Secondary pure red cell aplasia (PRCA) is one of the most common cytopenic complications in T-cell large granular lymphocyte (T-LGL) leukemia and requires therapeutic intervention. Refractory T-LGL-associated PRCA lacks a unified salvage regimen, and effective targeted agents remain scarce. In recent years, epigenetic modifications have been implicated in the pathogenesis of T-LGL leukemia, yet relevant clinical evidence is limited. We report a case of refractory T-LGL leukemia complicated by PRCA that was resistant to cyclosporine (CsA). Then the patient achieved rapid disease control with chidamide plus thalidomide in the early phase, and has maintained long-term remission for six years on chidamide monotherapy after thalidomide discontinuation. Notably, clonal T-cell receptor (TCR) variable β-chain (Vβ) 3 persisted on flow cytometry throughout the treatment course. As an epigenetic modulator, chidamide represents a more convenient and promising therapeutic strategy for managing T-LGL leukemia, prompting us to present this case.
The immune checkpoints programmed death-ligand (PD-L)1 and PD-L2 are expressed in follicular lymphoma (FL), yet immune checkpoint blocking antibodies have failed in FL. We previously initiated a phase I immune modulating vaccination (IMV) trial targeting PD-L1 and PD-L2 in patients with advanced follicular lymphoma. The study suggested a clinical effect of the vaccine, however due to relatively short follow-up time and a heterogeneous patient population no clear conclusions could be made after the trial. In this study we present follow-up data on the eight patients included in the trial. Notably, two patients displayed an unusual disease history after completion of the vaccination trial. One patient had experienced two relapses at two years after diagnosis, then received vaccines after third line therapy and subsequently remained treatment-free for five years after vaccinations. The other patient who entered the vaccine trial after third line therapy remains in complete response at 6.5 years after the vaccination trial. Longitudinal immune monitoring in these two patients demonstrated persistent, functionally active vaccine-specific CD4⁺ and CD8⁺ T-cell responses years after vaccine completion. These results suggest a disease modifying effect of targeting PD-L1 and PD-L2 by IMV in FL. Trial registration number: NCT03381768. Date of registration: December 22, 2017.
Mixed phenotype acute leukemia (MPAL) is a rare, heterogeneous group of acute leukemias of ambiguous lineage (2-5% of cases) with no consensus treatment. We retrospectively reviewed all patients with MPAL managed in a single Tunisian hematology department between January 2014 and December 2023. Diagnosis relied on multiparameter flow-cytometric immunophenotyping using the EGIL score and the WHO classifications; survival was estimated by the Kaplan-Meier method. Thirteen patients were included (median age 23 years, range 2-46; sex ratio ≈ 1.1). Twelve had a B/myeloid and one a T/myeloid phenotype; on cross-classification, 11 of the 13 EGIL-defined cases also fulfilled the stricter WHO criteria. Cytogenetic abnormalities were found in 10 patients, including t(9;22) in two and a complex karyotype in three. Eleven patients received an ALL-type induction, with a tyrosine kinase inhibitor in BCR-ABL1-positive disease; complete remission was obtained in 9 of 11 evaluable patients, and two underwent allogeneic stem-cell transplantation. Treatment-related mortality was high (53.8%), mainly infectious, and median overall survival was 19.2 months (1- and 5-year overall survival 54% and 30.8%). This series, one of the first dedicated cohorts from Tunisia, confirms the rarity and severity of MPAL and supports precise diagnosis, individualized multidisciplinary management, and multicenter collaboration.
Background:Juvenile myelomonocytic leukemia (JMML) rarely manifests with extramedullary involvement beyond spleen, liver, or skin; testicular infiltration at diagnosis is unreported. We describe a Novel Case of bilateral testicular leukemic infiltration as the initial presentation of NRAS-mutant JMML in a toddler, with rapid remission following azacitidine bridging and haploidentical HSCT. Case presentation:A 2-year-old boy presented with pallor, abdominal distension, and bilateral scrotal swelling. Labs: leukocytosis (58 × 10⁹/L, monocytes 12.8 × 10⁹/L), anemia (Hb 8.2 g/dL), HbF 22%. BM confirmed JMML with NRAS p.G12D (VAF 42%). No pathogenic variants were detected in KRAS, PTPN11, CBL, or NF1. Conventional cytogenetic analysis demonstrated a normal male karyotype (46,XY). US: testes enlarged (18.8/18.2 mL) with hypoechoic infiltration. Azacitidine (75 mg/m²/d × 5, 2 cycles) reduced counts and size. Paternal haplo-HSCT (Flu-Treo-TT conditioning, PTCy) engrafted D + 18; testes normal at 6 weeks, molecular remission (NRAS-) at 3 months. Conclusions:This novel case underscores the efficacy of azacitidine and haploidentical HSCT for NRAS-mutant JMML with testicular involvement. Routine genital examination and ultrasound are recommended for male patients.
