Journal of hematology最新文献

Primary central nervous system lymphoma (PCNSL) is an aggressive form of extranodal non-Hodgkin lymphoma that arises in the brain parenchyma, eyes, meninges, or spinal cord in the absence of systemic disease. Primary dural lymphoma (PDL), in contrast, arises from the dura mater of the brain. PDL is usually a low-grade B-cell marginal zone lymphoma (MZL), whereas other types of PCNSL are usually high-grade large B-cell lymphoma. This specific pathological subtype has important therapeutic and prognostic implications, making PDL a distinct subtype of PCNSL. Herein, we report a case of PDL in an African American patient, in her late thirties, who presented to our emergency room with chronic headaches. An emergent magnetic resonance imaging (MRI) of the brain showed a dural-based homogeneously enhancing extra-axial mass along the left hemisphere, which was contained within the anterior and parietal dural mater. A surgical specimen was collected after an emergency debulking procedure. The flow cytometry, done on the surgical specimen obtained, was positive for CD19⁺, CD20⁺, and CD22⁺, but negative for CD5^- and CD10^-. These findings were consistent with a clonal B-lymphoproliferative disorder. The surgical pathology specimen immunohistochemistry was positive for CD20⁺ and CD45⁺, but negative for Bcl-6Cyclin D1^- and CD56^-. The Ki67 was 10-20%. These findings were consistent with extranodal MZL. Given the location and pathology, the patient was diagnosed with PDL. Due to MZL's indolent nature, location outside the blood-brain barrier, and known efficacy to bendamustine-rituximab (BR), we decided to treat our patient with BR. She completed six cycles without major complications, and her post-therapy brain MRI showed complete remission (CR). Our case adds to the sparse literature about PDL and highlights the efficacy of BR systemic chemotherapy on MZLs.

Background: Immune checkpoint inhibitors (ICIs) have been a breakthrough in cancer therapy. ICI therapy is generally better tolerated than cytotoxic chemotherapy; however, hematological adverse events (AEs) have not been fully analyzed. Hence, we performed a meta-analysis to evaluate the incidence and risk of ICI-related hematological AEs.

Methods: A systematic literature search was performed using PubMed, EMBASE, Cochrane Library, and the Web of Science Core Collection. Phase III randomized controlled trials (RCTs) involving ICI combination regimens were selected. The experimental group received ICIs with systemic treatment, and the control group received only the same systemic treatment. Odds ratios (ORs) for anemia, neutropenia, and thrombocytopenia were calculated using a random-model meta-analysis.

Results: We identified 29 RCTs with 20,033 patients. The estimated incidence rates for anemia of all grades and grades III-V were 36.5% (95% confidence interval (CI) 30.23 - 42.75) and 4.1% (95% CI 3.85 - 4.42), respectively. The incidence of neutropenia (all grades 29.7%, grades III-V 5.3%) and thrombocytopenia (all grades 18.0%, grades III-V 1.6%) was also calculated.

Conclusion: Treatment with ICIs seemed unlikely to increase the incidence of anemia, neutropenia, and thrombocytopenia in all grades. However, programmed cell death-1 receptor ligand inhibitors significantly increased the risk of grades III-V thrombocytopenia (OR 1.53; 95% CI 1.11 - 2.11). Further research is needed to examine the potential risk factors.

Neutropenic enterocolitis (NEC) is a life-threatening condition occurring in severely neutropenic patients, following intensive chemotherapy for leukemia. Its pathogenesis is not entirely understood and believed to be multifactorial, including mucosal injury as a result of cytotoxic drugs, profound neutropenia, impaired host defense and possibly microbiota changes. Establishing an early diagnosis is key. The management of NEC remains undefined due to lack of high-quality clinical data. With a better understanding of the disease, a more conservative approach is preferred over surgical intervention. The involvement of a multi-disciplinary team, consisting of the oncologist, infectious diseases specialists and surgeons is highly recommended. This review aims to delineate insights into the pathophysiology and clinical presentation of NEC and to emphasize the diagnostic and therapeutic approach to this condition.

The clinicopathology entity of plasmablastic lymphoma (PBL), despite broad recognition by the World Health Organization (WHO), represents a diagnostic challenge due to its overlapping features and scarce occurrence. Often, PBL arises in immunodeficient, elderly male patients, most notably those who are human immunodeficiency virus (HIV)-positive. More infrequent, cases of transformed PBL (tPBL) evolved from another hematologic disease have been identified. Herein, we describe a case of a 65-year-old male transferred from a neighboring hospital with pronounced lymphocytosis and spontaneous tumor lysis syndrome (sTLS) presumed to be chronic lymphocytic leukemia (CLL). Utilizing a complete clinical, morphologic, immunophenotypic, and molecular evaluation, we arrived at a final diagnosis of tPBL with sTLS, suspected to have evolved from the NF-κB/NOTCH/KLF2 (NNK) genetic cluster of splenic marginal zone lymphoma (SMZL) (NNK-SMZL), a potential transformation and presentation, to our knowledge, not previously reported. However, definitive clonality testing was not performed. In this report, we also outline the diagnostic and educational considerations we faced in discerning tPBL from other more common B-cell malignancies which can present similarly, such as CLL, mantle cell lymphoma, or plasmablastic myeloma. We summarize recently reported molecular, prognostic, and therapeutic considerations for the treatment and recognition of PBL, including the successful implementation, in our patient, of bortezomib to an EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) regimen with prophylactic intrathecal methotrexate, who has since achieved complete remission (CR) and entered clinical surveillance. Lastly, this report briefly highlights the challenge we faced in this area of hematologic typification that necessitates additional review and discussion by the WHO: tPBL with potential double-hit cytogenetic versus double-hit lymphoma with a plasmablastic phenotype.

