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Eltrombopag has shown efficacy in the treatment of thrombocytopenia and poor graft function (PGF) after allogeneic hematopoietic cell transplantation (HCT) in retrospective observational studies, but is not approved for this indication. The cost of this drug is also a major concern in publicly funded health care systems. We collected data about patients who received eltrombopag for thrombocytopenia or PGF after HCT. Post-HCT thrombocytopenia, PGF, and eltrombopag response were defined as per previously published criteria. Primary outcome was treatment efficacy and secondary outcome was cost comparison between estimated treatment cost prior to and after initiation of eltrombopag. Seventeen patients (males 70.6%; median age = 58) received eltrombopag. Isolated thrombocytopenia was present in 11.8% (n = 2) patients while PGF was present in 88.2% (n = 15) of patients. After 8 weeks of treatment at the maximum dose of 150 mg orally daily, overall response rate (ORR) was seen in 76.5% (13/17) of patients: complete response (CR) in 10/13 patients and partial response (PR) in 3/13 patients. The use of eltrombopag was associated with an overall decrease in the total weekly care costs (5021 vs 2,524 CA$; P = 0.04). Thus, Eltrombopag is an efficacious and possibly cost-effective therapy for thrombocytopenia and PGF after allogeneic HCT.

Background: Most data on autologous hematopoietic cell transplantation (auto-HCT) in myeloma are based on the use of innovator formulation of melphalan. Comparative bioequivalence and efficacy studies of generic melphalan are lacking. Methods: In this retrospective study, we report long-term outcomes of auto-HCT in myeloma using innovator (Alkeran, Aspen Pharma; n = 41) and generic melphalan (Alkacel, Celon Labs, India; n = 55) formulations. All consecutive patients at a single center from the period 2011–2018 were included. Results: The median follow-up in the innovator and generic groups was 61.7 and 32.5 months, respectively. Both groups were matched for age, sex, stage, and myeloma response. There were significantly more patients in the innovator melphalan group who were administered melphalan at a reduced dose at physician discretion (26.8% vs. 3.6%, p = .001). There were significantly more patients with grade 3 or higher mucositis (68.3% vs. 38.1%, p

Objective/Background: Unsuccessful cytogenetic (US) analysis at baseline has been reported to be a poor prognostic feature in patients with acute myeloid leukemia (AML). We conducted this study to examine the prognostic impact of UC/inconclusive cytogenetic analysis on outcomes in patients with AML undergoing allogeneic hematopoietic stem cell transplantation (Allo HSCT). Methods: We retrospectively analyzed all adults undergoing Allo HSCT for AML from January 2011 to August 2019. Patients with any documented cytogenetic abnormalities were excluded. Baseline characteristics and transplant outcomes were compared between patients with normal cytogenetics and those with UC. Results: Overall, 243 AML patients (median age, 55 years; 55.1% female) were included. UC were reported in 79 patients, whereas 164 patients had a normal karyotype. The two groups were similar to each other in terms of baseline demographics, treatment received, and transplant related variables. There was no difference between patients with UC and normal cytogenetics in terms of relapse-free survival (66 months vs. 42 months, p = .53) or overall survival (OS; 77 months vs. 76 months, p = .72). Survival parameters remained similar even in subgroup analysis based on NPM1 and FLT3 mutation status. Significant predictors of OS after Allo HSCT in AML patients with UC were increased age at time of Allo HSCT (hazard ratio [HR] = –1.049; 95% confidence interval [CI], 1.005–1.095), favorable (NPM1Mut/FLT3wt) mutation profile (HR = 0.11; 95% CI, 0.01–0.84), neutrophil engraftment

Patients with amoebic liver abscess (ALA) may require percutaneous catheter drainage (PCD). Once the PCD output is substantially reduced or has ceased along with clinical recovery, residual collections on radiological evaluation may concern the treating physicians. The prevalence and significance of such collections is unknown, and the subsequent approach how to tackle them is unclear. Consecutive patients with one or more uncomplicated ALAs requiring drainage were prospectively enrolled from 3 hospitals and managed based on a standard approach. Catheter removal was attempted after the patients fulfilled all 4 of the following criteria: disappearance of abdominal pain, absence of fever for at least 48 h, an improving trend of TLC (documented on 2 consecutive reports), and catheter drain output of

Therapy related acute leukemia consists of a unique subset of acute leukemia with an increased frequency of high risk cytogenetic and molecular abnormalities, dismal response to therapy, higher relapse rates and poor overall survival. Therapy related acute myeloid leukemia (t-AML) is a better defined disease entity than therapy related acute lymphoid leukemia (t-ALL). However, in recent times, t-ALL is also being increasingly recognized and extensively studied. Therapy related acute myeloid leukemia is usually classified together with therapy related myelodysplastic syndrome. However, the management of these two diseases maybe different regarding needs of induction chemotherapy and eligibility for upfront allogeneic hematopoietic stem cell transplantation (Allo HSCT). There is also evidence regarding differences in prognosis and outcomes between these two entities. Allo HSCT offers a potential for cure in t-AML and t-ALL. However, existing literature on the same is confounded by inclusion of t-MDS and secondary acute leukemias. Here we review the current evidence on the outcomes and predictors of outcomes of Allo HSCT in the management of therapy related acute leukemias. We also shed light into the under-representation of therapy related leukemias in clinical trials. This stresses the need for prospective trials incorporating measurable residual disease monitoring and sequential next generation sequencing based genomic data for accurate prognostication and management of therapy related acute leukemia.

Introduction Therapy-related acute lymphoblastic leukemia (t-ALL) is an increasingly recognized subset of therapy-related acute leukemia. There are limited data on the role of allogeneic hematopoietic stem cell transplantation (HSCT) in t-ALL. Recent reports suggest comparable outcomes of t-ALL with de novo ALL after HSCT. Patients and methods We retrospectively reviewed all patients of t-ALL who underwent HSCT at our center. Patients were analyzed for prior malignancy, therapy, time to diagnosis of t-ALL, clinical, laboratory characteristics, transplant details, relapse-free survival (RFS), and overall survival (OS). Results Eighteen patients (M:F ratio 1:1; Median age 44 years) underwent HSCT for t-ALL. Median latent period from primary malignancy to t-ALL was 44.8 months. 11q23 rearrangement and t(9;22) were present in 33.3% and 22.2% patients, respectively. Stem cell donors were matched related, matched unrelated, and haploidentical in 27.8% (n = 5), 55.6% (n = 10), and 16.7% (n = 3) patients, respectively. Five patients died before D+ 100 (27.8%). Estimated 2-year RFS and OS were 47.1% and 51.8%, respectively. We did not find any pretransplant and post-transplant risk factors that were predictive of improved OS or RFS after multivariate analysis. Conclusions Allogeneic HSCT outcomes in t-ALL were comparable to HSCT outcomes in de novo ALL. Multicenter studies with more patients and longer follow-up may provide factors affecting outcome and survival.