Blinatumomab, a CD3/CD19 bispecific T-cell engager, improves outcomes in adult B-cell acute lymphoblastic leukemia (B-ALL), but CD19-negative relapse is an important mode of treatment failure. We report a 69-year-old woman with Philadelphia chromosome-negative B-ALL who achieved hematological complete remission after hyper-CVAD induction therapy but remained measurable residual disease (MRD)-positive. Blinatumomab was administered after one cycle of high-dose methotrexate/cytarabine, resulting in MRD negativity after one cycle. However, blinatumomab was discontinued after one cycle at the patient's request, and hematological relapse occurred three months after MRD conversion. Relapsed blasts showed selective loss of CD19 expression, whereas cytoplasmic CD22 expression was retained. G-banding showed an apparent cytogenetic shift from a diagnostic hyperdiploid abnormal karyotype to a normal karyotype at first relapse. Inotuzumab ozogamicin induced a second hematological remission with MRD negativity, although disease control was not durable. This case highlights the importance of repeat immunophenotypic and cytogenetic assessment at relapse after blinatumomab treatment.
CD19 directed immunotherapy with monoclonal antibodies and chimeric antigen receptor T (CAR-T) cell therapy has shown treatment efficacy in the relapsed/refractory setting for non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL). However, the CD19 directed bispecific T-cell engager, blinatumomab, is currently only approved in B-cell acute lymphoblastic leukemia (ALL) and has largely not been investigated in other clinical contexts for CLL. We report a case of a patient who presented with both Philadelphia chromosome positive (pH+) ALL and CLL who achieved measurable residual disease (MRD) negative remission for both diseases with blinatumomab.
Central nervous system (CNS) involvement in chronic lymphocytic leukemia (CLL) is rare and presents major diagnostic and therapeutic challenges. We report the case of a man in his late 40s with small lymphocytic leukemia, initially managed conservatively, who presented after four years with progressive left facial numbness, diplopia, and left oculomotor nerve palsy without B symptoms or raised intracranial pressure. He had high-risk disease biology with TP53 mutation and unmutated IGHV status. Positron emission tomography-computed tomography showed mildly FDG-avid systemic lymphadenopathy but intensely avid thickened spinal nerve roots, while magnetic resonance imaging demonstrated enhancement of the bilateral oculomotor nerves, left optic nerve, and extradural tissue at the cervical level. Cerebrospinal fluid analysis showed elevated protein and 34% abnormal B-lymphoid cells with a CLL phenotype. Biopsy of the involved nerve/root tissue confirmed direct CNS and nerve-root infiltration by CLL rather than Richter transformation. The patient was treated with acalabrutinib, venetoclax, obinutuzumab, and intrathecal chemotherapy. He showed rapid neurological improvement, with early symptom resolution, progressive cerebrospinal fluid clearance, and near-complete radiologic response, followed by complete metabolic response on follow-up PET-CT. This case highlights that CNS involvement may occur even in treatment-naïve or early-stage CLL and may not correlate with systemic disease burden. It also supports the clinical activity of novel triplet CNS-penetrant targeted agents, in achieving durable remission in rare CNS manifestations of high-risk CLL.
Hodgkin's lymphoma is a malignancy of lymphoid tissue with a generally favorable prognosis; however, symptomatic initial presentation with pericardial involvement is rare and presents significant diagnostic and therapeutic challenges. We report the case of a previously healthy 17-year-old male who presented with a four-month history of progressive cough and exertional dyspnea, along with a newly noticed right supraclavicular mass, without systemic B symptoms. Transthoracic echocardiography demonstrated a mild pericardial effusion, and subsequent PET-CT imaging revealed findings consistent with advanced disease. An excisional biopsy of the lymph node confirmed the diagnosis of nodular sclerosis classical Hodgkin lymphoma, and the patient was staged as Stage IV due to both pulmonary and pericardial involvement. Initial cytoreductive treatment with COP (Cyclophosphamide, Vincristine, Prednisone) was administered, followed by standard ABVD (Adriamycin, Bleomycin, Vinblastine, Dacarbazine) chemotherapy. This case illustrates the importance of including lymphoproliferative disorders in the differential diagnosis of pericardial effusion. Furthermore, it emphasizes the importance of early imaging, histopathological confirmation, and a multidisciplinary approach in guiding appropriate treatment strategies. As this can help prevent severe complications and enhance the patient's prognosis.