Background: Daratumumab, pomalidomide, and dexamethasone (DPd) is an effective option for treatment of patients with relapsed/refractory multiple myeloma (RRMM). In this study, we sought to analyze the risk of hematological and non-hematological toxicities in patients who responded to DPd treatment.

Methods: We analyzed 97 patients with RRMM who were treated with DPd between January 2015 and June 2022. The patients and disease characteristics, as well as safety and efficacy outcomes were summarized as descriptive analysis.

Results: The overall response rate for the entire group was 74% (n = 72). The most common grade III/IV hematological toxicities in those who responded to treatment were neutropenia (79%), leukopenia (65%), lymphopenia (56%), anemia (18%), and thrombocytopenia (8%). The most common grade III/IV non-hematological toxicities were pneumonia (17%) and peripheral neuropathy (8%). The incidence of dose reduction/interruption was 76% (55/72), which was due to hematological toxicity in 73% of the cases. The most common reason for discontinuing treatment was disease progression in 61% (44 out of 72 patients).

Conclusions: Our study revealed that patients who respond to DPd are at high risk of dose reduction or treatment interruption because of hematological toxicity, typically due to neutropenia and leukopenia leading to increased risk of hospitalization and pneumonia.

T-lymphoblastic leukemia/lymphoma (T-ALL/T-LBL) is a malignancy comprised of T-lymphoblasts that can present as one of four clinical subtypes (pro-T, pre-T, cortical T, and mature T). Clinical presentation is typically characterized by leukocytosis with diffuse lymphadenopathy and/or hepatosplenomegaly. Beyond clinical presentation, specific immunophenotypic and cytogenetic classifications are utilized to diagnose mature T-ALL. In later disease stages it can spread to the central nervous system (CNS); however, presentation of mature T-ALL by way of CNS pathology and clinical symptomatology alone is rare. Even more rare is the presence of poor prognostic factors without correlating significant clinical presentation. We present a case of mature T-ALL in an elderly female with isolated CNS symptoms in combination with poor prognostic factors including terminal deoxynucleotidyl transferase (TdT) negativity and a complex karyotype. Our patient lacked the classical symptomatology and laboratory findings of mature T-ALL but deteriorated quickly upon diagnosis due to the aggressive genetic profile of her cancer.

Background: Data on whether the graft CD3-positive (CD3⁺) T-cell dose in T-cell-replete human leukocyte antigen (HLA)-mismatched allogeneic hematopoietic peripheral blood stem cells transplantation (PBSCT) influences post-transplant outcomes are controversial.

Methods: Using King Hussein Cancer Center (KHCC) Blood and Marrow Transplantation (BMT) Registry database, 52 adult subjects, receiving the first T-cell-replete HLA-mismatched allogeneic hematopoietic PBSCT for acute leukemias or myelodysplastic syndrome, were identified, from January 2017 to December 2020. The cutoff value of graft CD3⁺ T-cell dose was identified using the receiver operating characteristic (ROC) formula and Youden's analysis. Subjects were divided into two cohorts: cohort 1 with low CD3⁺ T-cell dose (n = 34) and cohort 2 with high CD3⁺ T-cell dose (n = 18). Correlative analyses were performed between CD3⁺ T-cell dose and the risk of graft-versus-host disease (GvHD), relapse, relapse-free survival (RFS), and overall survival (OS). P-values were two-sided and considered significant when P < 0.05.

Results: Subject covariates were displayed. Subject's characteristics were comparable, except for higher nucleated cells and more female donors in the high CD3⁺ T-cell cohort. The 100-day cumulative incidence of acute GvHD (aGvHD) was 45±7% and 3-year cumulative incidence of chronic GvHD (cGvHD) was 28±6.7%. There was no statistically significant difference between the two cohorts in aGvHD (50% vs. 39%, P = 0.4) or cGvHD (29% vs. 22%, P = 0.7). The 2-year cumulative incidence of relapse (CIR) was 67.5±16.3% for low compared with 14.3±6.8% for high CD3⁺ T-cell cohort (P = 0.018). Fifteen subjects relapsed and 24 have died, 13 due to disease relapse. There was an improvement in 2-year RFS (94% vs. 83%; P = 0.0022) and 2-year OS (91% vs. 89%; P = 0.025) in low CD3⁺ T-cell cohort compared with high CD3⁺ T-cell cohort. Graft CD3⁺ T-cell dose is the only significant risk factor for relapse (P = 002), and OS (P = 0.030) in univariate analysis which was maintained in multivariate for relapse (P = 0.003), but not for OS (P = 0.050).

