Background: Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by increased platelet destruction and impaired platelet production. Over the past decade, use of thrombopoietin receptor agonists (TPO-RA) is steadily rising in ITP. Aims: In this study, we explore the clinical profile of ITP patients on TPO-RA therapy, response rates to TPO-RA therapy, and analyze various factors that can predict outcomes in one of the largest public-sector teaching hospitals in India. Methods: This retrospective observational study included consecutive patients diagnosed with ITP and initiated on TPO-RA therapy (Romiplostim and Eltrombopag) in our clinic from January 1, 2016, to December 31, 2021. Response was defined according to standard international criteria. Results: Over the past six years, 166 patients were initiated on TPO-RA therapy and had a total of 183 treatments (92 eltrombopag, 74 romiplostim, and 17 trailed on both). The median age in our cohort was 28.5 years (range, 1.5-70 years). Pediatric cohort (age < 18 years) included 57 patients. Almost half (N=93; 56%) of the patients had chronic ITP prior to TPO-RA initiation. Baseline characteristics were shown in Table 1. Response rates were significantly higher in the romiplostim group when compared to the eltrombopag group (91% vs. 60%; p<0.001) in the pediatric cohort, which was not observed in the adult cohort (77% vs. 84%; p=0.28). Response rates were significantly higher in the pediatric cohort when compared to the adult cohort in the romiplostim group (91% vs. 77%; p = 0.008); however, adults responded better in the eltrombopag group (84% vs. 60%; p<0.001). There was a significant reduction in bleeding manifestations at 1 month when compared with baseline (20% vs. 61%; p<0.001). On univariate analysis, prior splenectomy was a predictor of poor response to TPO-RA therapy. However, on multivariate analysis, age, sex, ITP duration, prior splenectomy, prior lines of therapy were not predictive of response. Adverse events: Thrombocytosis was noted in 12 (7%) patients with no evidence of thrombosis, and 2 (1%) patients progressed to myelodysplastic syndrome. Of the 17 patients who were trailed on both therapies, 6 (3.5%) patients failed both TPO-RA therapies. Among the 54 (31%) patients who discontinued therapy, 11 (6.6%) patients achieved durable response off treatment. The median follow-up duration was 13 months (range, 0.8-79 months). Image:Summary/Conclusion: Response rates to TPO-RA therapy in our cohort are consistent with those reported from the West. We observed that response rates were significantly higher in our pediatric cohort when compared to our adult cohort.
Dear Editor, Renal diseases associated with monoclonal gammopathy without symptomatic multiple myeloma (MM), Waldenstrom’s macroglobulinemia (WM), or chronic lymphocytic leukemia (CLL) are increasingly known.[1] Many of these patients have a small clonal population of plasma cells (PCs) or B cells. The International Kidney and Monoclonal Gammopathy Research group (IKMG) introduced the term monoclonal gammopathy of renal significance (MGRS) in 2012.[1] The MGRS includes monoclonal gammopathy of uncertain significance (MGUS), smoldering MM, smoldering WM, monoclonal B-cell lymphocytosis (MBL), CLL, and low-grade B-NHL associated with renal involvement.[1,2] The diagnosis of MGRS is based on renal biopsy and monoclonal protein identification. B-cell or PC clone identification is paramount for a clone-directed therapy for long-term hematologic response.[2] As these clones are small, a highly sensitive technique like flow cytometry (FCM) should be used to identify clonality.[3] It is important to identify MGRS as these patients do not respond well to immunosuppressive therapy, have a high rate of recurrence post renal transplantation, and can progress to corresponding hematological malignancy.[4] We are describing two cases of MGRS where we could confirm the presence of a small clonal PC population using FCM. The case characteristics are listed in Table 1.Table 1: Clinical characteristics of the two cases of MGRSFCM for PCs was performed on the bone marrow (BM) sample collected in ethylenediaminetetraacetic acid (EDTA). The sample was lysed and staining done using a panel of antibodies against CD38-APC-Cy7, CD138-PE, CD45-PerCP-Cy5.5, CD19-PE-Cy7, CD27-FITC, CD81-FITC, CD56-APC, CD117-APC, intracellular anti-kappa-APC, and anti-lambda-FITC. Specimens were acquired using three-laser BD FACS Canto-II (BD Biosciences, San Jose, CA, USA) and analyzed on BD FACS Diva software version 8.0.1. Case 1 showed 0.2% PCs on CD38, CD138, CD45, and side scatter (SSC) gating. Of these, half, that is, 0.1% PCs, showed an abnormal immunophenotype (CD56+/CD19−/CD81−/CD45) with a κ-restriction [Figure 1]. Case 2 showed 0.9% PCs on CD38, CD138, CD45, and SSC gating, including 0.8% λ-clonal PCs with an abnormal immunophenotype (CD56+/CD19−/CD27−/CD45 partial loss).Figure 1: Plasma cell immunophenotyping in case 1: plasma cell gating on CD38/CD138 (plot 1), plasma cell gate refinement on CD38/CD45 (plot 2), abnormal PCs (blue), normal PCs (orange), and mature lymphocytes (green) on CD19/CD45 (plot 3), CD56 expression with CD81 loss in abnormal PCs, while the normal PCs express CD81 and are negative for CD56 (plot 4), κ-restricted abnormal PCs and polyclonal B cells (purple) (plot 5), polyclonal normal PCs (orange) and B cells (purple) (plot 6). PC = plasma cellIn both cases, clonality in BM could be proven on FCM, whereas immunohistochemistry showed a polyclonal population. Clonal identification is important as same renal lesions can be found in different hematological disorders and treatment varies depending upon the type of clone (B cell/PC).