BACKGROUND Allogeneic hematopoietic stem cell transplantation (allo-HCT) is currently the only curative treatment for patients with chronic lymphocytic leukemia (CLL). METHODS We analyzed the outcomes of 93 patients (median age: 52 years) who underwent allo-HCT at our center between 1989 and 2019. RESULTS After a median follow-up of 35 months, relapse was observed in 15.1% (n = 14) patients. The estimated 2-year non-relapse mortality, relapse-free survival, and overall survival (OS) were 38.1%, 54.2%, and 58.7%, respectively. The ECOG performance status ≥ 2 (hazard ratio [HR]: 4.1; p = .001) and use of total body irradiation (in a myeloablative conditioning regimen; HR: 2.64; p = .005) were predictive of poor OS after multivariable analysis. The occurrence of sinusoidal obstruction syndrome/veno-occlusive disease post-transplant was associated with poor survival (p = .001). CONCLUSION Although the use of kinase and bcl2 inhibitors may result in a decrease in the number and need of transplants, allo-HCT remains a viable option in selected patients with high-risk CLL and good performance status.

The COVID-19 disease, which was declared as a pandemic by WHO on the 11th of March 2020 has to date, infected over 38 million people worldwide. The medical community was mostly unprepared for the i...

Recent studies in iron-depleted women have challenged the current approach of treating iron-deficiency anemia (IDA) with oral iron in divided daily doses. Alternate day dosing leads to more fractional absorption of iron. In this randomized controlled trial, we looked at the efficacy and safety of alternate-day (AD) versus twice-daily (BD) oral iron in all severity of IDA. Total of 62 patients were randomized, 31 patients in BD arm received 60 mg elemental iron twice daily while 31 patients in AD arm received 120 mg iron on alternate days. The primary endpoint of 2 g/dl rise in hemoglobin was met in significantly more patients in the BD arm at 3 weeks (32.3% vs. 6.5%, p < 0.0001) and 6 weeks (58% vs. 35.5%, p = 0.001). There was a significant rise in the median hemoglobin at 3 (1.6 vs. 1.1, p = 0.02) and 6 weeks (2.9 vs. 2.0 g/dl, p = 0.03) in the BD arm. However, the median hemoglobin rise in the AD arm at 6 weeks was not significantly different than the BD arm at 3 weeks. Alternate-day dosing for 6 weeks and twice-daily dosing for 3 weeks resulted in the provision of the same total amount of iron. There were more reports of nausea in the BD arm (p = 0.03). In conclusion, the choice of twice-daily or alternate-day oral iron therapy should depend on the severity of anemia, the rapidity of response desired, and patient preference to either regimen due to adverse events. Trial Registration: CTRI reg. no. CTRI/2018/07/015106 http://ctri.nic.in/Clinicaltrials/login.php.

Celiac disease (CD) is known to be associated with several autoimmune disorders. We studied the prevalence of subclinical CD among patients with immune thrombocytopenia (ITP) as compared to general population. Cases of primary ITP between the age group of 18–60 years were studied. Besides clinical examination, all patients underwent serology testing for tissue transglutaminase antibody (tTG) IgA and anti-endomysial antibodies IgA. The diagnosis of CD was made if both antibodies were positive. Healthy subjects acted as controls and underwent serological testing for tTG IgA. Seventy-nine primary ITP and 316 healthy subjects underwent serology testing for CD. Four patients of primary ITP (4/79) were positive for both serology as compared to 2 (2/316) healthy controls [odds ratio 8.37 (CI 1.50–46.47, p

Background/Objective Existing literature on allogeneic hematopoietic stem cell transplantation (allo-HSCT) in therapy-related acute myeloid leukemia (t-AML) is confounded by the inclusion of patients with secondary AML and t-MDS. We aim to report our 20-year experience of HSCT in t-AML. Methods We retrospectively reviewed patients with t-AML who underwent HSCT. Patients were analyzed for prior malignancy, therapy, time to diagnosis of t-AML, transplant details, relapse-free survival (RFS), overall survival (OS), and predictors of outcomes. Results In total, 68 patients (59.9% female; median age, 56.5 years) underwent HSCT. Acute and chronic graft-versus-host disease (GVHD) occurred in 39 (57.4%) and 23 (33.8%) patients, respectively. Cumulative incidence of relapse, nonrelapse mortality, RFS, and OS at 2 years were 17.9%, 34.5%, 47.6%, and 49.3%, respectively. Significant predictors of reduced OS were presence of 11q23 rearrangement (hazard ratio [HR], 3.24), using induction regimens other than FLAG-Ida or 7 + 3 (HR, 3.65), haploidentical donors (HR, 3.48), Eastern Cooperative Oncology Group performance status 2 or higher (HR, 5.83), and using cyclosporine A–methotrexate as GVHD prophylaxis (HR, 2.41). A significant decrement in survival was seen with an increasing number of any of these prognostic factors. Conclusion Outcomes of t-AML are satisfactory after allo-HSCT. Patients with t-AML with good-risk karyotypes, good performance status, having HLA-matched donors, and receiving intensive induction regimens have better outcomes after HSCT.

Both innovator and generic imatinib are approved for the treatment of Chronic Myeloid Leukemia-Chronic phase (CML-CP). Currently, there are no studies on the feasibility of treatment free remission (TFR) with generic imatinib. In a single center prospective Generic Imatinib Free Trial - in -CML-CP (GIFT-in-CML-CP) study, twenty-six patients on generic imatinib for more than 3 years and in sustained deep molecular response (BCR ABLIS

Glucose‐6‐phosphate dehydrogenase (G6PD) deficiency is an inherited genetic disorder caused by red cell enzymatic defects and is associated with haemolytic crisis when patients are exposed to oxidative agents (fava beans, drugs, infections). Hydroxychloroquine is suspected to trigger haemolytic crisis in G6PD‐deficient patients, and off‐label administration of this drug to patients infected with the novel coronavirus (SARS‐CoV‐2) could cause concern. We report here the first case of severe haemolytic crisis in a patient with G6PD deficiency, initiated by severe COVID‐19 infection and hydroxychloroquine use. With worldwide spread of COVID‐19, especially in regions with a high prevalence of G6PD deficiency, our case should alert physicians to this possible correlation.

