Search

This article discusses a case study of a 51-year-old woman with systemic lupus erythematosus (SLE) who developed macrophage activation syndrome (MAS) after receiving granulocyte colony-stimulating factor (G-CSF) treatment for neutropenia. MAS is a potentially life-threatening complication characterized by excessive immune system activation. The patient's clinical course strongly suggests that G-CSF administration was the trigger for MAS. The article highlights the need for clinicians to be aware of the potential complications associated with G-CSF administration in SLE patients. [Extracted from the article]

Objective: The diagnostic criteria for secondary hemophagocytic lymphohistiocytosis (HLH) have not been validated in the critically ill adult population. We set out to evaluate the performance of diagnostic criteria and determine the ferritin cutoff in critically ill adults. Design: A retrospective single-center study. Setting and Patients: Patients admitted to intensive care unit between 2008 and March 2010. Data were collected on consecutive patients who had ferritin measured. Charts were reviewed for the diagnostic criteria of HLH and components of Hscore. Measurements and Main Results: A total of 445 patients had a ferritin level measured during the study period. A diagnosis of HLH was made for 10 patients. Having 5 of 6 criteria had a specificity of 97% and a sensitivity of 70%. Hemophagocytosis was found in 41 (47.1%) of 87 bone marrow biopsies. Two hundred thirty-one patients had a ferritin level above 500 ng/dL. When determining the odds of HLH being clinically diagnosed, the optimal cut point for ferritin was 1197 ng/dL. When determining the odds of HLH based on the Hscore, the best cutoff was 143.5 (sensitivity of 90% and specificity of 90%) and patients who had HLH in our study population had an Hscore of 203.8 ± 64.9. Conclusion: In this cohort of critically ill patients, the HLH criteria are specific for HLH but not sensitive. Critically ill patients can have a higher incidence of hemophagocytosis without HLH. A higher ferritin cutoff in combination with 5 other clinical criteria is comparable to the Hscore for the recognition of HLH in the critically ill population. [ABSTRACT FROM AUTHOR]

Acute leukemias of ambiguous lineage (ALAL) are rare hematologic malignancies with poor outcomes. Retrospective studies have suggested that acute lymphoblastic leukemia (ALL) regimens are more effective than acute myeloid leukemia (AML) regimens. We retrospectively examined the effectiveness of the widely-used adult ALL regimen hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyperCVAD) as initial therapy in patients with ALAL at five academic institutions. Twenty-five patients were identified, including 23 with mixed phenotype acute leukemia (MPAL) and two with acute undifferentiated leukemia. Five of 8 tested (63%) had FLT3-ITD and 3 of 25 (12%) were Philadelphia chromosome-positive. The complete remission (CR) rate was 76%, with CR with incomplete count recovery (CRi) in an additional 8%, for an overall response rate of 84%. Median number of cycles to CR/CRi was 1. There were no deaths in the first 30 days. Of the 21 patients achieving CR or CRi, 14 (66%) proceeded to allogeneic hematopoietic stem cell transplantation. With a median follow-up time of 31.6 months, median overall survival for the entire cohort was not reached, and the estimated 2-year survival was 63%. HyperCVAD can be considered an effective and tolerable front-line regimen for patients with ALAL, and warrants further prospective study. [ABSTRACT FROM AUTHOR]

Summary: The day 14 bone marrow aspirate and biopsy (D14BM) is regularly used to predict achievement of complete remission (CR) with induction chemotherapy in acute myeloid leukemia (AML), however its utility has been questioned. Clearance of peripheral blood blasts (PBB) may serve as an early measure of chemosensitivity. PBB rate of clearance (PBB‐RC) was calculated for treatment‐naive AML patients (n = 164) undergoing induction with an anthracycline and cytarabine (7+3) and with detectable PBB at diagnosis. PBB‐RC was defined as the percentage of the absolute PBB count on the day of diagnosis that was cleared with each day of therapy, on average, until D14 or day of PBB clearance. Each 5% increase in PBB‐RC approximately doubled the likelihood of D14BM clearance (OR = 1·81; 95% CI: 1·24–2·64, P < 0·005). PBB‐RC was also associated with improved CR rates (OR per 5% = 1·97; 95% CI: 1·27–3·01, P < 0·005) and overall survival (OS) [hazard ratio (HR) per 5% = 0·67; 95% CI: 0·52–0·87]. African American patients had poorer OS adjusted for PBB‐RC (HR = 2·18; 95% CI: 1·13–4·23), while race was not associated with D14BM or CR rate. PBB‐RC during induction chemotherapy is predictive of D14BM clearance, CR, and OS, and can therefore serve as a prognostic marker for clinical outcomes in AML. [ABSTRACT FROM AUTHOR]

