patients were treated with DFP. ROS significantly decreased in all cell lineages: median decrease of 58.6% in RBC, 33.3% in PMN, and 39.8% in platelets (p < 0.01 for all). Other oxidative stress markers improved: phosphatidylserine decreased by 57.95%, lipid peroxidase decreased by 141.3%, and reduced gluthathione increased by 72.8% (p < 0.01 for all). The iron-overload marker and cellular labile iron pool decreased by 35% in RBCs, 44.3% in PMN, and 46.3% in platelets (p < 0.01 for all). No significant changes were observed in SF levels. There were no events of agranulocytosis. All AEs were grades 1-2. CONCLUSIONS: Herein, we showed preliminary evidence that DFP decreases iron-induced oxidative stress in MDS patients with a good tolerability profile (albeit a short follow-up period). No cases of severe neutropenia or agranulocytosis were reported. The future challenge is to prove that reduction in iron toxicity will eventually be translated into a clinically meaningful improvement.
Diagnostic Precision or Pitfalls: How to Apply the New Acute Myeloid Leukemia Classification Systems?
Carlson KS, Cunningham A, Stahl M … +2 more , Winer E, Michaelis LC
Acta Haematol · 2024 · PMID 38071966 · Publisher ↗
BACKGROUND: The classification of acute myeloid leukemia (AML) has long been overseen by the World Health Organization (WHO) and published into a series of "Blue Books." These ledgers serve as the reference manual for AM...
BACKGROUND: The classification of acute myeloid leukemia (AML) has long been overseen by the World Health Organization (WHO) and published into a series of "Blue Books." These ledgers serve as the reference manual for AML classification and, in turn, classification-based treatment decisions. In 2022, two separate groups, each of which included hematologic oncologists, hematopathologists, and geneticists - developed and published two parallel classification systems for AML. One is from the WHO (WHO 5th edition), and a second is from an International Advisory Consortium (International Consortium Classification [ICC]). SUMMARY: Both modern classification systems originated from the revised 4th edition of the WHO Blue Books and thus share many similarities. There are never-the-less several important differences with the potential to substantially alter disease classification, access to clinical trials, and treatment decision-making. In this manuscript, we review the organization of the WHO and ICC classification systems for AML with emphasis on their similarities and differences, followed by areas in which their application to clinical scenarios may present difficulties. KEY MESSAGES: (1) The ICC and WHO 5th edition are concordant for the majority of AMLs. (2) Key differences between AML classification by the ICC and WHO 5th edition include (a) the overall framework of classification, (b) AML-defining blast threshold, definition of myelodysplasia-related AML, and (c) strategy for assigning therapy-related or germline-associated AML modifiers.
Strategies to Mitigate the Drug-Drug Interaction between Nirmatrelvir/Ritonavir and Tacrolimus in Allogeneic Hematopoietic Stem Cell Transplant Recipients on Azole Antifungals: Results of a Case Series.
Griffin SP, Lee B, Doh J … +10 more , Paradyse AR, Jeyakumar D, Arter Z, Nam H, Blodget E, Smith J, Valek A, Vittayawacharin P, Kongtim P, Ciurea SO
Acta Haematol · 2023 Oct · PMID 38059378 · Publisher ↗
INTRODUCTION: Nirmatrelvir/ritonavir (NIM/r) inhibits tacrolimus metabolism resulting in a profound drug-drug interaction that is further complicated by the use of azole antifungals. CASE PRESENTATIONS: We describe three...