[2] Immunohistochemistry could be useful only when a major PC clone is present and polyclonal population is lacking.[2] However, immunohistochemistry has low sensitivity when less number of abnormal PCs are admixed with polyclonal population.[3] FCM has the advantage of studying a large number of cells and simultaneous measurement of multiple antigenic expressions. Sensitive FCM can detect monoclonal PCs at a sensitivity of 10 − 4–10 − 6 and can discriminate between MGUS and MM. The number of residual polyclonal PCs is a useful discriminating marker between MGUS and MM.[5] MGUS usually has more than 5% normal plasma cells (NPCs) within total BM PCs (both our cases showed NPCs of 50% and 20%, respectively).[5] To conclude, characterization and clonality identification of PCs or B cells in BM by FCM is a must in cases of MGRS as it is highly sensitive and guides in appropriate decision-making to guide correct therapy. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
Congenital dyserythropoietic anemia (CDA) are a diverse category of heritable anemia. The causative genetic abnormalities interfere with the normal developmental process of erythrocyte maturation inside the bone marrow. As a consequence, red blood cell precursors die prematurely in the marrow (ineffective erythropoiesis) and the altered mature RBCs that come to peripheral blood have reduced survival. Due to relative rarity and resemblance to other common disorders, the diagnosis is often delayed. Apart from having symptoms related to anemia and chronic hemolysis, most of these patients suffer from complications of iron overload even if not transfusion dependent. Classically, 3 major categories of CDAs have been described (I, II, III). Other described CDA variants are rare. With easier accessibility and widespread availability of genetic testing, it is possible to make molecular diagnoses for most cases. The diagnosis can be accelerated by targeted next-generation sequencing. There's no unifying theory explaining the pathogenesis behind the disease causation. In-depth understanding at the cellular level has clarified the multifactorial pathologic process. In this review, we describe the epidemiology, pathophysiology, clinical features, and management options available for CDA. We also summarize a brief report of 17 CDA patients diagnosed and treated at our center in the last 5 years, with their genetic findings, wherever available.
Treatment of acute promyelocytic leukaemia has emerged as a major success in hemato-oncology. While literature from the developed world boasts of outstanding outcomes, there is a paucity of data from the developing world. This study aimed to assess complications and outcomes of acute promyelocytic leukaemia in a resource-constrained setting.We retrospectively collected data from patients diagnosed with APL from January 2016 to December 2020.Sixty-four patients were treated-32 in both the Sanz high and low-risk groups. In the Sanz low-risk group, 12.5% of patients received ATRA with daunorubicin and 81.25% received ATRA with ATO. In the Sanz high-risk group, 18.8% of patients received ATRA with daunorubicin, 34.3% received ATRA with daunorubicin and ATO while 40.6% received ATRA with ATO. 56.25% of patients developed differentiation syndrome. The incidence was higher in Sanz high-risk group as compared to Sanz low-risk group. 57.4% of patients had an infection at the time of presentation. 62.5% of patients developed neutropenic fever during treatment. 17.2% of patients developed pseudotumor cerebri. The 4-year EFS and OS were 71.25 and 73.13%, respectively. Sanz low-risk group had a better 4-year EFS and OS as compared to the Sanz high-risk group. Haemoglobin at presentation and Sanz high-risk group were associated with poorer outcomes with a hazard ratio of 0.8 and 3.1, respectively. Outcomes in high-risk patients were better with the use of ATRA + ATO + daunorubicin.In the Indian population, APL patients have a high incidence of differentiation syndrome, pseudotumor cerebri, and infections during induction. CR, EFS, and OS compared to the developed world can be achieved with optimal therapy. Low haemoglobin at presentation and Sanz high-risk group were associated with poorer outcomes. ATRA, ATO, and daunorubicin combination is the preferred protocol for treating high-risk patients.
All trans-retinoic acid (ATRA) is a targeted therapy, used in Acute Promyelcytic leukemia (APL) and causes the abnormal promyelocytes to differentiate in to mature leucocytes, however their clearance in vivo is not known.with hemophagocytosis, but sometimes one may find phagocytosis of differentiated cells by histiocytes without the overt manifestations of hemophagocytic syndrome.We report a case of APL showing differentiated cells being phagocytosed by marrow histiocytes while patient was getting ATRA therapy.
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