Journal of hematology最新文献

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.

Background: Bolivian Andean Aymara highlanders, living at 4,000 m for 14,000 years, have evolved genetic adaptations to hypoxia. These include EGLN1 encoding prolyl hydroxylase 2 (PHD2), a regulator of transferrin transcription. Transferrin level increases in hypoxia and iron deficiency. Contrasting reports indicate that elevated transferrin is associated with experimentally induced thrombosis in mice undergoing short-stay at high altitude, but with decreased thrombosis in a congenital disorder of hypoxia-sensing.

Methods: A retrospective study was conducted in people living at high altitude (3,650 - 4,150 m). We analyzed serum transferrin concentration and thrombosis history in Aymara patients with high-altitude erythrocytosis (n = 149, median age 55 years, female gender 30%, iron deficiency 23%) or high-altitude anemia (n = 137, median age 43 years, female gender 86%, iron deficiency 57%).

Results: The median transferrin concentration was 339 mg/dL in erythrocytosis patients versus 310 mg/dL in anemia patients (P = 0.037); it was 367 mg/dL in iron deficient versus 312 mg/dL in iron replete patients (P < 0.001). Thrombosis history was present in 13% of erythrocytosis and 8% of anemia patients (P = 0.25) and was present in 16% of iron deficient and 7% of iron replete patients (P = 0.017). After adjustment for erythrocytosis and iron deficiency in multivariate regression analysis, the mean (95% confidence interval) transferrin concentration was 277 (237 - 316) mg/dL in 30 patients with thrombosis history versus 324 (306 - 341) mg/dL in 256 patients without thrombosis history (P = 0.018). Similar trends occurred for the subgroups of arterial thrombosis history (P = 0.044) and venous thrombosis history (P = 0.22).

Conclusions: In individuals with extreme environmental hypoxia, we found no evidence that increased transferrin is associated with increased thrombosis history. Rather, we observed a trend to decreased thrombosis history with increased transferrin levels.

Background: CD20-targeted therapies are widely used in the management of B-cell lymphomas. Re-treatment with CD20-directed agents is common; however, previous research has demonstrated loss of CD20 expression at relapse in a subset of patients.

Methods: In this single-center retrospective cohort of 243 patients, CD20 analysis was performed by immunohistochemistry (IHC) and/or flow cytometry at diagnosis and at relapse if a biopsy was performed.

Results: Of 109 patients with relapsed or refractory B-cell lymphoma, 59 patients with CD20-positive lymphoma at diagnosis underwent a biopsy at relapse for a total of 76 biopsies across all relapses. The rate of partial or complete CD20 expression loss was 11.9% (four patients with partial loss, three patients with complete loss). There were four cases of CD20 loss at first relapse (three IHC, one flow cytometry), two at second relapse (one IHC, one IHC and flow cytometry), and one at fifth relapse (IHC and flow cytometry). CD20 antigen escape was observed in marginal zone lymphoma, follicular lymphoma, and diffuse large B-cell lymphoma (DLBCL). All patients with CD20 expression loss previously received rituximab. Among patients with CD20 antigen escape, 85.7% had stage IV disease, and median overall survival after CD20 loss was 4 months. In the group of five patients with indolent lymphoma and CD20 expression loss, three patients (60%) had concurrent transformation to high-grade lymphoma.

Conclusions: This study, which reinforces the importance of repeating a biopsy at relapse before implementing CD20-directed therapy, is particularly relevant given the widespread use of rituximab along with the emerging significance of CD20-targeted bispecific antibodies in the management of B-cell lymphomas.