Managing acute leukemia during pregnancy poses clinical challenges requiring a balance between maternal treatment and fetal preservation. From 2019 to 2024, 22 pregnant women were diagnosed with acute leukemia, including 7 acute lymphoblastic leukemia, 15 cases of acute myeloid leukemia, of which 1 was acute promyelocytic leukemia. Diagnosis occurred in the first, second, and third trimesters in 5, 10, and 7 patients, respectively. Nine patients elected pregnancy termination, one had a spontaneous abortion, one had intrauterine fetal demise, and three experienced concurrent maternal and fetal death. Eight patients delivered via elective cesarean section, including one twin pregnancy, resulting in 9 live births. Four neonates (including one twin pregnancy) were exposed to in utero chemotherapy, with no observed congenital anomalies. Chemotherapy was administered to 11 patients, including 3 during pregnancy, all achieving temporary disease control. These findings provide real-world data to inform the management of acute leukemia during pregnancy.
Background: The immunoglobulin (IG) gene rearrangements provide valuable markers in monitoring minimal residual disease (MRD) after treatment in multiple myeloma (MM) patients. Methods: We conducted an observational study from June 2019 to June 2023. Bone marrow samples from newly diagnosed MM patients at Blood Transfusion Hematology Hospital were collected and analyzed for IG gene rearrangements. Clonal IG gene rearrangement samples were analyzed for the repertoire of rearrangements. Results: 111 newly diagnosed MM patients were collected. Bone lesions and anemia were found in 100% and 77.5% of patients, respectively. According to rISS classification, 91.9% of patients were diagnosed at an advanced stage. Cytogenetic analysis showed that 28.8% of patients expressed at least one high-risk abnormality. The most common immunophenotype of malignant plasma cells was CD38+CD138+CD19-CD56+. Noteworthily, 104 patients (93.7%) expressed at least one clonal IG gene rearrangement, while 69.4% and 18.9% of patients expressed double and triple IG gene rearrangements, respectively. VH3 and VH4 were the two most frequent among VH segments, while DH3 and JH4 were the most common among DH and JH segments, and VK1 and JK4 were the most popular repertoires in IGK gene rearrangements. KDE rearrangements were detected in 42.5% patients, and VL1 and JL3 were the most common segments in IGL gene rearrangements. Notably, the rate of clonal IGH gene rearrangements was significantly different between heavy-chain and light-chain only MM groups. Conclusion: This is the first study in Vietnamese MM patients to comprehensively describe the characteristics of IG gene rearrangements.
Factor X deficiency is a very rare coagulopathy caused by a constitutional or acquired deficiency of factor X, or by the presence of a circulating anticoagulant in the blood. Factor X deficiency has already been described in patients with AL amyloidosis, the pathophysiological mechanism being related to factor X trapping in amyloid deposits. We report the case of a patient with multiple myeloma and acquired factor X deficiency, in whom the diagnosis of amyloidosis was excluded by all investigations. Factor X deficiency is exceptionally reported in the context of multiple myeloma, where the deficiency is related to plasma cell dyscrasia responsible for the production of monocolonal immunoglobulins of the light chain type. This case report reviews the procedures to be followed by clinicians and biologists in multiple myeloma hemopathy, and systematically includes a hemostasis work-up in the initial management of the disease. Acquired factor X deficiency can cause life-threatening bleeding if not properly managed.
