Journal of hematology最新文献

Background: A combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is considered the standard treatment for diffuse large B-cell lymphoma (DLBCL). However, no standard treatment has been established for older patients (age ≥ 75 years). This study retrospectively analyzed different treatment strategies in older patients with DLBCL with different chemotherapy regimens and compared the survival rate of patients using oral or intravenous form cyclophosphamide and etoposide in a single center.

Methods: We reviewed the records of older patients with DLBCL, aged ≥ 75 years, from January 2010 to August 2019. The different treatment combinations, clinical characteristics, response rates, and toxicity profiles were analyzed. The median overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier (KM) method. Cox regression model was used to identify the risk factors.

Results: Eighty-four patients were included. One-quarter of the patients received cytoreduction treatment because of their poor medical condition at the time of diagnosis. Twenty-six percent of the patients were aged ≥ 85 at the time of diagnosis and 46.7% completed the treatment course. Patients receiving non-anthracycline-containing (non-ACR) treatment had worse Charlson comorbidity index, worse PFS, lower body mass index, or were older. The mean anthracycline accumulative dose in the anthracycline-containing (ACR) group was 134 mg/m². The median OS was 17.2 months and median PFS was 7.7 months. The PFS of R-CHOP is better than R-mini-CHOP and R-CVOP without statistical significance, but OS of R-CHOP is not better than the other regimens.

Conclusion: The toxicity, efficacy, and KM curve for OS and PFS in the non-ACR group were lower compared to ACR group, without statistical significance. R-CVOP had similar OS with R-mini-CHOP in our study. The result does not mean etoposide could totally substitute for anthracycline, but etoposide did have lower early progression rate (12.5%), and it may be an option for frail patients with comorbidity. Oral form cyclophosphamide and etoposide could be considered as a substitute for intravenous administration because of the similar effect and toxic profile.

Coronavirus disease 2019 (COVID-19) has spread tremendously since its first appearance in December 2019. Infected individuals can experience a wide range of systemic complications, including thrombotic microangiopathy (TMA). Like the other forms of TMA, COVID-19-associated TMA is characterized by thrombocytopenia, hemolytic anemia, and organ failure (such as acute kidney injury). The role of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in COVID-19-associated TMA is most probably dual: it can act either as a trigger to an underlying condition or as a cause of TMA. As opposed to the majority of other reported cases, it may be that in our case COVID-19 was the only cause of TMA. We present a case of a 32-year-old previously healthy man who was treated for acute kidney injury associated with TMA, which we believe was caused by COVID-19. Thrombotic thrombocytopenic purpura, as well as other possible known causes of typical and atypical hemolytic-uremic syndrome, was excluded. During his hospitalization, three negative nasopharyngeal swabs for SARS-CoV-2 were obtained, but serological tests showed the presence of IgG and IgA antibodies. After initial treatment known to be helpful in other forms of TMA (therapeutic plasma exchange and methylprednisolone), his renal function and platelet count recovered completely. Our case illustrates the importance of quickly recognizing this life-threatening complication of COVID-19 and using treatment that has been shown to be beneficial in other forms of TMA. Future studies of the pathophysiology and subsequent targeted treatment of this novel disease are needed.

Programmed cell death protein 1 (PD-1) checkpoint inhibitors such as pembrolizumab are novel therapeutics used to treat various advanced malignancies and have been shown to increase patient survival in several studies. However, these drugs have a toxicity profile that ranges from mild side effects such as dermatitis to life-threatening complications. We present a case of pembrolizumab-induced hemophagocytic lymphohistiocytosis (HLH) in an 80-year-old patient with squamous cell carcinoma (SCC) of presumed cutaneous primary. This patient initially presented with weakness and pancytopenia, thought to be immune-related. She developed progressive anemia, after which further workup revealed concern for HLH. She recovered after a course of steroids, tocilizumab, and etoposide. To our knowledge, this patient's course is among a few rare cases of immune checkpoint inhibitor (ICI)-mediated HLH. This case highlights the need for early diagnosis and recognition of HLH as a potential toxicity related to ICI therapy.

