Journal of hematology最新文献

Central nervous system lymphoma (CNSL) is an aggressive disease with limited well-studied options for treatment, especially refractory treatment. First-line treatment usually includes high-dose methotrexate (HD-MTX) for induction and either autologous stem cell transplantation or whole-brain radiation therapy (WBRT) as consolidation. However, WBRT can result in significant neurotoxicity, so the use of focal radiation (i.e., gamma knife-stereotactic radiosurgery (GK-SRS)) of varying doses and fractions has been proposed. In the case of refractory disease, chimeric antigen receptor (CAR) T-cell therapy has begun to be used clinically, but patients with CNS involvement were left out of key approval trials. Here, we present a case of a 62-year-old patient with refractory secondary CNSL (SCNSL) previously treated with WBRT who was successfully treated with a combination of CAR T-cell therapy and GK-SRS.

Post-transplant lymphoproliferative disorder (PTLD) is a potentially life-threatening complication, often associated with Epstein-Barr virus (EBV) in the early period after hematopoietic stem cell transplantation (HSCT). Clinical manifestations range from localized to disseminated disease. The cornerstone of therapy is the reduction of immunosuppression and/or immunochemotherapy. We report a 39-year-old female who developed PTLD presenting as lymphoplasmacytic lymphoma (LPL) associated with hemophagocytic lymphohistiocytosis (HLH). Diagnostic evaluation was blurred by features of severe hepatic acute graft-versus-host disease (GVHD). An initial treatment consisted of high-dose steroids, but it failed. As second-line treatment, ruxolitinib and mycophenolate mofetil were administered, but they were ineffective, and the patient's condition worsened. Further detailed evaluation revealed the presence of monoclonal protein immunoglobulin G (IgG) lambda and bone marrow infiltration by clonal plasmacytoid B lymphocytes. The HLH criteria were also met. Immunosuppression was discontinued, and dexamethasone with rituximab was initiated, but no response was observed. The patient eventually died from multiple organ failure. The learning points from this case emphasize that HLH in the context of PTLD remains underreported, with few cases documented in the literature. Studies indicate that EBV plays a central role in pathogenesis, often presenting with systemic inflammation and immune dysregulation. Diagnostic challenges arise due to overlapping clinical features with other post-transplant complications. Treatment strategies vary but often involve balancing immunosuppression reduction and chemotherapy, with rituximab being a cornerstone for EBV-driven cases. This case underscores the necessity of early recognition to mitigate severe outcomes.

Background: Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy with an incidence of 30% of pediatric cancers across the world and 34% amongst Saudi children with cancers. Minimal residual disease (MRD) is considered the most important independent predictor in determining the risk of relapse and long-term outcomes in ALL patients and plays a pivotal role in guiding risk-adapted therapies. The aim of this research was to study the role of MRD on survival benefits in our patient population.

Methods: We reviewed medical records of 108 pediatric (age ≤ 14 years) ALL patients treated between January 2016 and December 2018 at our center to assess if MRD and other associated risk factors affect the outcome of patients at post-induction and post-consolidation phases of the treatment protocols.

Results: The median follow-up time in our cohort of patients was 75.6 months (95% confidence interval: 71.3 - 79.8 months). With a mortality rate of 10.2% (11 deaths out of 108 cases), overall survival (OS) of the whole cohort was 89.2±3.1%. OS was significantly lower in post-induction MRD-positive cases than in MRD-negative cases (74.2±8.6% vs. 94.7±2.6%, P = 0.006). It was worse among those patients who underwent consolidation therapy and had positive post-consolidation MRD. Event-free survival (EFS) was also significantly poor in post-induction MRD-positive cases (61.1±10.2% vs. 92.1±3.1%, P = 0.001). Twenty-seven patients who received consolidation therapy had the poorest EFS (P = 0.031). Amongst all the factors, including age at diagnosis, gender, white blood cell count, central nervous system status, risk group or cytogenetics, only post-induction MRD positivity was found to be significantly associated with OS.

Conclusion: Post-induction MRD is one of the most important factors affecting the patient's outcome. Post-induction MRD-positive patients fared better after receiving consolidation therapy. No significant association was found between post-induction MRD and other risk factors.

De novo extramedullary multiple myeloma (EMM) is a rare subset of multiple myeloma (MM) defined by the presence of clonal plasma cells (PC) outside of the bone marrow. It is associated with refractory disease and adverse outcomes. Even in EMM, plasmacytomas within the duodenum, jejunum, and ileum are uncommon, with fewer than 70 cases reported in the literature. Here, we present a particularly aggressive case of EMM resulting in a small bowel obstruction secondary to an intraluminal plasmacytoma while on myeloma-directed therapy. The patient underwent surgical resection with anastomosis and was transitioned to more definitive cytotoxic chemotherapy followed by autologous stem cell rescue. This case highlights challenges in the management of EMM over standard MM and argues that dedicated clinical trials for patients with aggressive EMM are warranted to further understand the unique pathophysiology and improve overall survival.

Induction multiagent chemotherapy can cure 70% of adult Burkitt lymphoma patients. However, for the remaining patients, the majority will relapse either during induction chemotherapy or within 6 months after initial complete remission, as in our patient. In this life-threatening presentation where no standard therapy exists with a response rate to salvage chemotherapy of 0% and a median survival of 6 weeks, there is an urgent need for novel, effective approaches to overcome chemoresistance in Burkitt lymphoma. Our report demonstrates that targeting B-cell receptor signaling via the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway with copanlisib can overcome chemotherapy resistance and achieve complete remission in relapsed Burkitt lymphoma. This novel approach, followed by consolidation with allogeneic hematopoietic stem cell transplantation can provide durable complete remission by harnessing the immune graft-versus-lymphoma effect in chemoresistant Burkitt lymphoma.