Conclusions: Our data suggest that high graft CD3⁺ T-cell dose is associated with lower risk of relapse, and might improve long-term survival, but has no influence on the risk of developing aGvHD or cGvHD.

Background: Despite pronounced improvement in overall survival (OS) in pediatric leukemia, a proportion of patients continue to suffer from lack of response or relapse, and the management of such patients is exceedingly difficult. Immunotherapy and engineered chimeric antigen receptor (CAR) T-cell therapy have shown promising results in the course of relapsed or refractory acute lymphoblastic leukemia (ALL). However, conventional chemotherapy continues to be utilized for re-induction purposes whether independently or in combination with immunotherapy.

Methods: Forty-three pediatric leukemia patients (age < 14 years at diagnosis) consecutively diagnosed at our institution and got treated with clofarabine based regimen at a single tertiary care hospital between January 2005 and December 2019 were enrolled in this study. ALL comprised of 30 (69.8%) patients of the cohort while the remaining 13 (30.2%) were with acute myeloid leukemia (AML).

Results: Post-clofarabine bone marrow (BM) was negative in 18 (45.0%) cases. Overall clofarabine failure rate was 58.1% (n = 25) with 60.0% (n = 18) in ALL and 53.8% (n = 7) in AML (P = 0.747). Eighteen (41.9%) patients eventually underwent hematopoietic stem cell transplantation (HSCT); 11 (61.1%) were from ALL group and remaining seven (38.9%) were AML (P = 0.332). Three- and 5-year OS of our patients was 37.7±7.6% and 32.7±7.3%. There was a trend of better OS for ALL patients compared to AML (40.9±9.3% vs. 15.4±10.0%, P = 0.492). Cumulative probability of 5-year OS was significantly better in transplanted patients (48.1±12.1% vs. 21.4±8.4%, P = 0.024).

Conclusions: Though almost 90% of our patients proceeded to HSCT with complete response post-clofarabine treatment, yet clofarabine-based regimens are associated with the significant burden of infectious complications and sepsis-related deaths.

Anaplastic large cell lymphoma (ALCL) is children's most common mature T-cell neoplasm. The majority is positive for anaplastic lymphoma kinase (ALK). Initial presentation as a soft-tissue pelvic mass without nodal involvement is rare and can be easily misdiagnosed. We report a case of a 12-year-old male presenting with pain and movement restriction in the right extremity. Computed tomography (CT) scan revealed a solitary pelvic mass. Initial biopsy examination concluded rhabdomyosarcoma. After developing pediatric multisystemic inflammatory syndrome due to coronavirus disease 2019 (COVID-19), central and peripheral lymph node enlargement appeared. New cervical adenopathy and pelvic mass biopsies were performed. Immunohistochemistry concluded an ALK-positive ALCL with a small-cell pattern. The patient was treated with brentuximab-based chemotherapy and eventually improved. Differential diagnosis of pelvic masses in children and adolescents must include ALCL. An inflammatory trigger may promote the appearance of a typical nodal disease, previously absent. Attention is warranted during histopathological examination to avoid diagnostic errors.

Background: Acute myeloid leukemia (AML) is a hematological neoplasm that is more frequent in elderly patients. The objective of this study was to evaluate elderly patients' survival with de novo AML and acute myeloid leukemia myelodysplasia-related (AML-MR), treated with intensive and less-intensive chemotherapy and supportive care.

Methods: A retrospective cohort study was conducted in Fundacion Valle del Lili (Cali, Colombia), between 2013 and 2019. We included patients ≥ 60 years old diagnosed with AML. The statistical analysis considered the leukemia type (de novo vs. myelodysplasia-related) and treatment (intensive chemotherapy regimen, less-intensive chemotherapy regimen, and without chemotherapy). Survival analysis was performed using Kaplan-Meier method and Cox regression models.

Results: A total of 53 patients were included (31 de novo and 22 AML-MR). Intensive chemotherapy regimens were more frequent in patients with de novo leukemia (54.8%), and 77.3% of patients with AML-MR received less-intensive regimens. Survival was higher in the chemotherapy group (P = 0.006), but with no difference between chemotherapy modalities. Additionally, patients without chemotherapy were 10 times more likely to die than those who received any regimen, independent of age, sex, Eastern Cooperative Oncology performance status, and Charlson comorbidity index (adjusted hazard ratio (HR) = 11.6, 95% confidence interval (CI) 3.47 - 38.8).

Conclusions: Elderly patients with AML had longer survival time when receiving chemotherapy, regardless of the type of regimen.