Elevated monoclonal and polyclonal serum immunoglobulin free light chain as prognostic factors in B‐ and T‐cell non‐Hodgkin lymphoma

The serum immunoglobulin free light chain (FLC) assay quantitates free kappa (κ) and lambda (λ) light chains. FLC elevations in patients with diffuse large B‐cell lymphoma (DLBCL), Hodgkin lymphoma (HL), and chronic lymphocytic leukemia (CLL) are associated with an inferior survival. These increases in FLC can be monoclonal (as in myeloma) or polyclonal. The goal was to estimate the frequency of these elevations within distinct types of B‐cell and T‐cell non‐Hodgkin lymphoma (NHL) and whether the FLC measurements are associated with event‐free survival (EFS). We studied serum for FLC abnormalities using normal laboratory reference ranges to define an elevated κ or λ FLC. Elevations were further classified as polyclonal or monoclonal. Four hundred ninety‐two patients were studied: 453 B‐cell and 34 T‐cell NHL patients. Twenty‐nine % (142/453) of patients had an elevated FLC of which 10% were monoclonal elevations. Within B‐cell NHL, FLC abnormalities were most common in lymphoplasmacytic (79%), mantle cell (68%), and lymphomas of mucosa associated lymphoid tissue (31%); they were least common in follicular (15%). The hazard ratio (HR) for EFS in all patients was 1.41 (95% CI; 1.11–1.81); in all B‐cell NHL the HR was 1.44 (95% CI 1.11–1.96); in all T‐cell NHL the HR was 1.17 (95% CI 0.55–2.49). FLC abnormalities predicted an inferior OS (HR = 2.75, 95% CI: 1.93–3.90, P < 0.0001). The serum FLC assay is useful for prognosis in both B‐cell and T‐cell types of NHL. In B‐cell NHL further discrimination between a monoclonal and polyclonal elevation may be helpful and should be analyzed in prospective clinical trials. Am. J. Hematol. 89:1116–1120, 2014. © 2014 Wiley Periodicals, Inc.     

Efficacy of a new model for delivering integrated TB and HIV services for people living with HIV/AIDS in Delhi – case for a paradigm shift in national HIV/TB cross-referral strategy

Under National TB/HIV framework, all TB patients are referred by Revised National Tuberculosis Programme (RNTCP) service providers to Integrated Counseling and Testing Centers (ICTCs) for voluntary counseling and testing (C&T) and ICTC “TB-suspects” are referred to RNTCP facilities for TB diagnosis and treatment. HIV–TB coinfected patients are then referred to Anti Retroviral Treatment (ART) center for initiation of ART between two weeks and two months of initiating TB treatment. During the third phase of National AIDS Control Programme (NACP-III, April 2007–April 2012), 30749/130503 (23.6%) TB/HIV cross-referrals were lost to follow up (LTFU) and there was missed opportunity for 940/1884 (49.9%) HIV–TB coinfected patients for initiation of ART during TB treatment. This motivated Delhi State AIDS Control Society (DSACS) and State TB Cell (STC) to revise existing cross-referral strategy. The new strategy was launched in May 2012, wherein HIV–TB coinfected and HIV-positive “TB-suspects” were referred to nearest ART center for HIV care and investigations of TB at Chest Clinic/Designated Microscopy Centre (DMC) located within the same hospital instead of referral to area RNTCP facility. Outcome of the strategy was evaluated in March 2013. The new HIV–TB cross-referral strategy in Delhi has shown advantage over national strategy: first, improved retention of coinfected clients in HIV care; second, ensured timely initiation of TB-treatment and ART; and third, significantly improved survival of HIV–TB coinfected patients.     

MTHFR Gene Polymorphisms and the Risk of Acute Lymphoblastic Leukemia in Adults and Children: A Case Control Study in India

Genetic polymorphisms in the methylene tetrahydrofolate reductase (MTHFR) gene have been associated with the development of acute leukemias and various malignancies. The role of MTHFR polymorphism in the development of pediatric acute lymphoblastic leukemia (ALL) has been extensively studied among north Indians in various settings, yet its association with acute leukemias remains unresolved. To evaluate the relationship between functional MTHFR polymorphisms, C677T and A1298C and possible effect on risk of ALL in adults and children in North Indian population by comparing them with healthy controls. DNA was isolated from peripheral blood of 184 ALL patients (33 adults, 151 children) and 155 controls and analyzed by a PCR-restriction fragment length polymorphism assay. The frequency of MTHFR 677CT and 1298 AC genotypes were significantly lower among adult ALL cases when compared to the controls. We found a 1.74-fold reduced risk of ALL in individuals with 1298AC polymorphic variant and a 9.17-fold decreased risk of adult ALL. However, no statistically significant difference was evident between the above polymorphisms and susceptibility to ALL in children. Polymorphisms in the MTHFR gene possibly modulate risk of ALL in north Indian adults but not in children, although larger studies are needed.     

Successful Aortic Valve Replacement Surgery in a Patient with Severe Haemophilia a with Low Titre Inhibitor

Acute leukemia, secondary myelodysplasia and paroxysmal nocturnal hemoglobinuria evolving from severe aplastic anemia (AA) following immunosuppressive therapy are well recognized. However, severe AA occurring after complete remission of acute promyelocytic leukemia (APL) has been documented only once in 2009. We report a case of 30-year-old male diagnosed with APL who achieved complete cytogenetic remission with all-trans retinoic acid based induction regimen and developed severe AA few months later during maintenance therapy.     

Mortality in children with juvenile dermatomyositis: two decades of experience from a single tertiary care centre in North India

Survival and outcomes have improved considerably among patients with juvenile dermatomyositis (JDM) in the west. However, mortality continues to be high in the developing world. There is paucity of literature on this aspect of JDM from developing countries. We reviewed case files of all patients with JDM registered in the Pediatric Rheumatology Clinic, Advanced Pediatrics Centre at the Post Graduate Institute of Medical Education and Research, Chandigarh, during the period 1993–2013. Seventy-six children were diagnosed to have inflammatory myopathy during this period. Of these, 63 had JDM, 3 had polymyositis while 10 had an overlap syndrome. We had reported 2 deaths out of 33 (8.3 %) patients with JDM in 2004, and over the last 9 years, we have encountered five more deaths in this group, thereby accounting for a mortality rate of 11.1 % (7/63) over two decades of follow-up. In these five children now being described, the mean duration between onset of symptoms and institution of appropriate therapy was 9.2 months. Four children (80 %) had severe muscle weakness needing nasogastric tubes at the onset, three (60 %) had cutaneous ulcers and three (60 %) had superadded infections. Two children (40 %) had gastrointestinal vasculitis and one of these developed an intestinal perforation. Three patients (60 %) had progressive pulmonary disease and air leak was identified in two of them. Although the prognosis for survival in JDM has steadily improved, in our experience the disease remains a serious illness and still carries significant mortality in the context of a developing country.