Shruti Kakkar

Thalidomide, a fetal hemoglobin-inducer, can reduce transfusion burden in transfusion-dependent thalassemia (TDT). However, the optimal dosing remains undefined. A prospective, randomized, open-label, multicentric clinical trial was conducted at 4 centres in India to compare the efficacy and safety of thalidomide at 1 mg/kg per day (group 1) with those of 2 mg/kg per day (group 2) in patients with TDT aged ≥12 years. The primary end point was reduction in transfusion requirement at week 24, categorized as good (>50%), moderate (25%-50%), or no (<25%) response. Responders underwent stepwise dose tapering between weeks 25 and 72 to evaluate response sustainability. Safety assessments were performed every 4 weeks. Of the 188 enrolled patients (94 per group), 82.4% completed the week-24 evaluation. The overall response rate was 58.5%, which was significantly higher in group 1 than group 2 (67.1% vs 50.0%; P = .012). Good, moderate, and no response were observed in 20.5%, 37.8%, and 41.6% of patients, respectively, with transfusion independence in 9 patients (5.6%). Clinical benefit was observed within 12 weeks in 71.8% of good responders and 100% of moderate responders. Sustained response was seen in 49% and 57.5% of initial responders in groups 1 and 2, respectively. Adverse effects were mostly grade 1; drug discontinuation because of toxicity was required in 10.6% of participants. These findings suggest that thalidomide at 1 mg/kg per day was noninferior to 2 mg/kg per day in reducing transfusion burden in patients with TDT, with an acceptable safety profile. Low-dose thalidomide appears to be a feasible treatment option in resource-limited settings. This trial was registered at www.ctri.nic.in as CTRI/2022/05/042781.

Introduction Appendicitis in patients with hematological malignancies presents with vague symptoms, thus requiring a high degree of suspicion for early diagnosis and treatment to prevent complications. Objectives The aim of this article was to describe the demographic, clinicoradiological, operative findings, and outcomes in patients with acute appendicitis with underlying hematological malignancies. Materials and Methods A retrospective review of pediatric patients with hematological malignancy who developed acute appendicitis was conducted. Medical records of patients were reviewed for patient demographics, disease status, signs, and symptoms at the time of diagnosis of acute appendicitis, and outcome. The laboratory, radiological, and histological findings were retrieved from the hospital records. Results Six (2.4%) patients developed acute appendicitis over the past 8 years among a total of 254 patients treated for hematological malignancies in the unit. Five patients had underlying acute lymphoblastic leukemia (ALL) and one had acute myeloid leukemia (AML). Of the five patients, three were in postremission consolidation, one each in the delayed intensification and maintenance phase of chemotherapy. The child with AML was on induction chemotherapy for the first relapse at the time of diagnosis. Fever and abdominal pain were the common presenting symptoms. Diagnosis was made on ultrasound abdomen in five patients, and one patient was diagnosed on computed tomography. All patients underwent open appendectomy. Two patients had evidence of appendiceal perforation. Three patients had neutropenia at the time of developing appendicitis and underwent appendectomy regardless of the absolute neutrophil count (ANC). Five patients recovered well, and chemotherapy was restarted within 2 weeks of appendectomy. One patient developed a superficial surgical site infection. and one patient with relapsed AML expired due to refractory septic shock. Conclusion Acute appendicitis in patients with hematological malignancies can present with subtle signs and symptoms. Appendectomy can be safely performed irrespective of the ANC.

As the life expectancy in thalassemia is improving, pain is being recognized as an emerging problem. To document the pain prevalence and severity in patients with transfusion-dependent thalassemia all transfusion-dependent thalassemia patients >10 years of age (n = 165) attending the Thalassemia Day Care Center were assessed for pain prevalence, severity, and its effect on various life activities using the Brief Pain Inventory. Their medical records were reviewed for the presence of various co-morbidities. Pain was reported by 62.4% of participants with 35.2% and 59.4% of participants, reporting pain in the past 1 and 4 weeks respectively. A significantly higher pain prevalence was reported in females (p = .037), patients residing in urban areas (p = .038), and employed participants (p = .038). The commonest sites of pain were the lower back and calves. General activity (p = .02) and enjoyment of life (p = .02) were significantly affected due to pain in patients between 21 and 30 years of age. Female participants reported interference of pain with mood (p = .03). A significant correlation of pain prevalence was found with higher average serum ferritin (p = .015), moderate to severe liver iron concentration (p = .04), and lower levels of 25 hydroxyvitamin D levels (p = .03). Pain is an emerging cause of morbidity in thalassemia. The study found a significant association of pain with modifiable factors such as serum ferritin, LIC, and 25 (OH) vitamin D levels.

Vaccination against SARS-CoV-2 is the most important weapon in the arsenal in the battle against COVID-19. There is concern about an increased risk of adverse effects in patients with transfusion-dependent thalassemia (TDT), which affects vaccine acceptance. A predesigned questionnaire was used to evaluate adverse effects (local/systemic within 90 days after vaccination) in participants >18 years of age with TDT. A total of 100 patients received 129 vaccine doses. The mean age of the patients was 24.3 ± 5.7 years, and M:F ratio of 1.6:1. Covishield (Serum Institute of India) was administered to 89% of the participants, and Covaxin (Bharat Biotech Limited) to 11% of the participants. Adverse effects were documented in 62% of the respondents and were more pronounced after the first dose (52%) compared to the second dose (9%). The most frequent adverse effects were pain at the injection site (43%) and fever (37%). All adverse effects were mild and none of the participants required hospitalization. There were no differences in adverse effects among different vaccines, in the presence or absence of comorbidities, blood groups, or ferritin levels. The SARS-CoV-2 vaccine appears to be safe for patients with TDT.