ABSTRACT
Background: Infections contribute to an early mortality risk of 15 percent in newly diagnosed multiple myeloma(NDMM) cases. There is a limited literature on the type of infections in fully vaccinated NDMM patients. Aims: To study epidemiology, clinical profile and predictors of infection in NDMM who are immunised against pneumococci and influenza. Methods: NDMM patients were prospectively studied for 6 months for the pattern of infections . All patients were vaccinated with pneumococcal and Influenza vaccine at diagnosis. PJP prophylaxis and fluconazole prophylaxis was given for patients receiving high dose steroids while acyclovir was given to all. Infections were classified as microbiologically defined, clinically defined and fever of unknown focus according to definitions published by the International Immunocompromised Host Society. Severity of infections were graded according to the NCI CTCAE Ver5. Results: Forty-eight NDMM patients with a median age 55 years comprising of 26 males and 22 females were enrolled. Renal involvement was noted in 42% of enrolled patients and two third of them required renal replacement therapy. ISSIII and R-ISS III were 70.8 % and 62.5 % respectively. 85% had poor performance status(ECOG ≥2) at baseline. RVD was the most common regimen (37%)used. 6 patients received daratumumab based regimen. Treatment response of atleast VGPR was seen in 97 % of NDMM patients. A total of 19 episodes of infections were observed during 6 months. All episodes of infections were reported in the first 45 of myeloma diagnosis(Median 6 days;Range 0-45). Ten of these episodes of infection were diagnosed during the initial evaluation for myeloma defining events. Microbiological diagnosis was possible in 63 %. Commonest infectious agent was COVID 19(n=8) followed by Gram negative bacteria (n=5) viz E.coli and Klebsiella pneumoniae . None of the eight patients who developed COVID 19 infection had received COVID vaccine as they antedated the operationalisation of national guidelines for immunisation. Respiratory and the urinary tract were the most common focus of infection. All critically ill COVID patients succumbed to progressive respiratory failure and all patients with mild and moderate COVID illness recovered uneventfully. Early mortality in our cohort of forty eight patients was twenty percent(n=10). Three fourths of infections in our cohort were Grade≥3 severity. A total of seven deaths were attributable to infectious diseases in this cohort of NDMM patients. Imune paresis was seen in eighty four percent of patients at diagnosis. On follow up at 6 months;immune paresis had persisted in only thirty seven percent. Regression analysis of variables with odds of infection is shown in Table 1 Baseline BMI<18.5 kg/m2;albumin<3g/dl and ISS or R-ISS stage ≥ 2 was found to be have statistically significant odds of predicting infection risk in the cohort of patients. The choice of myeloma regimen, presence of high risk cytogenetics and response to therapy did not correlate with increased odds of infection in our cohort. Summary/Conclusion: Conclusion In this prospective study of NDMM patients vaccinated against pneumococci and influenza at baseline;infection attributable early mortality was 14.5 %. Advanced stage of presentation, hypoalbuminemia and baseline BMI < 18.5 kg/m2 correlated with increased odds of infection. COVID vaccination and COVID appropriate behavioural practices may mitigate COVID related outcomes including deaths in myeloma patients.
ABSTRACT
Introduction: Acute lymphoblastic leukemia in adults represent amajor therapeutic challenge even in modern era. Constantly evolvinggenomics has led to a better risk stratification and prognostication.Aims &Objectives: Here we present a novel mutation in calreticulingene in a patient with Precursor B lineage Acute lymphoblasticleukemia.Materials &Methods: A 19 year old boy presented with fever,jaundice and pancytopenia. Initial investigation revealed a hemoglobin of 5.8 g/dl with a total leukocyte count of 700 cells/mm3 andplatelet count of 11,000/mm3. Differential count showed 95% lymphocytes and 5% neutrophils and no blasts with mildanisopoikilocytosis on PBF. Bone marrow biopsy demonstartedreduction granulocytic and erythroid lineage with adequatemegakaryocytes and occasional collections of immature appearingcells, whose charcter was not able to be definitely ascertained. PETCT showed FDG avid lymph nodes on both sides of diaphragm, withPET guided biopsy was suggestive of non specific lymphocyticinflammatory infiltrate. A diagnosis of hemophagocytic lymphohistiocytosis (HLH) was made according to HLH 2004 criteria (Fever,cytopenias, hypertriglyceridemia, splenomegaly and elevated serumferritin levels). However workup for primary HLH and primaryimmune deficiencies were negative.Clinical exome sequencing forprim was postive for mvk transcript (c.808G >A). He was treatedwith IVIG and short course steroids. Repeat bone marrow was normocellular with mild erythroid prominence and adequaterepresentation of granulocytic and megakaryocytic lineage elements.He was under regular follow up thereafter.Result: He developed mild Covid illness a month after discharge. Amonth after recovery from illness, he presented with easy fatiguabilityand pancytopenia (Hb: 7.1 g/dl, TLC: 900 cells/mm3 and Plateletcount: 1.46 lakhs) with presence of occasional blast in PBF. Repeatbone marrow was markedly hypercellular with 76% blast.Megakaryocytes were relatively preserved. On flow cytometry, blastswere positive for CD 10, CD 19, CD 20, cyto CD 79a, CytoCD22, CD34, CD 45, HLA DR and TDT and negative for MPO CD 2 CD 3 CD13 aand CD 33 consistent with Precursor B Lineage acute lymphoblastic leukemia. Multiplex RT-PCR for recurrent geneticabnormalities (ALL) were negative. A never reported CALR (TYPE1) mutation was found in this patient. CALR plays an important rolein cell proliferation, apoptosis and immune responses. Patient wastreated with modified BFM regimen and Rituximab, attained CR postinduction and currently in consolidation phase of therapy.Conclusions: CALR mutation has never been reported before in acase of acute lymphoblastic leukemia. Long term follow up of patient is required to conclude whether the novel mutation has prognostic andtherapeutic implications.