Donor safety is of prime importance in allogeneic hematopoietic cell transplantation. The Worldwide Network for Blood and Marrow Transplantation (WBMT) standing committee on donor issues has issued a consensus statement regarding suitability criteria for related adult donors. This committee recommends that donors with a history of immune-mediated glomerulonephritis and abnormal urine tests should preferably undergo bone marrow harvest, to avoid the theoretical risk of granulocyte colony-stimulating factor (G-CSF) induced immune flare-up. We discuss here a unique situation where a related donor with a history of IgA nephropathy (IgAN) insisted on a peripheral blood stem cell harvest. We propose a management plan for this situation, which posed challenges about donor suitability.

Thrombocytopenia is often a source of concern for physicians and patients alike and is one of the commonest reasons for a hematology consultation. Through this study, we wish to ascertain the different etiologies which should be kept in mind by a hematologist when a consultation for thrombocytopenia is sought. We assessed the etiology & clinical features of thrombocytopenia seen on consultative hematology calls for patients admitted in the general ward of a tertiary care hospital. 88/277 hematology consultations taken over a course of 2 months were for thrombocytopenia. The median age of these patients was 30 years, 62.5% were female, and median platelet of 40,500/µL (1000–112000). Mild, moderate & severe thrombocytopenia was seen in 6.8%, 27.3% and 65.9% respectively. 50% of patients had a primary hematological diagnosis. Immune thrombocytopenia (ITP) was the commonest diagnosis (38.6%). Bleeding manifestations were present in 48.9% patients with 20.5% having a major bleed. One third of hematology consultations in the general ward and emergency of a tertiary care hospital are for thrombocytopenia. Almost in half, the etiology of thrombocytopenia is related to a primary hematological disorder. This information should help in decision making of use of appropriate resources.

Background - Allogeneic Hematopoietic Stem Cell transplant (HSCT) is the only potential curative treatment in patients with chronic myelomonocytic leukemia (CMML). Predictors of outcomes of Allo HSCT in CMML vary across studies and include achievement of complete remission, year of transplant, splenomegaly, performance status, prognostic scores and graft source. Inclusion of patients who progressed to AML also confounds outcome comparisons in many previous studies. The factors predictive of outcome with the use of newer GVHD prophylactic regimens including anti thymocyte globulin (ATG) and post-transplant cyclophosphamide (PTCy) are largely unknown. We report our experience of HSCT in CMML in remission and try to identify predictors of survival. Methods - We retrospectively reviewed all cases of CMML who underwent HSCT at our centre from January 2005 to June 2020. We collected data for demographic characteristics, cytogenetic and molecular characteristics of CMML, prior CMML treatment, latent period before transplantation, prognostic scores, transplant details (donor details, conditioning regimens, GVHD prophylaxis) as well as post-transplant complications (transplant related mortality, occurrence and severity of acute and chronic GVHD, CMV and EBV reactivations). Primary outcome evaluated was overall survival and secondary outcomes were relapse rate and relapse free survival (RFS). Cox-proportional hazards regression model was used to identify predictors of survival. Results - A total of 31 patients underwent allogenic HSCT for CMML during the study period. 58% (n=18) were males. Patients who had progressed to AML were not included in this study. Median age at HSCT was 61 years (range 33-71). Baseline characteristics are summarized in Table 1. Cytogenetic analysis was abnormal in 43.3% (n=13) with high risk cytogenetics (deletion 17p, complex cytogenetics) present in 12.9% (n=4) patients. The median time from diagnosis of CMML to transplantation was 12.4 months. Pre transplant performance status was ECOG Score 0-1 in 73.3% (n=22) patients and Score≥ 2 in 26.7% (n=8) patients. Donors were matched related (MRD), matched unrelated (MUD) and mismatched unrelated MMUD) in 32.3% (n=10), 54.8% (n=17), 12.9% (n=4) transplants respectively. Donor age was significantly lower in MUD when compared to related donors (Median donor age 27 vs 54.5 years; p=0.01). Conditioning regimens used were myeloablative in 25.8% (n=8) and reduced intensity in 74.2% (n=23) patients. The most common GVHD prophylactic regimens used were ATG-PTCy based in 45.2% (n=14) patients. Transplant related mortality (TRM) was 9.67% (n=3). Acute and chronic GVHD occurred in 38.7% (n=12) and 48.4% (n=15%) respectively. After a median follow-up of 12.1 months, 25.8% (n=8) patients relapsed. Estimated 1-year Relapse free survival (RFS) and overall survival (OS) were 52.4% and 59% respectively (Figure 1A). Having a 10/10 MUD was the only significant predictor for improved OS (median OS in MUD vs MRD vs MMUD = 140 vs 10 vs 4 months; p=0.014) and RFS (median RFS in MUD vs MRD vs MMUD = 140 vs 9 vs 2.3 months; p= 0.01) after Cox Regression Analysis (Figure 1B). Presence of a MUD also predicted for a lower cumulative incidence of relapse when compared to MRD or MMUD at 1-year post HSCT (6.8% vs 40% vs 25% respectively; p=0.049) (Figure 1C). GVHD prophylactic regimens containing Alemtuzumab or ATG-PTCy showed a trend towards improved RFS and OS when compared to other GVHD prophylactic regimens (median RFS 17.4 vs 10 months; p=0.19). Cytogenetic risk stratification, donor age, and CMML prognostic scores (Mayo/MDACC/CPSS) were not predictive of survival. Conclusions - Allogeneic hematopoietic stem cell transplantation remains the only curative modality for patients with CMML. Use of matched unrelated donors may improve outcomes after allogeneic HSCT in patients with CMML, primarily by reducing the cumulative incidence of relapse. Younger donor age and increased use of in vivo T cell depletion in unrelated donor transplants may have contributed to the improvement in outcome. Disclosures Lipton: Ariad: Consultancy, Research Funding; Bristol-Myers Squibb: Honoraria; Takeda: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding. Mattsson:Gilead: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees; ITB: Honoraria; Mallinkrodt: Honoraria; Jazz Pharmaceuticals: Honoraria.