Objective Hematopoietic stem cell transplantation (HSCT) is an effective treatment for acute myeloid leukemia (AML) patients, leveraging cytotoxic conditioning regimens and graft-versus-leukemia effects. Reduced-intensity conditioning (RIC) regimens extend this therapy to elderly patients and those with severe comorbidities, minimizing toxicity while maintaining efficacy. The study aims to determine the result of reduced-intensity conditioning regimens for acute myeloid leukemia patients at Blood Transfusion Hematology Hospital, Vietnam. Methods The retrospective observational study included 21 AML patients who underwent RIC from January 2021 to March 2024. Results Median recovery times for neutropenia and thrombocytopenia were 16 and 26 days, respectively. Complications included mucositis (95.2%), febrile episodes (85.7%), CMV reactivation (83.3%), acute GVHD (23.8%), and chronic GVHD (14.3%). The 2-year disease-free survival (DFS) and overall survival (OS) rates were 61.4% and 69.3%, respectively. Conclusions Reduced-intensity conditioning regimens are a safe and effective treatment option for elderly AML patients with comorbidities.
This case report examines three patients with relapsed/refractory FLT3-ITD+ acute myeloid leukemia (AML) treated with FLT3 inhibitors (FLT3i) and venetoclax (VEN). While the combination therapy showed promising antileukemic activity, all patients experienced severe myelosuppression, leading to treatment interruptions. Two patients died following disease progression after therapy discontinuation, while one maintained remission with an alternating treatment schedule. These cases highlight the importance of minimizing treatment interruptions while balancing infection risks and suggest that combination or sequential therapy with VEN and FLT3i may be effective for relapsed/refractory (R/R) FLT3-ITD+ AML when treatment duration and dosing are properly managed.
We report a case of a 25-year-old male with recurrent oral ulcers, upper respiratory tract infections, and an 8-year history of chronic neutropenia. Previously diagnosed with Behçet's disease, the patient had undergone comprehensive hematological evaluations at multiple tertiary institutions, yet the etiology of his persistent neutropenia remained undetermined. Whole-exome sequencing revealed a TLR8-G572D mutation, leading to a diagnosis of autoimmune myelofibrosis (AIMF) secondary to TLR8 gain-of-function (GOF). While concurrent Behçet's disease and neutropenia may occur clinically, the underlying pathogenesis is often neglected. TLR8-GOF screening should be emphasized in young patients with such presentations. To our knowledge, this is the first reported association between TLR8-GOF mutation and AIMF, expanding the phenotypic spectrum of TLR8-related disorders.
Objective: Second generation tyrosine kinase inhibitors (TKIs) such as gilteritinib, characterized by minimal EGFR and absent VEGFR inhibition, are in theory associated with low dermatologic toxicity. This case report brings to the awareness that the opposite may occur and emphasize the need for attentive pharmacovigilance.Methods: An elderly woman presented to us with relapsed/refractory (R/R) FLT3-ITD AML following azacytidine treatment, received single-agent TKI gilteritinib, selected for its greater potency and specificity. Unexpectedly, she developed a severe hand-foot skin lesion requiring treatment interruption.Results: After receiving two cycles of gilteritinib 120mg orally daily without therapeutic response, the dose was escalated to 200mg in accordance with RCT guidelines. After one week, the patient developed dry skin and mild erythema of the hands and feet, which progressed to a severe hand-foot syndrome the following week.Conclusion: This unprecedented adverse event reporting suggests that the FLT3-specific TKI gilteritinib can induce cutaneous toxicities, through dose-dependent inhibition of proangiogenic pathways.
Background Relapsed or refractory classical Hodgkin lymphoma (R/R cHL) remains challenging, and achieving metabolic complete response prior to autologous stem cell transplantation (ASCT) is important. GDP is a generally well-tolerated outpatient regimen, while brentuximab vedotin (BV) has demonstrated encouraging activity in salvage combinations. Adult real-world data on BV+GDP remain limited. Methods Eight adult R/R cHL patients received BV+GDP between May 2023 and March 2025. Responses (Lugano 2014), toxicities (CTCAE v5.0), and mobilization outcomes were retrospectively evaluated. Results Complete response was achieved in 7/8 patients (87.5%). All responders underwent successful stem-cell mobilization and ASCT. Toxicities were manageable, with no febrile neutropenia or renal toxicity observed. At a median follow-up of 10.6 months, all patients remained alive and progression-free. Conclusion BV+GDP showed encouraging activity with acceptable tolerability, supporting further prospective evaluation.