Light chain deposition disease (LCDD) is a rare hematologic disorder that can affect any organ but predominantly involves the kidneys. Existing literature is limited to case reports and small single-center retrospective series, explaining the lack of any treatment algorithms and management guidelines for patients with this disorder. In this systematic review of literature, we explored the role of standard and high-dose chemotherapy-autologous stem cell transplant for LCDD. A total of 11 studies were identified to evaluate the hematologic and renal responses to various treatment regimens. Autologous stem cell transplant and bortezomib-based regimens appear to have reasonable safety and efficacy for this rare hematologic disorder, albeit some statistical and analytical limitations. Large multicenter retrospective and prospective studies are needed to better elucidate the role of various chemotherapy regimens as well as autologous stem cell transplant for patients with LCDD.

Background: Langerhans cell histiocytosis (LCH) is a rare inflammatory myeloid neoplasia belonging to the group of histiocytoses. Inflammatory tissue destruction with fibrosis can result in dysfunction in any organ. Our evaluation aimed to collect information on characteristics, courses, and therapeutic options of this rare disease pattern in adult patients with conclusions on prognostic factors and follow-up management.

Methods: The medical records of 194 adult patients with histologically confirmed LCH were evaluated in this retrospective study. Patients were treated at the Protestant Clinics in Gelsenkirchen from 2000 to 2014 and St. Franziskus-Hospital in Cologne until 2020.

Results: The median age of onset was 38 years (18 to 79 years). In 65.5% of patients, only one organ was primarily involved, and in 34.5% of cases, multiple organs were involved. The skeleton, lungs, and skin were most commonly affected. In 15.5% of patients, pituitary insufficiency existed years before or at the time of diagnosis. The follow-up time of patients from the time of histologic diagnosis ranged from 6 to 408 months (median 49 months). Four patients died from sequelae of their underlying histiocytic disease. Irreversible late sequelae due to disease or therapy were detectable in 34% of patients. In 25.3% of the patients, the course of the disease could be controlled initially, but with the proviso of no smoking in case of lung involvement. Specific therapeutic measures such as surgery for solitary osteolysis, radiotherapy of osseous and cerebral manifestations, immunotherapy especially for lung and skin involvement, and chemotherapy for multisystem disease were primarily required in 74.7% of patients. As a result, 27.3% of all patients reached the nonactive stage. Of these, 26.4% had reactivation during the follow-up period. Of the remaining patients with continued active disease, 51.1% showed disease progression during follow-up.

Conclusions: Standardized diagnostics are required to capture the clinical picture. Due to the variable course, it is often sufficient to initially control with obligatory smoking cessation in case of pulmonary involvement. Follow-up examinations should be predominantly symptom-oriented with attention to possible late sequelae.

A 49-year-old woman with systemic lupus erythematosus, lupus nephritis and chronic congestive heart failure presenting with "bulky" cervical lymphadenopathy was diagnosed with classic Hodgkin lymphoma (HL) stage IIIB (positron emission tomography-computed tomography (PET-CT) scan and bone marrow biopsy). She received one cycle of bleomycin, dacarbazine, and vinblastine to debulk the tumor. Given her advanced heart failure, doxorubicin was not administered. After the first cycle of chemotherapy, she was switched to nivolumab plus brentuximab vedotin (BV) and received two doses 4 weeks apart, finishing in July 2019. A restaging PET-CT in June 2019 showed a complete remission (CR). After the second course of treatment, she was unable to tolerate more treatments and hence was placed on a surveillance program. She remains in CR after a follow-up of 3 years. This case highlights the role of a tailored treatment approach to optimize clinical outcomes in uniquely complex clinical circumstances. BV in combination with nivolumab is a reasonable alternative regimen in HL ineligible for cytotoxic chemotherapy.

Background: The sickle cell trait (SCT) disorder possesses a clinical heterogeneity ranging from a symptomless condition to sudden death. This study aimed to develop a diagnostic approach that helps the characterization and identification of SCT from normal subjects and sickle cell disease (SCD) patients, and to assess its severity.