Background Chronic graft-versus-host-disease (cGVHD) is one of the main causes of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HCT). Tyrosine kinase inhibitor such as Ruxolitinib, Ibrutinib and Imatinib showed a promising efficacy in cGVHD treatment. Ruxolitinib is a JAK-STAT inhibitor, reducing inflammation and immune pathway. Ibrutinib is a BTK inhibitor, blocking B cell-activating factor (BAFF), while Imatinib inhibits the platelet-derived growth factor receptor pathway activated by cGvHD-induced antibodies. The present retrospective study evaluated the efficacy of 3 TKIs for cGVHD at a single-centre in terms of 1) overall response rate (ORR), 2) clinical benefit (CB), 3) dose reduction of steroid, 4) failure-free survival (FFS) and 5) overall survival (OS). Patients and Methods A total of 43 patients who developed cGVHD after HCT and treated with TKI therapy for cGVHD at Princess Margaret Cancer Centre, Canada from August 2014 to April 2020 were evaluated in this retrospective study. 16 patients were treated with more than one TKI drug. A total of 62 lines of TKI therapy was evaluated, including Ruxolinitib (n=18), Ibrutinib (n=13) and Imatinib (n=31). The ORRs and CBs were assessed at months 3, 6 and 12, retrospectively. Responses were evaluated according to NIH scoring/staging/response assessment as part of standard clinical practice. CB was assessed considering clinical response as well as steroid dose reduction. For systemic steroid dose reduction, prednisone dose per kg per day was captured prior to Ruxolitinib start, at months 3, 6 and 12. Treatment failure was defined as 1) resistance requiring treatment switch, 2) non-relapse mortality (NRM), 3) relapse, 4) intolerance requiring treatment discontinuation. FFS and OS were calculated from the day of starting TKI therapy for cGVHD treatment. Results The patients and disease characteristics are summarized as follow: median age was 54 years (range 16 -70); 33 patients (53%) presented with classical cGVHD, while 29 patients (47%) with overlap syndrome; 14 (23%) presented with moderate and 48 (77%) with severe grade cGVHD. There was no difference in cGVHD subtype among 3 TKI subgroups (p= 0.478). The median number of organ involvement was 3 (range 1-5), and number of previous lines of therapy was 5 (range 3-9), implying that most of the patients were heavily pretreated for cGVHD. The mean (±S.E.) dosage of TKI treatment was as follows: Ruxolitinib was started at 15±1.1mg as initial dose and 20±0.7, 19±1.5, 22±4.4 mg per day in two divided doses on months 3, 6 and 12, respectively. Ibrutinib dose was 226±37, 256±37, 308±40 and 370±33 mg per day, while Imatinib dose was 106±6, 189±18, 196±16 and 190±19 mg per day prior to TKI starts, at months 3, 6 and 12, respectively. With a median follow up duration of 12 months, 19 (31%), 20 (32%), and 17 patients (27%) responded to TKI therapy at 3, 6, and 12 months without any difference of ORR among the TKIs (p=0.126, 0.554, 0.721 at 3/6/12 months; Figure A). The CBs were achieved in 47 (76%), 34 (55%), and 23 patients (37%) at 3, 6 and 12 months without any difference of CBs among the TKIs (p=0.187, 0.499, 0.750 at 3/6/12 months; Figure B). Prednisone dose (mg/kg/day) was 0.238±0.03 prior to TKI initiation, 0.177±0.03, 0.173 ± 0.03 and 0.110 ± 0.02 at 3, 6, and 12 months, respectively. No difference was noted in steroid dose among the 3 TKIs at each time point. However, the Ibrutinib group tends to require higher prednisone dose over time than other 2 groups. The FFS at 12 months was higher in Imatinib (71%) or Ruxolitinib groups (67%) than Ibrutinib group (46%; Figure C). The OS rate at 12 months was similar: 100 % in Ruxolitinib and Ibrutinib, and 96% in Imatinib group (Figure D). With regard to those patients treated with TKI for sclerotic GVHD (n= 39), the ORR were 11 (28%), 15 (38%) and 13 (33%) for 3, 6 and 12 months, while CB was noted in 32 (82%), 25 (64%) and 16 patients (41%) at 3, 6 and 12 months respectively. Of interest, Ruxolitinib was as effective as Imatinib in improving PROM score of sclerotic GVHD, while no significant improvement of PROM score was observed in the patients treated with Ibrutinib. Conclusion This retrospective study evaluated the efficacy of TKI drugs for cGVHD treatment in heavily pretreated patients. Ruxolitinib seems as effective as Imatinib to treat sclerotic GVHD. No difference was observed in OS at 12 months; while FFS appears better with Ruxolitinib and Imatinib over Ibrutinib. Figure Disclosures Lipton: Ariad: Consultancy, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria; Novartis: Consultancy, Research Funding; BMS: Consultancy, Research Funding.

There is paucity of data on pulmonary and ENT involvement in ANCA associatd vasculitis from India. We aimed to review the pattern of lung and upper respiratory tract involvement in patients with AAV diagnosed at our centre.A retrospective review of all AAV patients between January 2007 and June 2014 was done. A complete clinical evaluation for Pulmonary and ENT involvement was done. Advanced investigations including computed tomography (CT) bronchoscopy and nasal endoscopy were done when indicated. Proportion of involvement was noted and different variables among patient groups were compared.92 patients (median age 42 years; 60% female) of AAV were included. Clinical and/or radiological evidence of lung involvement was seen in 70 (76.1%) patients. Diffuse alveolar haemorrhage was present in 6 (60%) patients with MPA and 7 (10.1%) patients with GPA (p=0.002). ENT involvement was present in 55 (59.8%) patients and was more in GPA (p=0.000). Absence of renal involvement [p=0.047] and absence of GI involvement [p=0.012] were associated with ENT involvement in GPA.Pulmonary involvement was common in GPA, MPA and CSS, ENT involvement was almost characteristic of GPA. DAH was common in MPA. Population based and multicentre studies are needed to assess the true burden of organ involvement in AAV in the Indian population.

Recent studies in iron-depleted women have challenged the current approach of treating iron-deficiency anemia (IDA) with oral iron in divided daily doses. Alternate day dosing leads to more fractional absorption of iron. In this randomized controlled trial, we looked at the efficacy and safety of alternate-day (AD) versus twice-daily (BD) oral iron in all severity of IDA. Total of 62 patients were randomized, 31 patients in BD arm received 60 mg elemental iron twice daily while 31 patients in AD arm received 120 mg iron on alternate days. The primary endpoint of 2 g/dl rise in hemoglobin was met in significantly more patients in the BD arm at 3 weeks (32.3% vs. 6.5%, p0.0001) and 6 weeks (58% vs. 35.5%, p = 0.001). There was a significant rise in the median hemoglobin at 3 (1.6 vs. 1.1, p = 0.02) and 6 weeks (2.9 vs. 2.0 g/dl, p = 0.03) in the BD arm. However, the median hemoglobin rise in the AD arm at 6 weeks was not significantly different than the BD arm at 3 weeks. Alternate-day dosing for 6 weeks and twice-daily dosing for 3 weeks resulted in the provision of the same total amount of iron. There were more reports of nausea in the BD arm (p = 0.03). In conclusion, the choice of twice-daily or alternate-day oral iron therapy should depend on the severity of anemia, the rapidity of response desired, and patient preference to either regimen due to adverse events. Trial Registration: CTRI reg. no. CTRI/2018/07/015106 http://ctri.nic.in/Clinicaltrials/login.php.