Background The interplay between JAK2 mutation, thrombosis, and the baseline clinical and hematologic profile of MPN remains poorly understood. This study aims to provide insight on the relationship between the clinical profile and hematologic findings, JAK2 V617F mutation, and the occurrence of thrombotic events in BCR-ABL1 negative MPNs. Materials and Methods We retrospectively analyzed 198 patients with BCR-ABL1-negative MPNs to assess associations between JAK2 V617F mutation status, hematologic parameters, clinical features, and thrombotic events. Results Patients under 40 years old were associated with JAK2 V617F-negative MPN (p<0.05). In PV patients, cardiovascular comorbidities were associated with a 4.5-fold increased risk of thrombosis (OR 4.59; CI 1.57-13.43; p=0.005). Mutated-JAK2 V617F MPN was associated with lower platelets and higher WBC count, while thrombosis was associated with higher hemoglobin and hematocrit (p<0.01). However, we found no associations between JAK2 V617F mutation and thrombotic events across all MPN subtypes. Conclusion Cardiovascular comorbidity are an independent risk factor for thrombosis in PV. While JAK2 V617F mutation was associated with distinct hematologic profiles, it was not independently linked to thrombotic risk. These findings highlight the significance of clinical comorbidities and hematologic parameters in thrombotic event occurrences in MPN patients.
Mutations in the RAS gene family (NRAS, KRAS) are critical drivers of late-stage acute myeloid leukemia (AML) progression. They are frequently detected in relapsed/refractory AML and AML transformed from myelodysplastic syndrome (MDS). Occurring as late-stage genetic events, RAS mutations synergize with early drivers to promote leukemogenesis. While mutually exclusive with FLT3-ITD mutations, they coexist with KIT, RUNX1, CEBPA mutations and MLL rearrangements. Granulocyte-monocyte progenitors (GMPs) serve as the cellular origin for RAS-mutant leukemia stem cells (LSCs). Ultimately, RAS mutations drive monocytic differentiation of LSCs and venetoclax (VEN) resistance through BCL-2 family rewiring. Beyond AML, they are hallmark genetic lesions in juvenile myelomonocytic leukemia (JMML) and present in 15%-20% of pediatric acute lymphoblastic leukemia (ALL) cases. Here, we propose a comprehensive pathogenic model and targeted therapeutic framework focusing on RAS, MCL-1, BCL2L1 to overcome drug resistance and improve patient outcomes.
Differentiation blockade is a central pathogenic hallmark of acute myeloid leukemia (AML). While all-trans retinoic acid (ATRA) achieves curative differentiation in acute promyelocytic leukemia (APL), this success has not extended to other AML subtypes. Recently, inhibitors targeting nucleotide metabolism-such as cytarabine, dihydroorotate dehydrogenase (DHODH) inhibitors, and DNA hypomethylating agents-have emerged as promising candidates to overcome this therapeutic barrier. These compounds promote myeloid maturation through mechanisms involving cell-cycle arrest, epigenetic reprogramming, and replication stress-activated signaling. Preclinical and early clinical evidence suggests that targeting nucleotide metabolism may induce partial differentiation of leukemic blasts, providing a metabolic and epigenetic avenue for therapy beyond APL. This mini-review summarizes current understanding of how metabolic inhibition restores differentiation in AML, focusing on representative agents and their mechanistic and translational implications. Targeting de novo nucleotide biosynthesis may offer a metabolic and epigenetic route to expand differentiation-based strategies beyond APL.
Glanzmann thrombasthenia (GT) is a rare autosomal recessive bleeding disorder from defects in the αIIbβ3 integrin receptor, impairing platelet aggregation and often overlooked due to normal platelet counts. Juvenile polyposis syndrome (JPS) is an autosomal dominant disorder with multiple gastrointestinal polyps and increased colorectal cancer risk. Their co-occurrence is exceedingly rare and challenging. We report a 19-year-old male who was diagnosed with GT at age 5 after rectal bleeding from a gastrointestinal polyp requiring polypectomy and transfusions; platelet aggregation studies confirmed GT. At age 9, genetic testing established JPS. In 2014 he developed recurrent severe bleeding—hematochezia, melena, and hemarthrosis—managed with recombinant activated factor VII (rFVIIa), blood transfusions, and supportive care including vitamin D. Additional findings included duodenal lymphangioma requiring resection, vitamin D deficiency with bone pain and complex regional pain syndrome, and chronic idiopathic hypertension treated with antihypertensives. This case highlights rFVIIa effectiveness and the need for multidisciplinary, long-term follow-up and care.
