FLAG based v/s Standard 3 + 7 induction therapy in treatment naïve Acute Myeloid Leukemia: Time to think "beyond anthracyclines".

Daunorubicin and Cytarabine (DA; 3 + 7) has been the standard frontline Acute Myeloid Leukemia (AML) induction regimen resulting in Complete Remission (CR) rates of 50-70%. It is associated with induction mortality of 15-30%. We report a comparative analysis of DA versus fludarabine, cytarabine, G-CSF (FLAG) + /- Venetoclax in resource constrained settings. We conducted a single center, retrospective analysis of 37 treatment naïve fit AML patients from May 2021 to December 2022 who received either standard DA regimen (Group 1) or FLAG + /- Venetoclax (Group 2). The median patient age was 36.6 years in DA arm (n = 18) as compared to 40.1 years in FLAG arm (n = 19). CR rates at day 28 were 55.5% in group 1 and 89.4% in group 2 (odds ratio [OR], 7.20; 95% confidence interval [CI], 1.274 -40.678; P = 0.012). Patients in FLAG based therapy arm had shorter duration of neutropenia (P = 0.003), fewer episodes of grade 3 febrile neutropenia (P = 0.0228), shorter duration of antibiotic therapy (P = 0.03), lesser need of 3rd line antibiotic therapy (P = 0.0228). Mortality rates were 16.6% (n = 3) in (group 1) and 0% (n = 0) in (group 2) (p = 0.105). Our analysis supports that FLAG based induction regimen is an effective and well-tolerated therapy in treatment naïve fit AML patients.

High Risk Acute Promyelocytic Leukemia - An Enigma for Hematologists: Optimizing Treatment with APML-4 Protocol.

Management of Acute Promyelocytic Leukemia (APML) has improved drastically after the introduction of ATRA (All-trans-retinoic acid) and Arsenic trioxide (ATO). The use of APML-4 protocol has shown its effectiveness in Australian population. We know that high-risk APML represents a subset with poor outcomes. There is scarcity of literature reporting outcomes of high-risk APML from India. We present a 5-year retrospective analysis of the safety and efficacy of APML-4 protocol in our 28 high-risk patients. Of 28 patients, there were 8(28.5%) early deaths; all 20 patients (100%) who were alive achieved hematologic complete remission post-induction and molecular complete remission post-consolidation. The 5-year disease free survival, failure free survival (FFS) and overall survival were 100%, 69% and 69% respectively. Factors affecting FFS were age > 45 years (p = 0.008), baseline ECOG-PS > 1 (p < 0.0001), and grade 3-4 differentiation syndrome (p = 0.008). APML-4 protocol in high-risk patients is capable of achieving excellent disease control with less toxicities. While early induction deaths in high-risk APML still remain an issue, protocol modifications (for steroid and anthracyclines) are important considering high frequency of infections at baseline and during induction therapy in our population.

Study of clinical characteristics, risk factors and outcomes for tuberculosis post allogeneic stem cell transplant: never count it out.

BACKGROUND: Allogeneic stem cell transplant (AlloSCT) recipients remain at a higher risk of developing tuberculosis (TB), especially in endemic populations. We conducted a retrospective study to identify the incidence, clinical presentation, and risk factors for active TB among our alloSCT recipients. METHODS: Records of all patients transplanted between 1 January 2012 and 31 July 2020 were reviewed. Patients were followed up for outcome until 30 September 2020. None of the patients received prophylactic anti-tubercular drugs. Proven diagnosis of active TB was considered if Mycobacterium tuberculosis (MTB) was cultured from clinical samples or acid-fast bacilli (AFB) or MTB demonstrated on Ziehl-Neelsen (ZN) staining or histopathology or XPERT MTB, while probable diagnosis of TB was considered if histopathology findings were suggestive of caseation necrosis/epithelioid cell granulomas without any evidence of malignancy or lymphocyte rich exudative effusions (pleural/pericardial) without an alternative cause. RESULTS: Among 381 alloSCT recipients, 15 patients (3.9%) developed TB at median of 246 (74-279) days post AlloSCT, after being symptomatic for a median of 22 (7-60) days, amounting to a cumulative incidence of 4.9%. All patients were started on four-drug anti tubercular therapy, ATT [Rifampicin, Isoniazid, Ethambutol, Pyrazinamide (RHEZ)], of which five patients developed hepatotoxicity at a median of 12 days after start of ATT, leading to drug modification. At last follow up, TB was cured in 13 (86.67%) patients, one succumbed to disease relapse, while others are still on treatment. Age ⩾ 30 years, immunosuppression for graft versus host disease (GvHD) > 6 months, prior use of tyrosine kinase inhibitors (TKI) and chronic GvHD on univariate analysis and immunosuppression for GvHD > 6 months on multivariate analysis were found to be associated with development of TB. CONCLUSION: A high index of suspicion with timely workup and treatment of TB is the key in AlloSCT recipients, especially in endemic TB populations.