Autologous hematopoietic cell transplantation (auto-HCT) using melphalan is the standard of care in the management of myeloma. Auto-HCT is a safe procedure with tolerable toxicity except in Asian-Indians. We hypothesized either one or a combination of factors: (1) frailty (assessed by IMWG frailty score), (2) generic melphalan pharmacokinetic area under the curve (AUC) assessed by high-performance liquid chromatography, and (3) pharmacogenetics of glutathione S-transferase (GSTP1) assessed by Sanger sequencing, to be associated with toxicity and survival outcomes post auto-HCT. Disease response was evaluated by IMWG response criteria at day +100 post auto-HCT. Gastrointestinal (GI) toxicity, infections, hospital stay, progression-free survival (PFS) were also recorded. A total of 35 patients were evaluated over 2 years (2016–2018). Frailty, not HCT-comorbidity index correlated with GI toxicity and infections. Overall there was an 11-fold variation in melphalan AUC with a median of 27.88 mg h/L (10.06–110.26). Patients with AUC more than the median had more GI toxicity and infections. Patients with wild-type GSTP1 polymorphism had more GI toxicity and infections. Frailty, AUC, or GSTP1 polymorphism did not impact hospitalization duration or PFS. A combination of the factors frailty, melphalan pharmacokinetics, and pharmacogenetics impacts GI toxicity and infections after auto-HCT in myeloma.

A 30-year-old man presented with fever, hepatosplenomegaly, and a rash over his lower limbs (palpable purpura). Evaluation revealed pancytopenia and hypergammaglobulinemia. A subsequent bone marrow examination and serology confirmed visceral leishmaniasis (kala-azar), while the biopsy of skin lesion suggested leukocytoclastic vasculitis. No alternate cause of vasculitis was forthcoming, and the patient was treated with conventional amphotericin B for 14 days after which resolution of symptoms (including the rash) was noted. Cutaneous vasculitis is an extremely rare complication following visceral leishmaniasis with no known cases reported thus far. Hence, a high index of suspicion is warranted in achieving timely diagnosis and initiation of appropriate therapy.

Background - Thrombocytopenia and poor graft function(PGF) after allogeneic hematopoietic cell transplantation (HCT) may be defined as incomplete count recovery or late cytopenias not due to relapse. There is lack of evidence based treatment for PGF with commonly used modalities being supportive care, second transplants and CD34+ selected stem cell boosts. Eltrombopag, a thrombopoietin receptor agonist, stimulates proliferation and differentiation of hematopoietic stem cells (HSC). It has shown efficacy for PGF in observational studies, but is not approved for this indication. Cost of this drug is a major concern in state sponsored health care systems. Methods - We retrospectively and prospectively collected data about patients who received Eltrombopag for thrombocytopenia and poor graft function after HCT. Post HCT thrombocytopenia was defined as persistent platelet count ≤ 20 x 10^9/l or transfusion dependence. PGF was defined if there was persistence of 2/3 cytopenias: thrombocytopenia, neutropenia (≤ 1.5 x 10^9/l) and/or haemoglobin ≤ 70g/l or transfusion dependence after day 28 of HSCT with complete donor chimerism and no evidence of relapse. Transplant characteristics, post-transplant complications and transfusion history was noted. In treated patients, Eltrombopag was initiated at 50 or 100mg daily and increased every 2 weeks to maximum of 150mg daily based on response. Response criteria: Complete Response (CR) - sustained platelet count ≥ 50 x 10^9/l, haemoglobin≥ 100g/L and ANC ≥ 1.5x10^9/L without transfusions; Partial response (PR) - platelet count 20-50 x 10^9/l or Hb 7-10g/L or ANC 0.5-1.5 x 10^9/l. Cost of transfusions were calculated from estimates of Canadian Blood Services and of hospital admissions were based on local hospital estimates. Cost estimation prior to Eltrombopag was calculated by the cost of supportive care from diagnosis of PGF or thrombocytopenia to initiation of Eltrombopag. Cost estimation post Eltrombopag was done by calculating the cost of drug intake + cost of supportive care (if any) after initiation of Eltrombopag. Primary outcomes were efficacy of drug and transfusion free survival; secondary outcomes were cost comparison between estimated cost prior to Eltrombopag and estimated cost after initiation of Eltrombopag. Results: 15 patients (males 66.67% (n=10); median age - 59 years) received Eltrombopag (Table 1). Indication of Eltrombopag was PGF in 86.7% (n=13) and isolated thrombocytopenia in 13.3% (n=2) patients. Response and cost analysis were limited to the 13 patients with at least 8 weeks follow-up after initiating Eltrombopag. After 8 weeks of Eltrombopag, Overall Response rate(ORR) was 76.9% (n=10; CR = 7; PR = 3). With median follow up of 6.2 months the drug was tapered or discontinued in 60% (n=6) patients showing response. All responders became transfusion independent within 8 weeks of maximum dose of Eltrombopag. The 3-month transfusion free survival after Eltrombopag was 70.7% (Figure 1A). Two out of three patients who did not respond to Eltrombopag died during the study period. The estimated median OS of non-responders vs responders = 12.4 months vs NR; p-0.063; Figure 1B). Eltrombopag was well tolerated with no incidence of serious adverse effects (Liver enzyme elevation, GI toxicity) to report. Rough estimates of cost analysis were done in patients who had response to Eltrombopag. These patients required median (IQR) of 15 (2-25) PRBC transfusions and 46 (32-96) pooled platelet transfusions with median 20 days of hospitalization due to cytopenia complications prior to 4 weeks after starting Eltrombopag. The median (IQR) duration of Eltrombopag exposure was 9.8 (6.3-25.6) weeks. The cost of supportive care before Eltrombopag was marginally higher than calculated total cost of Eltrombopag and subsequent supportive care treatment (Median cost 35311$ vs 33751 $CAD; p=0.9) (Figure 1C). The crude cost estimate of supportive care did not include cost estimates of human resources (including nursing), hospital visit time, time off work, and quality of life. Conclusion - Eltrombopag is a safe and efficacious therapy for thrombocytopenia and poor graft function after allogeneic HCT with response in 77% of patients. Preliminary cost analysis shows that Eltrombopag is cost neutral by reducing supportive care and hospitalization costs and may be especially relevant in countries where supply of safe and adequate blood products is a challenge. Figure Disclosures Lipton: Ariad: Consultancy, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria; Novartis: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding. Mattsson:ITB: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees; Mallinkrodt: Honoraria; Jazz Pharmaceuticals: Honoraria; Gilead: Honoraria. OffLabel Disclosure: Eltrombopag is approved for ITP and Aplastic Anemia. It is currently not approved for thrombocyotpenia and poor graft function after Allogeneic Hematopoietic Cell Transplantation in Canada.