Mast cell leukemia (MCL) is a rare and aggressive form of systemic mastocytosis (SM) that commonly involves the bone. This often presents as osteoporosis with focal osteolytic lesions and pathological fractures. Osteoblastic (sclerotic) lesions are rarely seen in MCL. The vertebral bodies are the most common site of bone involvement, with lesions outside of the axial skeleton being extremely rare. MCL presenting with osteoblastic lesions has been reported in the literature, however, there are no reported cases of osteoblastic lesions in the appendicular skeleton. Here we report a rare case of acute aleukemic MCL that presented with diffuse osteoblastic/sclerotic osseous lesions involving ribs, thoracic spine, lumbar spine and pelvis without pathological fractures.

Background: The incidence of central nervous system (CNS) relapse in diffuse large B-cell lymphoma (DLBCL) varies, and the optimum strategy of CNS prophylaxis remains to be defined. We aimed to evaluate the incidence of CNS relapse in DLBCL patients and the role of CNS prophylaxis.

Methods: Data on patients diagnosed with DLBCL at our institution from January 2011 to June 2019 were retrospectively collected from the charts and computerized hospital information system for patient demographics, lymphoma stage at diagnosis, CNS international prognostic index (IPI) scores, extra-nodal sites, chemotherapy type, CNS prophylaxis, and CNS relapse. CNS prophylaxis comprised intrathecal (IT) chemotherapy and was administered based on the presence of high-risk features. Patients with primary CNS lymphoma and CNS involvement at diagnosis were excluded.

Results: Of 101 patients, 58 (57.5%) were males with a median age of 56 (range: 16 - 87) years. Ann Arbor stages of I - IV were confirmed in nine, 21, 17, and 50 patients, respectively. The lung was the most common extranodal site involved (27, 26.7%). Twenty-five (24.75%) patients had a high-risk CNS-IPI score. Ninety-three percent of patients received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. Sixteen patients received CNS prophylaxis as IT methotrexate (± cytarabine and hydrocortisone). Despite high-risk CNS-IPI scores, nine (36%) patients did not receive CNS prophylaxis. After a median follow-up of 36 (range: 4 - 114) months, two patients with high-risk CNS-IPI score developed CNS relapse and died shortly.

Conclusions: CNS relapse of DLBCL was uncommon in this patient population. Low incidence of CNS relapse despite limited use of IT prophylaxis may suggest adequacy of IT prophylaxis in these patients.

Background: Graft rejection (GR) occurs in a significant proportion of individuals with transfusion-dependent β-thalassemia (TDT) following hematopoietic stem cell transplantation (HSCT). There have been limited data on the outcome and complications of second HSCT in β-thalassemia patients. The objective was to assess the survival benefits and outcome of second allogeneic HSCT in pediatric TDT patients using Cytoxan (CY) and total body irradiation (TBI) regimen.

Methods: This was a retrospective study on the analysis of the data for 15 patients who had graft failure over an 18-year period (March 2000 to March 2017) at our institution. For the first failed transplants for patients who had a myeloablative regimen consisting of busulfan (BU)-CY with or without additional anti-thymocyte globulin (ATG), the median age at transplant was 4.2 years. Graft failure occurred over a median of 8.6 months (range, 0.6 - 74.3 months) after the first transplant. The median time to the second transplant from GR was 25.3 months. For the second transplant, the same human leukocyte antigen (HLA) match-related donors for the first HSCT were used. Over half of the patients had moderate to severe iron overload with pre-transplant serum ferritin of 1,405 to 4,051 µg/L at transplant.

Results: Thirteen patients (86.7%) engrafted with thalassemia-free survival (TFS) of 80.0%. One patient rejected the graft and died. Another died due to infectious complications. Apart from a mild chronic graft-versus-host disease (GvHD) in one patient, no serious complications were observed.

Conclusion: CY-TBI can be used as conditioning for second HSCT in patients with TDT GR following myeloablative conditioning. We observed overall survival and TFS of 87% and 80% respectively with low rejection rate and mortality, and limited long-term side effects.

Background: Pediatric hematopoietic stem cell transplant (pHSCT) patients are at risk for many life-threatening post-transplant complications, notably relapse, graft-versus-host disease (GvHD), and infection.

Methods: This retrospective study reviewed 10 years of pHSCT at a single institution, assessing for risk factors for post-transplantation viral infections (herpes simplex virus (HSV), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpes virus 6 (HHV6), adenovirus (ADNV), and human polyoma virus 1 (BK virus)), and characterizing adverse infectious outcomes.

Results: Overall, 139 patients received 151 transplants. With respect to graft source: 73 (48.3%) were bone marrow, 67 (44.4%) umbilical cord blood (UCB), and 11 (7.2%) peripheral blood stem cells (PBSCs). Forty-one deaths occurred, for an overall mortality rate of 29.5%. The overall incidence of post-transplant viral infections was 47.7% (n = 72). Incidence of post-transplant infection varied by virus type: 3.97% HSV, 0.67% VZV, 3.97% EBV, 24.5% CMV, 14.5% HHV6, 12.6% ADNV, and 12.6% BK virus. Viral encephalitis, though relatively uncommon, was primarily caused by HHV6 and more common in UCB transplants. Overall, cell source and donor source were identified with statistically significant correlation to both risk of infection and mortality.

Conclusions: Post-transplant viral infection remains as a serious adverse event in pediatric patients, and thus prospective studies should be performed to implement early intervention and more aggressive treatment in select high-risk patients. More studies specifically addressing infection risks in cord blood transplants and risk factors for post-transplant viral encephalitis are warranted.