HIV - Old Foe with a New Face.

We report a case of a middle aged seropositive male, virologically well suppressed on second line ART (Anti-Retroviral therapy) who presented with a subacute history of neurological symptoms. On imaging and CSF (cerebrospinal fluid) evaluation, he was found to have CD8 encephalitis - a new, rare but treatable entity. To the best of our knowledge, no case has been reported from India.

Double - Trouble- Relapsing Leishmaniasis in a Virologically Suppressed HIV Positive Patient.

We present a case of a middle aged male, with long standing retroviral disease on second line ART (Anti-Retroviral Therapy) with three episodes of visceral leishmaniasis diagnosed on bone marrow examination treated with a combination of liposomal amphotericin B and miltefosine.

Enoxaparin Induced Skin Lesions in Pregnancy: A Rare But Clinically Recognizable Association.

We report the case of a 29 year old pregnant female who experienced itching with erythematous plaques on prophylactic enoxaparin for recurrent fetal losses. These lesions generalized on rechallenge but erythema and itching gradually resolved after 4 weeks of discontinuation. Cutaneous adverse events with heparin have been reported (Villanueva et al. in Actas Dermosifiliogr 103:816-819, 2012; Neloska et al. in Acta Dermatovenerol Croat 23:223-224, 2015; Maldonado et al. in Clin Exp Dermatol 37:707-711, 2012; Schindewolf et al. in Lancet 380:1867-1879, 2012; Tassava and Warkentin in Am J Hematol 90:747-750, 2015), some specifically with enoxaparin (Villanueva et al. 2012; Neloska et al. 2015).

Bullous Pemphigoid as a Harbinger of Metastatic Cholangiocarcinoma - A Rarity.

Bullous pemphigoid (BP) is an autoimmune blistering disorder of the skin first described in 1953. A decade later, antibodies were described targeting the cutaneous basement membrane zone. The association of Bullous pemphigoid with malignancy is debatable1 but reported in many case reports.2-6 We report a 79 year old male with cholangiocarcinoma that presented with bullous pemphigoid as a paraneoplastic phenomenon.

Isolated palatal weakness without optic neuritis as the presenting manifestation of multiple sclerosis and its diagnostic dilemma with acute disseminated encephalomyelitis in a young boy.

We present a case of a young boy who at initial presentation was diagnosed as acute disseminated encephalomyelitis (ADEM) but subsequently on follow-up was diagnosed as multiple sclerosis (MS). Differentiating ADEM from MS in their first presentation can be tricky as the features may not be typical of anyone. The importance lies in the close follow-up of these patients.

Bilateral painful parotid lumps and a lump in the groin: An uncommon presentation of common Kikuchi's disease.

Kikuchi-Fujimoto disease (KFD) is an under-recognized disease most commonly presenting with cervical lymphadenopathy, fever, and cytopenias in young females. Bilateral parotid enlargement is usually caused by infections (e.g., mumps) and autoimmune conditions (e.g., Sjogren syndrome). Parotid enlargement, inguinal lymphadenopathy, and pyrexia of unknown origin are uncommon presenting features of KFD and should be suspected in the appropriate setting.

Refractory anemia in human immunodeficiency virus: Expect the unexpected.

Pure red cell aplasia (PRCA) is an uncommon hematological disorder affecting selectively the erythroid cell lines. PRCA is defined as anemia with normal leukocyte and platelet counts, a corrected reticulocyte count <1%, <5% erythroid precursors in the bone marrow and an absence of hemolysis. We describe a case of Zidovudine (AZT) induced PRCA causing severe anemia in a patient taking antiretroviral therapy (ART) after 4 months of starting therapy and in whom all other causes were excluded. The hematological abnormalities resolved after AZT was replaced with tenofovir and the patient remained transfusion independent thereafter. A slowly progressive normocytic-normochromic anemia and reticulocytopenia, without leukopenia and thrombocytopenia in a patient, should raise the suspicion of PRCA. Search for underlying diseases, infections and drugs may help in the diagnosis and etiology of acquired PRCA. Elimination of potentially causative factors may induce complete recovery. AZT is a well-known cause of anemia and thus should be used with caution in the initiation of ART.