Consolidations in the pulmonary parenchyma are mostly infective, although they can rarely be due to autoimmune and neoplastic processes. Consolidations, especially in the setting of underlying immunosuppressive haematological malignancy, are usually presumed infective by the treating physician. Pulmonary involvement in chronic lymphocytic leukaemia presenting as consolidations and type 1 respiratory failure, responding to systemic chemotherapy, is a rare and uncommon presentation.

Background Therapy related acute myeloid leukemia (t-AML) constitutes a subset of AML that has an increased proportion of high risk cytogenetic and molecular features, poor response to therapy, higher relapse, and decreased overall survival. The incidence ranges from 10-20% across various studies. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) offers a potential cure in t-AML, with disease free survival reported up to 30% at 2 years. Most studies on HSCT in t-AML have limited number of patients and are confounded by the inclusion of patients with secondary AML and therapy related myelodysplastic syndromes (t-MDS). We aim to report our 20-year experience of allo-HSCT in t-AML and identify predictors of survival. Patients and Methods We retrospectively reviewed all cases of t-AML who underwent allo-HSCT at our centre from June 1999 to July 2019. We collected data for demographic characteristics, prior malignancy and treatment, latent period before AML, cytogenetic and molecular characteristics of AML, induction treatment received, transplant details (donor details, conditioning regimens, GVHD prophylaxis) as well as post-transplant complications (transplant related mortality, occurrence and severity of acute and chronic GVHD, CMV and EBV reactivations). Primary outcome evaluated was overall survival and secondary outcomes were relapse rate and relapse free survival (RFS). Cox-proportional hazards regression model was used to identify predictors of survival. Results Fifty-two patients underwent allo-HSCT for t-AML during the study period. 58% were male (n=30). Median age at HSCT was 55.5 years (Range 18-70). Baseline characteristics are summarized in Table 1. Complex cytogenetics were present in 23.2% (n=12) patients, while 11q23 rearrangement (MLL-KMT2A), monosomy 7, monosomy 5, and 17p deletion were present in 15.4% (n = 8), 15.4% (n= 8), 7.7% (n = 4) and 7.7% (n=4) patients respectively. Based on the ELN 2017 risk stratification schema, 13.5% (n=7) patients could be considered favorable risk based on cytogenetic and molecular profiles, 36.5% (n=19) intermediate risk, and 57.7% (n=30) in poor risk category. Performance status prior to transplant was ECOG 0/1 in 71.2% (n=37) patients, and 2 in 28.8% (n=15) patients. Myeloablative conditioning was used in 30.8% (n=16) patients, and reduced intensity conditioning in 69.2% (n=36). GVHD prophylaxis was CyclosporineA(CSA)/Methotrexate in 23.1% (n=12), Alemtuzumab/CSA in 21.2% (n=11), ATG/CSA/PTCy in 28.8% (n=15), and other regimens in 26.9% (n=14) patients. Transplant related mortality (death before day+100) was 21.1% (n=11). Acute and chronic GVHD (any grade) occurred in 61.5% (n = 32) and 28.8% (n=15) patients respectively. Eleven patients (21.2%) relapsed with a median RFS of 8 months (Range 0.17-158). Median OS of the whole cohort was 8.9 months (0.17-158 months). No patient had a relapse of their primary malignancy during follow up. RFS at 12 and 24 months were 46% and 28% while OS at 1 and 2 years was 46% and 30%, respectively. Significant predictors of reduced OS (Figure 1a,b,c) after day+100 of HSCT by Cox-regression were ECOG performance status 2 (Hazard ratio - 6.1; p value 0.003), GVHD prophylaxis with CSA/methotrexate (HR - 4.5; p value 0.01), and haploidentical donor transplantation (HR - 34; p value - 0.002). Cytogenetics were a predictor of OS in univariate analysis but not in multivariate regression analysis. No difference in OS was found between patients who underwent HSCT 2010 or prior versus after 2010. Conclusions Patients with favorable cytogenetic profile, better performance status, and an HLA matched donor may have better outcomes after allo-HSCT in therapy related AML. Patients with unfavorable cytogenetic risk profiles may require more intense therapy or post-transplant maintenance therapy to prevent relapse. Disclosures Michelis: CSL Behring: Other: Financial Support. Mattsson:Gilead: Honoraria; Celgene: Honoraria; Therakos: Honoraria.