Outcomes and life expectancy for patients with multiple myeloma (MM) have improved substantially over the last two decades with advancements in therapy, including autologous stem cell transplantation and the development of novel agents. All patients had been treated with proteasome inhibitors and/or immunomodulatory agents, 15 (83%) patients with cyclophosphamide and 15 (83%) with melphalan, including all 14 (78%) patients who underwent autologous hematopoietic stem cell transplantation (HSCT). Of the six patients who developed a del(5q) abnormality, two had received lenalidomide maintenance therapy at the time of t-MN diagnosis, and one patient stopped lenalidomide maintenance due to persistent cytopenias 17 months before t-MN was formally diagnosed. Most patients were treated with hypomethylating agent therapy and no patients received intensive chemotherapy for t-MN, likely reflecting the somewhat advanced age of the population, concurrent diagnosis of MM, poor-risk disease characteristics, and the high likelihood of other comorbid conditions. [Extracted from the article]

The article presents a case-report of a 55-year-old male renal transplant patient who developed severe leg pain and "knots" in the lower extremities. It mentions that the diagnosis was Protothecosis caused by Prototheca wickerhamii, a rare disease caused by achlorophyllic algae, prevalent in the environment and particularly risky for immunocompromised individuals.

An article is notes the Cryptic ETV6–PDGFRB fusion in complex rearrangement of chromosomes 1, 5, and 12 due to chromothripsis in a myelodysplastic syndrome/myeloproliferative neoplasm. Topics includes sequencing analysis of chromosome, chromosome abnormalities detection by metaphase cytogenetic analysis, and importance of comprehensive cytogenetic sequencing analysis in accurate diagnosis of hematopoietic neoplasms.

Adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) treated with conventional chemotherapy have dismal outcomes. Novel immunotherapies targeting CD19, including the bispecific T-cell engager blinatumomab and chimeric antigen-receptor T (CAR-T) cells, have revolutionized the treatment of R/R B-ALL. Robust response rates to CAR-T cell therapy after blinatumomab have recently been reported, but it is unknown whether blinatumomab can be effective following failure of anti-CD19 CAR-T cell therapy. Herein, we describe a patient with Philadelphia chromosome-positive B-ALL who relapsed after CD19-directed CAR-T therapy, but subsequently responded to the combination of blinatumomab and the tyrosine kinase inhibitor ponatinib, with the achievement of a complete remission lasting 12 months. [ABSTRACT FROM AUTHOR]

Key Clinical Message Assiduous surveillance for genetic aberrations is necessary in patients on cytotoxic therapies to detect therapy-related myeloid neoplasms (t- MN). Current modalities include metaphase cytogenetics and FISH. Since t- MN may develop abruptly in cytogenetically normal patients, a discussion exploring additional methods such as SNP-array and targeted-deep-sequencing to detect subchromosomal abnormalities is needed. [ABSTRACT FROM AUTHOR]

Differentiation of hematopoietic stem–progenitor cells (HSPCs) into mature blood lineages results from the translation of extracellular signals into changes in the expression levels of transcription factors controlling cell fate decisions. Multiple transcription factor families are known to be involved in hematopoiesis. Although the T-box transcription factor family is known to be involved in the differentiation of multiple tissues, and expression of T-bet, a T-box family transcription factor, has been observed in HSPCs, T-box family transcription factors do not have a described role in HSPC differentiation. In the current study, we address the functional consequences of T-bet expression in mouse HSPCs. T-bet protein levels differed among HSPC subsets, with highest levels observed in megakaryo-erythroid progenitor cells (MEPs), the common precursor to megakaryocytes and erythrocytes. HSPCs from T-bet-deficient mice exhibited a defect in megakaryocytic differentiation when cultured in the presence of thrombopoietin. In contrast, erythroid differentiation in culture in the presence of erythropoietin was not substantially altered in T-bet-deficient HSPCs. Differences observed with respect to megakaryocyte number and maturity, as assessed by level of expression of CD41 and CD61, and megakaryocyte ploidy, in T-bet-deficient HSPCs were not associated with altered proliferation or survival in culture. Gene expression micro-array analysis of MEPs from T-bet-deficient mice exhibited diminished expression of multiple genes associated with the megakaryocyte lineage. These data advance our understanding of the transcriptional regulation of megakaryopoiesis by supporting a new role for T-bet in the differentiation of MEPs into megakaryocytes. [ABSTRACT FROM AUTHOR]

Summary Poly (ADP-ribose) polymerase inhibitors (PARPis) are clinically effective predominantly for BRCA-mutant tumors. We introduce a mechanism-based strategy to enhance PARPi efficacy based on DNA damage-related binding between DNA methyltransferases (DNMTs) and PARP1. In acute myeloid leukemia (AML) and breast cancer cells, DNMT inhibitors (DNMTis) alone covalently bind DNMTs into DNA and increase PARP1 tightly bound into chromatin. Low doses of DNMTis plus PARPis, versus each drug alone, increase PARPi efficacy, increasing amplitude and retention of PARP1 directly at laser-induced DNA damage sites. This correlates with increased DNA damage, synergistic tumor cytotoxicity, blunting of self-renewal, and strong anti-tumor responses, in vivo in unfavorable AML subtypes and BRCA wild-type breast cancer cells. Our combinatorial approach introduces a strategy to enhance efficacy of PARPis in treating cancer. [ABSTRACT FROM AUTHOR]