Methods: Sixty controls, 24 SCD patients and 31 SCT subjects were assessed clinically, radiologically and by laboratory investigations.

Results: Of the SCT subjects, 12.8% were symptomatic (3.2% anemic, 6.4% hemolytic crisis, and 3.2% painful crises). Anemia was normocytic in 66.6%, and normochromic and polychromatic in 33.4%. Significantly lower red blood cells (RBCs), hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), hematocrit (Hct), Shine and Lal index (SL), and hemoglobin A (Hb A), and higher mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), Ricerca index (RI), and Huber-Herklotz index (HH) were found in SCT subjects compared with the controls. Hb A and hemoglobin S (Hb S) were excellent in discriminating SCT from SCD (cut-off for SCT > 50% and < 40%) followed by Hct, MCHC, Hb, Green and King index (GK), and England and Fraser index (EF) (cut-off for SCT > 33%, > 32, > 11, < 71, and < 10, respectively). Radiologically normal findings were detected in 87% of SCT subjects; they had nearly normal liver and renal function tests (except one case each). A schematic diagnostic paradigm for SCT was proposed.

Conclusion: This study allowed understanding of SCT in various aspects, i.e., clinical, hematological, biochemical and radiological. Thus, it could help prevention of the Hb S variant disorder and proper management of carriers. This might be applied in pre-marital screening, particularly in those with family history of Hb S disorder.

Immune checkpoint inhibitor anemias (ICI-A) are a rare entity which can be potentially life-threatening without prompt identification. The goal of the study is to characterize the presentation, evaluation, and outcomes of ICI therapy in early phase clinical trial setting to guide future research and to develop standardized care guidelines. Retrospective chart review of 333 patients who participated in early phase clinical trials at the University of Texas MD Anderson Cancer Center revealed four cases with ICI-A between 2016 and 2020. We identified a spectrum of four cases which included ICI-related autoimmune hemolytic anemias, hemophagocytic lymphohistiocytosis and thrombotic microangiopathy as a result of combinatory investigational therapies involving ICI. Patient presentation, evaluation, bone marrow pathology, interventions, and clinical course were reviewed. The median time to onset of hematological immune-related adverse events (heme-irAEs) in this retrospective series was 3.5 weeks (2 - 6 weeks). One patient had pre-existing untreated chronic lymphocytic leukemia. Glucocorticoids are an effective first-line treatment in most patients although most patients were not rechallenged but successfully had complete recovery and pursued further non-immunotherapy-based therapies. Cognizance of ICI-A in clinical trial setting is paramount to early recognition of heme-irAEs. Further research is needed to identify and stratify risk factors during clinical trial enrollment and optimal management strategies for immune-mediated hematologic toxicities.

Background: Multiple myeloma (MM) is a genetically heterogeneous disease, with cytogenetic findings that determine disease behavior. Genetic abnormalities can be assessed by fluorescence in situ hybridization (FISH) analysis and/or G-banded karyotyping. The two methods produce unique and overlapping information, and the clinical utility of using both is investigated here.

Methods: Seventy patients diagnosed with MM at a hospital in Southern California were retrospectively reviewed for the FISH and G-banded karyotyping results obtained from bone marrow specimens.

Results: Karyotype was normal in 71% (50/70), abnormal in 27% (19/70), and inadequate in 1% (1/70). Among patients with abnormal karyotype, FISH provided additional information about genetic aberrations in 95% of cases (18/19). Among cases with abnormal FISH, karyotype provided additional information about genetic aberrations in 27% of cases (18/66). When numerical abnormalities were present (detected by FISH and/or karyotype), FISH detected them in 95% (54/57), of which karyotype missed 70% (38/54) of the time. Karyotyping detected numerical abnormalities in 33% (19/57), which FISH missed 16% (3/19) of the time.

Conclusions: Karyotyping and FISH analysis in MM each provide unique information. For most patients, performing both tests together will provide more information than either test alone.