INTRODUCTION: Nirmatrelvir/ritonavir (NIM/r) inhibits tacrolimus metabolism resulting in a profound drug-drug interaction that is further complicated by the use of azole antifungals. CASE PRESENTATIONS: We describe three strategies, in 4 patient cases, for the initiation of NIM/r in allogeneic hematopoietic stem cell transplant (alloHSCT) recipients on tacrolimus at the time of diagnosis. Patients 1 and 2 (strategy 1) experienced prolonged, elevated tacrolimus concentrations after an empiric 33% reduction in tacrolimus dose and adjustment of azole antifungal at NIM/r initiation (strategy 1) and with complete discontinuation of tacrolimus and azole antifungal at NIM/r initiation (strategy 2). Patients 3 and 4 (strategy 3) did not experience elevated tacrolimus concentrations on NIM/r treatment with complete discontinuation of tacrolimus and azole antifungal and a 12-24-h delay in NIM/r initiation. Reinitiation of tacrolimus after NIM/r completion resulted in variable tacrolimus concentrations. CONCLUSION: NIM/r-tacrolimus is a serious drug-drug interaction which can be mitigated by early discontinuation of tacrolimus and azole antifungals, close monitoring, and reinitiation of tacrolimus and antifungal 48-72 h after completion of therapy.
TP53-Mutated Myelodysplastic Syndrome and Acute Myeloid Leukemia: Current Guidelines, Therapies, and Future Considerations.
DiGennaro J, Sallman DA
Acta Haematol · 2024 · PMID 38052186 · Publisher ↗
BACKGROUND: Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy characterized by uncontrolled proliferation and impaired differentiation of myeloid cells in the bone marrow. The tumor suppressor gene...
BACKGROUND: Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy characterized by uncontrolled proliferation and impaired differentiation of myeloid cells in the bone marrow. The tumor suppressor gene TP53 plays a crucial role in maintaining genomic integrity and preventing the development of cancer. TP53 mutations are frequently observed in AML (∼10% of patients) and are associated with aggressive disease behavior, resistance to therapy, and poor prognosis. SUMMARY: Recent changes in classification of TP53-mutated myelodysplastic syndrome (MDS) have occurred related to the allelic status of TP53 and more importantly to harmonize MDS/AML patients as a homogeneous hematological malignancy. Current treatment regimens involve hypomethylating agents +/- venetoclax or intensive chemotherapy although unfortunately independent of treatment regimen the overall survival (OS) of this patient cohort is around 6 months with poor long-term outcomes after allogeneic stem-cell transplantation. Recent developments geared toward the treatment of TP53-mutated MDS/AML have focused on immunotherapies. KEY MESSAGES: Notably, there is optimism surrounding these new therapies that could provide breakthroughs with improving outcomes either as monotherapy or combined with established nonimmune therapies. This paper aims to provide an overview of TP53-mutated MDS/AML, including the underlying mechanisms, clinical implications, and emerging therapeutic strategies targeting this hematologic malignancy.
Geriatric Assessment in Acute Myeloid Leukemia.
Woods JD, Klepin HD
Acta Haematol · 2024 · PMID 38035561 · Full text
BACKGROUND: Acute myeloid leukemia (AML) is a heterogenous disease that affects mostly older adults with varying baseline health and functional status. Treatment options have expanded for older adults, ranging from less...
BACKGROUND: Acute myeloid leukemia (AML) is a heterogenous disease that affects mostly older adults with varying baseline health and functional status. Treatment options have expanded for older adults, ranging from less intensive chronic therapies to intensive induction strategies with curative intent. Despite this, outcomes remain poor with advancing age due to underlying disease biology and variability in treatment tolerance. Reliance on chronological age alone, however, increases risks of both over- and under-treatment. Strategies to better characterize fitness in the context of therapy are needed to optimize decision-making and enhance clinical trial design. SUMMARY: Geriatric assessment (GA) is a series of validated tools that evaluate multiple health and functional domains of an older adult including physical function, comorbidities, cognition, nutrition, psychological health, and social support. While studies of GA in AML remain limited, current evidence shows that it is feasible to perform GA among older adults starting therapy for AML. GA measures including those assessing physical function, cognition, and mood are associated with mortality and toxicity in both intensive and less intensive treatment settings. KEY MESSAGES: In this review, we discuss the existing evidence to support use of GA in AML and highlight implications for clinical practice and future research.
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