The classification of haematological neoplasms recently underwent revision, generating two separate schemes-the International Consensus Classification and the fifth edition of the WHO classification. The new division into separate classification systems presents challenges for haematopathologists, haematologists/oncologists and patients. While it is too early to assess the full clinical impact, we sought to identify diagnostic discordance which may arise from applying separate classification schemes in myeloid neoplasia, and particularly in the challenging category of myelodysplastic syndrome/myeloproliferative neoplasms. A review of 64 such cases found 1 case with a significant discrepancy between the WHO and International Consensus Classification systems, and 9 cases with nominal discrepancies. Confusion from the use of conflicting diagnostic terms represents a potential source of patient harm, increased pathologist workload and burnout and erosion of clinician and patient trust., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Massive fetomaternal hemorrhage (FMH) >150 mL is rare and may occur in the absence of high-risk obstetrical events. The significance of FMH in Rh D-negative women is alloimmunization with an increased risk of hemolytic disease of the newborn in subsequent Rh D-positive pregnancies and adverse outcomes for the fetus/neonate. The Kleihauer-Betke (KB) acid elution test is used to quantify fetal erythrocytes in the circulation of Rh D-negative women postpartum and to calculate the dose of Rh immune globulin (RhIG) needed for prophylaxis against alloimmunization. In this case, the KB stain unexpectedly revealed 4.5% fetal cells, a finding consistent with a massive FMH of 225 mL, in the absence of a predisposing cause and clinical signs in the infant. This case underscores the importance of FMH quantification in all Rh D-negative women with Rh D-positive fetuses, uncomplicated pregnancies, and healthy newborns. We discuss factors that can affect KB test performance and caveats in interpretation.

In practice, cases of therapy-related myelodysplastic syndrome (t-MDS) are often classified according to morphologic schemes used for de novo MDS. However, there are few data addressing the appropriateness of such classification. We studied 155 patients with therapy-related acute myeloid leukemia (t-AML)/t-MDS to determine whether subclassification by the World Health Organization (WHO) criteria for de novo MDS provides prognostic information in t-MDS. In addition, we assessed whether cytogenetic stratification by the International Prognostic Scoring System (IPSS) guidelines or karyotypic complexity was prognostically important. We found no differences in median survival times among patients classified into the different WHO subgroup of MDS or according to their bone marrow blast percentage; our results indicate a uniformly poor outcome in t-MDS regardless of morphologic classification. However, significant survival differences correlated with cytogenetic stratification according to IPSS guidelines and/or karyotypic complexity. We found only a borderline difference in median survival of patients with an initial t-MDS diagnosis compared with patients with an initial t-AML diagnosis.

Gelatinous marrow transformation (GMT) is an uncommon and poorly recognized condition characterized by deposition of seromucinous gelatinous material in the bone marrow stroma. Forty-three cases of GMT were studied in a period of 4 years. There was male preponderance. Fourteen cases were in pediatric age group (less than 12 years). Majority of patients had a preceding history of anorexia, malnutrition and chronic debility. All the patients had anemia. Bone marrow biopsy revealed focal or diffuse GMT. Bone marrow aspirate showed metachromatic dense mucoid material with a few entrapped hematopoietic cells on Giemsa staining. The gelatinous material stained with alcian blue at pH 2.5.

In a retrospective study, 49 bone marrow biopsies (BMB) of patients with multiple myeloma (MM) were studied for its role in diagnosis and to determine histological parameters of prognostic significance. Sections were analyzed by 2 observers and classified according to: 1. Cytological grading according to differentiation of the neoplastic cells as plasmacytic, pleomorphic and plasmablastic. 2. Volume of infiltration: quantitating the percentage of myeloma cells in the biopsy. 3. Pattern of neoplastic infiltration. The overall marrow cellularity, presence of marrow fibrosis, micro-osteolesions and normal haematopoeisis were also studied. The bone marrow biopsy (BMB) was diagnostic for myeloma in five cases, where the aspirates were hypocellular: four had early myeloma and one had extensive marrow fibrosis. The pattern of infiltration was interstitial in 19 cases (39%), nodular in 19 cases (39%), and diffuse in 11 cases (22%). In majority of the cases (49%), the cell type was plasmacytic (24 cases), plasmablastic in 10 cases and pleomorphic in 15 cases. All cases of poorly differentiated cell type (plasmablastic) had a diffuse or nodular pattern of infiltration, whereas majority of the well-differentiated cell type had an interstitial pattern. The plasma cell burden in biopsy i.e the volume of infiltration was <10% in 8 cases, <50% in 19 cases and >50% in 22 cases and was used for histological staging of MM. Fibrosis was present in 30% of cases. Follow up was available in 11 cases, and cases with poorly differentiated myeloma, diffuse pattern of infiltration and dense fibrosis had survival less than one year. Cases of well differentiated myeloma, interstitial pattern of infiltration and plasma cell load less than 20% with absence of fibrosis had a more than 5-year survival. Different series have quoted that all these histological parameters provide valuable prognostic information, wherever other modalities like beta 2 microglobulin and IL-6 levels, etc are not available. The effects of therapy can also be monitored by sequential biopsies.