Introduction Therapy related acute leukemias are late complications of treatment with mutagenic agents for both malignant and non-malignant disorders. The prevalence of therapy induced Acute lymphoblastic leukemia(t-ALL) is thought to be much less than that of t-AML/MDS, with our institute reporting a 6.9% prevalence of t-ALL among all patients of adult ALL. There is limited data on role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in t-ALL. Recent reports suggested comparable outcomes with de-novo ALL after allo-HSCT. We aim to report our 20-year experience of allo-HSCT in t-ALL. Patients and Methods We retrospectively reviewed all cases of t-ALL who underwent allo-HSCT at our centre from October 1998 to July 2019. Patients were analysed and compared for demographic features, prior malignancy and its treatment, latent period before ALL, clinical, cytogenetic and molecular characteristics of ALL, induction and consolidation treatment received, transplant details including donor details, conditioning regimens, GVHD prophylaxis as well as post-transplant complications (including transplant related mortality, occurrence and severity of acute and chronic GVHD, CMV and EBV reactivations), relapse rate, relapse free survival (RFS) and overall survival (OS). Predictors of survival were calculated by Cox-Regression Analysis. Results A total of 18 patients underwent allo-HSCT for t-ALL. M:F ratio was 1:1. Median age at allo-HSCT was 44 years (range 20-70 years). Baseline characteristics, prior malignancy and treatment received are summarized in Table 1. Median latent period from prior malignancy to diagnosis of ALL was 44.8 months (range 6-157 months). Complex cytogenetics was present in 16.7% patients (n=3) while 11q23 rearrangement (KMT2A-MLL) and t(9;22) rearrangement was seen in 33.3% (n=6) and 22.2% (n=4) patients respectively. Median time to allo-HSCT from diagnosis of t-ALL was 5 months. Stem cell donors were matched related, matched unrelated and haplo-identical in 27.8% (n=5), 55.6% (n=10), and 16.7% (n=3) patients, respectively. Conditioning regimen was myeloablative in 44.4% (n=8) patients and reduced intensity in 55.6% (n=10) patients. GVHD Prophylaxis used was ATG-CSA-PTCy in 50% (n=9) patients, CSA/MMF in 22.2% (n=4) patients, and other regimens in 27.8% (n=5) patients. Post HSCT CMV and EBV virus reactivation occurred in- 33.3% (n=6) and 47.1% (n=8) patients, respectively. Acute GVHD (any grade) occurred in 70.6% (n = 12) while chronic GVHD (any grade) occurred in 31.3% (n=5) patients. Transplant related mortality (Death before day 100) occurred in 27.8% (n=5) patients. Four (22.2%) patients relapsed. Median RFS was 4 months (Range 0.5-194 months) while median OS was 5.88 months (Range 0.5-194 months) (Figure 1a&b). One patient (5.5%) had relapse of their primary malignancy (CA Breast) 12 years after allo-HSCT. One year RFS and OS for all patients (excluding patients who have not completed one year of followup after HSCT but have not relapsed or died) was 43.8% and 46.7% respectively. None of the basic disease characteristics, treatment characteristics, or transplant or post-transplant parameters including donor type, conditioning received, GVHD prophylaxis used, occurrence of Acute or chronic GVHD etc. were significantly predictive of OS and RFS on Cox-Regression analysis, though the analysis is limited by the small sample size. Conclusions Therapy related ALL is an uncommon but increasingly recognized disease entity. Our outcomes of Allogeneic HSCT in t-ALL were comparable to that in de novo ALL as per previously reported literature. Multicenter studies on t-ALL with more patients and longer follow up duration may provide us with predictive factors of relapse and survival post allogeneic HSCT. Disclosures Michelis: CSL Behring: Other: Financial Support. Mattsson:Celgene: Honoraria; Therakos: Honoraria; Gilead: Honoraria.

Background Multiple myeloma (MM) is a hematologic malignancy of plasma cell origin. MM primarily affects bone marrow, but extramedullary sites can also be involved. Myelomatous pleural effusion (MPE) is an atypical and rare complication of MM. We aimed to systematically study the incidence and clinicopathologic profile of patients with MPE in a real-world setting. Patients and Methods In this retrospective study, 415 consecutive patients with MM managed at a tertiary care center in North India during a study period of January 1, 2010 to December 31, 2015 were evaluated for MPE. The patients with MPE were analyzed for their clinical profile, diagnosis, treatment, and outcomes. Results Of these 415 patients, 11 (2.65%) patients had MPE. The median age of the study population was 50 years with male preponderance. The majority of these patients had immunoglobin (Ig)G Kappa disease. All patients had higher than International Staging System stage I disease. MPE was a presenting feature at MM diagnosis in 45.45% (n = 5) of the patients, whereas the rest developed MPE during follow-up. MPE presented predominantly (81.8%) as a unilateral effusion. Concurrent extramedullary involvement at other site was seen in 45.45% (n = 5), with 3 (27%) patients having concurrent myelomatous ascites. Six of these were managed aggressively, whereas 5 patients opted for palliation. The outcomes were dismal (90.9% mortality), with a median survival of 2.47 months. Conclusion MPE is a rare entity, and positive outcomes of therapy remain low with dismal prognosis.

The electrocardiogram (ECG) is a simple, universally available tool in emergency departments used in evaluation of acute chest pain. Among the differential diagnosis, Acute Pulmonary Thromboembolism (PTE) is important to recognize as the diagnosis, carries serious therapeutic and prognostic implications. A 28-year-old male presented to the emergency department with acute onset shortness of breath and chest pain for two days and two episodes of haemoptysis. He had sustained a road traffic accident with fracture of both bones of right leg one month back for which he had undergone open reduction and internal fixation. On examination, he was tachycardic (pulse rate-152/min) and tachypnoeic (respiratory rate-26/min) with normal blood pressure (116/78 mm of Hg) and oxygen saturation (96%) on breathing ambient air. His right lower limb was warm and swollen with tenderness along the femoral vein. The electrocardiogram (ECG) showed sinus tachycardia, right ventricular strain, right bundle branch block pattern and S1Q3T3 pattern [Table/Fig-1] suggestive of PTE. Compression ultrasound scan of right lower limb revealed echogenic contents in right femoro-popliteal veins indicative of Deep Vein Thrombosis (DVT). Computed tomographic angiogram of pulmonary arteries showed hypodense filling defect suggestive of thrombus involving the right main pulmonary artery [Table/Fig-2], extending into its descending branch. A 2-dimensional echocardiogram showed mild tricuspid regurgitation and mild right ventricular dilatation. Since the patient was haemodynamically stable, thrombolysis was not attempted. He was started on subcutaneous enoxaparin at 1 mg/kg/dose twice daily along with oral anticoagulation with warfarin. Patient improved and was discharged. On follow-up at one month, patient is asymptomatic for DVT or PTE and INR is in therapeutic range. [Table/Fig-1]: A 12-lead electrocardiogram (ECG) showing sinus tachycardia (heart rate- 150/min), right bundle branch block pattern (black arrows), T-inversion in aVF and typical S1Q3T3 pattern (red arrows) suggestive of pulmonary thromboembolism. [Table/Fig-2]: Axial computed tomographic angiogram section of pulmonary arteries showing hypodense filling defect (arrowhead) suggestive of thrombus involving the right main pulmonary artery. Common ECG abnormalities in PTE include sinus tachycardia and T wave inversions in precordial leads and a ventricular fibrillation (VF), right bundle branch block pattern, S1Q3T3 pattern, QR pattern in V1, QS pattern in precordial leads, ST-elevation in precordial leads and low voltage in limb leads. Classic changes like S1Q3T3 pattern tend to occur with more severe forms of PTE and correlate well with mortality [1]. S1Q3T3 pattern is a marker of acute cor-pulmonale and can occur with conditions like severe bronchospasm and pneumothorax [2]. Composite scores based on ECG in PTE can help in patient management. Using a 21-point scale, a score ≤3 in predicted normal right ventricular function [3]. QR in V1, ST-depression in V4-V6 and ST-elevation in lead III and V1 are associated with in-hospital mortality [1]. This case illustrates the classical ECG findings of PTE and the importance of an easily available, simple diagnostic test in diagnosing a life threatening condition. The classical signs in ECG can be used as a decision tool for further imaging and can also be used as an indicator for early referral of a patient especially in resource poor settings. To conclude, ECG in PTE can show a spectrum of changes from being normal to having multiple suggestive abnormalities. The ECG changes in PTE are not specific and similar changes may result from wide array of causes conferring to the principle of Hickam’s dictum. In general, the number of abnormalities on ECG correlates well with pulmonary artery pressures and the severity of PTE. Even though ECG can give a clue to the diagnosis of PTE, its actual role lies in prognostic assessment and hence can be used as a decision tool for further imaging and investigations especially in resource poor settings.