Immune checkpoint inhibitors (CPIs) can cause immune-related organ dysfunctions, including nephritis, pneumonitis, thyroiditis, hepatitis, colitis and more rarely hematological toxicities like immune-related autoimmune hemolytic anemia (irAIHA). Very few cases of irAIHA associated with immunotherapy have been reported, and treatment protocols remain unclear. This is partly because not all irAIHA cases are Coomb's test positive. Causes of anemia in cancer patients undergoing treatment with chemotherapy with or without immunotherapeutic agents can also be multiple. This makes it difficult to initially diagnose irAIHA, especially when CPIs are used concurrently with chemotherapy. Once alternate causes have been ruled out, a treatment plan for irAIHA is initiated based on grade of the anemia. Grade 1-2 irAIHA cases are managed with supportive interventions. However, cessation of therapy is recommended for life-threatening (grade 4) toxicity, severe (grade 3) toxicity that is recurring, or moderate (grade 2) toxicity that does not resolve with appropriate treatment for 3 months. Management of irAIHA usually involves methylprednisolone for 2 - 4 weeks with a slow taper after hemoglobin has normalized. But some cases do not respond to steroids alone and require cessation of immunotherapy or selecting alternate immunosuppressive agents. We report a protocol for treatment of grade 4 irAIHA secondary to programmed death protein 1 (PD-1) blocker pembrolizumab.

Background: Anemia is a global health issue that affects over 1 billion people and contributes to maternal mortality and birth defects. Low-resource, tropical areas face a dual challenge: high prevalence of anemia and inability to access affordable testing methods. The falling drop hemoglobin method has been developed by our lab to quantify hemoglobin concentration and assess anemia by timing the descent of venous blood in a column of copper sulfate solution, without using electricity or batteries. This research aimed to optimize the falling drop hemoglobin method by evaluating the use of capillary blood to reduce within sample variance and assessing copper sulfate stability to determine shelf life in expected working conditions.

Methods: The falling drop hemoglobin method was performed on both venous and capillary blood samples collected directly from the fingertip by dispensing 44 µL of blood in a copper sulfate column. A microhematocrit was performed on the venous blood sample and converted mathematically to a hemoglobin level to serve as the standard. Copper sulfate stability was assessed for 32 weeks among three solutions: solution prepared fresh on day of testing, solution incubated at room temperature, and solution incubated at 37.7 °C.

Results: Capillary blood yielded higher average descent times and higher standard deviations than venous blood. Collecting precisely 44 µL of capillary blood proved challenging and impractical. In copper sulfate stability testing, freshly prepared solution yielded the highest average descent time. A one-way analysis of variance (ANOVA) test and Tukey's honestly significant difference (HSD) post hoc testing revealed no significant difference between mean descent times of freshly prepared and 37.7 °C solutions (P = 0.26) and between room temperature and 37.7 °C solutions (P = 0.64), but a significant difference between freshly prepared and room temperature solutions (P = 0.04).

Conclusions: This study found that capillary blood did not present a more accurate alternative to venous blood in the falling drop hemoglobin test, and copper sulfate did not degrade over 32 weeks at 37.7 °C. This lends support for the current use of venous blood in the test, and for use of copper sulfate solution in tropical climates, where the test is most necessary, with a shelf life of at least 32 weeks.

Plasmablastic lymphoma (PBL) is a malignant lymphoma with poor prognosis that occurs in immunocompromised and elderly patients. We describe the case of a 75-year-old woman with PBL as a methotrexate-associated lymphoproliferative disorder (MTX-LPD). She presented with multiple oral ulcers and mass-like shadows in the lung fields. Biopsy of the oral ulcer revealed medium to large irregular round monotypic B cells positive for cluster of differentiation (CD)138, CD79a, immunoglobulin λ, and Epstein-Barr virus-encoded small ribonucleic acid in situ hybridization, and PBL was diagnosed. The patient showed negative results for human immunodeficiency virus and had a history of taking MTX for rheumatoid arthritis, suggesting MTX-LPD. Following discontinuation of MTX, the oral ulcers resolved 1 month later without recurrence, and lung lesions decreased in size over time. Because MTX-LPD can take the form of PBL and may resolve with MTX withdrawal alone, therapeutic interventions should be carefully considered. While PBL is typically highly aggressive and requires prompt treatment, MTX-LPD cases can sometimes resolve without further treatment, depending on the clinical course. However, in cases where the disease shows progression or when spontaneous regression does not occur, additional therapeutic interventions may be necessary to manage the disease effectively.