A 15-year-old boy with night blindness since the age of six presented to the outpatient wing with a history of growth retardation, poor scholastic performance and failure to attain secondary sexual characters. Retinal imaging showed the presence of pigmentary retinal degeneration and attenuated vessels suggesting retinitis pigmentosa [Table/Fig-1]. Physical examination revealed dysmorphic facies [Table/Fig-2] - widened intercanthal distance, low set ears, depressed nasal bridge and a flattened occiput [Table/Fig-3]. Also truncal obesity [Table/Fig-3], shortened metacarpals/phalanges [Table/Fig-4], polydactyly [Table/Fig-5], and underdeveloped testes were noted. In view of the constellation of findings, a diagnosis of Bardet–Biedl Syndrome (BBS) was made. Nutritional supplementation was advised and the patient was referred for IQ assessment and genetic counseling. [Table/Fig-1]: Fundus photograph of the left eye demonstrating pigmentary changes and arteriolar attenuation characteristic of retinitis pigmentosa. [Table/Fig-2]: Dysmorphic face with depressed nasal bridge, widened intercanthal distance and low set ears. [Table/Fig-3]: Depicting the flattened occiput and trucal obesity. [Table/Fig-4]: Brachydactyly, shortened metacarpals and phalanges. [Table/Fig-5]: Postaxial polydactyly. In 1866, Laurence and Moon described four patients with retinal degeneration, obesity, and cognitive deficit [1]. Bardet and Biedl separately reported similarly affected individuals who also had postaxial polydactyly and the condition was coined Laurence– Moon–Bardet–Biedl syndrome [2,3]. The syndrome is often divided into two entities: Laurence–Moon syndrome and Bardet–Biedl Syndrome (BBS), but since there is considerable overlap, BBS is now the globally accepted name. Beales et al., proposed a modified criteria in 1999, requiring four primary features or three primary features with two secondary features for the diagnosis [4]. Rod-cone dystrophy, polydactyly, truncal obesity, genital anomalies, chronic kidney disease and learning disabilities form the primary features, while speech delay, developmental delay, diabetes, dental anomalies, congenital heart disease, brachydactyly/syndactyly, ataxia/poor coordination and anosmia/hyposmia are the secondary features. The diagnosis of BBS is delayed and considered only when the child develops visual problems associated with rod-cone dystrophy [5]. Postaxial polydactyly may be the only hint to the diagnosis at birth and hence its presence should alert physicians to look for other features of BBS [5]. Our patient had five primary and three secondary features. BBS is a rare and complex syndrome, autosomal recessively inherited, involving mutations of proteins that form components of the ciliary apparatus. But as emphasized by our patient, the diagnosis remains clinical. Treatment and rehabilitation involve a multidisciplinary approach. Early recognition and treatment of co-morbidities are imperative to improve the quality of life.

Infectious aetiologies are the most common causes of primary adrenal failure (Addison’s disease) in low/middle-income countries while in the western world autoimmune causes predominate. The infections attributed to cause Addison’s include disseminated gonococcal infection, tuberculosis, histoplasmosis, cryptococcosis and cytomegalovirus (CMV) infection. Here, we describe two classical cases of Addison’s due to infections of the adrenal gland. ### Case 1 A 55-year-old woman from North India was admitted with history of multiple episodes of vomiting. She had history of severe loss of appetite and loss of weight. There was also history of increased body pigmentation for the last 6 months. At admission, she was drowsy with tachycardia of 116 beats per minute and her blood pressure was 80/50 mm Hg in supine position associated with a significant postural drop. There was hyperpigmentation of fingers, face, oral mucosa and flexures. The rest of the system examination did not reveal any significant clinical finding. Initial biochemical parameters showed serum sodium of 116 meq/L and serum potassium of 6.1meq/L. Arterial blood gas analysis showed pH 7.2 and bicarbonate 14.9 mEq/L. A diagnosis of acute adrenal insufficiency was made, and after drawing blood sample for cortisol and adrenocorticotrpic hormone (ACTH), she was given a 100 mg bolus dose of intravenous hydrocortisone and 2 L of 0.9% saline. Investigations showed serum cortisol of 39.02 nmol/L (171–536) and elevated ACTH of 818.8 pg/mL (5–60) confirming diagnosis of primary adrenal insufficiency. With initial management, her blood pressure improved and steroids were tapered to oral hydrocortisone (25 mg/day) with oral fludrocortisone 0.1 mg once a day. Contrast-enhanced CT (CECT) of the abdomen revealed bilateral symmetrical enlarged adrenals with preservation of contour without any calcifications (figure 1A). The rest of her hormone profiles were within normal limits ruling out a polyendocrinopathy syndrome. Antinuclear antibody immunofluorescence (ANA-IF) and retroviral serology were negative. CT-guided biopsy from enlarged adrenal glands was performed which revealed dense lymphoplasmacytic cell infiltrates with collection of epithelioid cells …

A 19-year-old woman presented with a history of severe lower backache and asymmetric proximal lower limb weakness during the past 3 months. In addition, she also suffered from lower motor neuron-type bladder and bowel symptoms. On examination, paraparesis was noted. Further, sensory examination suggested patchy asymmetric sensory loss in both lower limbs with saddle anaesthesia and areflexia. A clinical diagnosis of Conus-Cauda syndrome was made and contrast-enhanced MRI of the lumbar and sacral spine was done, which confirmed the presence of a mass lesion within the spinal canal involving the cauda equina extending up to the sacral level. She underwent partial resection of the lesion following which the neurological deficits and lower backache resolved. Histopathological evaluation and immunohistochemical analyses uncovered Rosai-Dorfman disease. There was no evidence of disease elsewhere in the body. Since the patient improved significantly following surgery and exhibited no further neurological worsening, she remains under close follow-up.