Prognostic value of tumour-associated regulatory T-cells as a biomarker in non-small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: Tumour, nodes, and metastases (TNM) staging has been deficient in prognosticating in patients suffering from non-small cell lung cancer (NSCLC). To supplement TNM staging, this systematic review and meta-analysis aimed to evaluate the prognostic value of the regulatory T cells (Treg). METHODS: A keyword search was conducted in MEDLINE and EMBASE for full-text original human studies from any region published in English during the last 12 years. Eligible for inclusion were studies evaluating the prognostic value of the number of Treg cells in NSCLC except case studies, case series, systematic reviews, and meta-analyses. Two reviewers (one reviewer used an automation tool) independently screened the studies and assessed risk-of-bias using the Quality in Prognosis Studies (QUIPS) tool. Meta-analysis was done for studies reporting significant multivariate hazard ratio (HR). RESULTS: Out of 809 retrievals, 24 studies were included in the final review. The low number of Treg cells was found significantly associated with improved overall survival (pooled log OR, 1.646; 95% CI, 1.349, 1.944; p (2-tailed) < .001; SE, 0.1217), improved recurrence-free survival (HR, 1.99; 95% CI, 1.15, 3.46; p = .01), improved progression-free survival (pooled log OR, 2.231; 95% CI, 0.424, 4.038; p (2-tailed) .034; SE, 0.4200), and worse disease-free survival (pooled log OR, 0.992; 95% CI, 0.820, 1.163; p (2-tailed) .009; SE, 0.0135), especially when identified by forkhead box P3 (FOXP3), in any stage or non-metastatic NSCLC. CONCLUSION: A low number of Treg cells indicated better survival, suggesting its potential use as a prognostic biomarker in NSCLC. SYSTEMATIC REVIEW REGISTRATION: The protocol of this review was prospectively registered on PROSPERO on August 28, 2021, and was assigned the registration number CRD42021270598. The protocol can be accessed from PROSPERO website.

Prevalence and types of cancer in older Indians: A multicentric observational study across 17 institutions in India.

The global demographic and epidemiological transition have led to a rapidly increasing burden of cancer, particularly among older adults. There are scant data on the prevalence and demographic pattern of cancer in older Indian persons. This was a multicentric observational study conducted between January 2019 and December 2020. Data were retrieved from existing electronic databases to gather information on two key variables: the total number of patients registered with oncologists and the number of patients aged 60 years and above. The primary objective was to determine the percentage of older adults among patients with cancer served by these hospitals. Secondary objectives included understanding the prevalence of different types of cancer in the older population, and the sex- and geographic distribution of cancer in older Indian patients. We included 272,488 patients with cancer from 17 institutes across India. Among them, 97,962 individuals (36 %) were aged 60 years and above. The proportion of older adults varied between 20.6 % and 53.6 % across the participating institutes. The median age of the older patients with cancer was 67 (interquartile range, 63-72) years. Of the 54,281 patients for whom the details regarding sex were available, 32,243 (59.4 %) were male. Of the 56,903 older patients, head and neck malignancies were the most prevalent, accounting for 11,158 cases (19.6 %), followed by breast cancer (6260 cases, 11 %), genitourinary cancers (6242 cases, 10.9 %), lung cancers (6082 cases, 10.7 %), hepatopancreaticobiliary (6074, 10.7 %), and hematological malignancies (5226 cases, 9.2 %). Over one-third of Indian patients with cancer are aged 60 years and above, with a male predominance. Head and neck, breast, and genitourinary cancers are the most prevalent in this age group. Characterizing the burden of cancer in older adults is crucial to enable tailored interventions and additional research to improve the care and support for this vulnerable population.

Uniqueness of lung cancer in Southeast Asia.

Lung cancer varies between Caucasians and Asians. There have been differences recorded in the epidemiology, genomics, standard therapies and outcomes, with variations according to the geography and ethnicity which affect the decision for optimal treatment of the patients. To better understand the profile of lung cancer in Southeast Asia, with a focus on India, we have comprehensively reviewed the available data, and discuss the challenges and the way forward. A substantial proportion of patients with lung cancer in Southeast Asia are neversmokers, and adenocarcinoma is the common histopathologic subtype, found in approximately a third of the patients. EGFR mutations are noted in 23-30% of patients, and ALK rearrangements are noted in 5-7%. Therapies are similar to global standards, although access to newer modalities and molecules is a challenge. Collaborative research, political will with various policy changes and patient advocacy are urgently needed.

A Randomized, Double-Blind, Phase III Study in India for Comparing Efficacy, Safety, and PK of ZRC-3277 (Pertuzumab Biosimilar) With Perjeta® in Patients With HER2-Positive Metastatic Breast Cancer.

INTRODUCTION: To evaluate the efficacy, safety, pharmacokinetics (PK), and immunogenicity of ZRC-3277 (pertuzumab biosimilar) with Perjeta® (pertuzumab) in previously untreated patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). PATIENTS AND METHODS: This phase III, multicenter, double-blind study across 38 sites in India randomized (1:1) patients with HER2-positive MBC in either the ZRC-3277 or Perjeta® group. Both groups also received trastuzumab and docetaxel. Of 268 enrolled patients, mITT population had 243 patients (119 and 124 in the ZRC-3277 and Perjeta® groups, respectively). The primary objective was to compare the between-group objective response rate (ORR) after 6 cycles of treatment. ORR was determined by evaluating scans of computed tomography or magnetic resonance imaging following Response Evaluation Criteria in Solid Tumor (RECIST 1.1). Two-sided 95% confidence interval (95% CI) for the difference in ORR was determined to evaluate the noninferiority of ZRC-3277 to Perjeta®. The secondary outcomes included the assessment of PK, immunogenicity, and safety between the 2 groups. RESULTS: In the mITT population, 104 (87.39%) and 114 (91.94%) participants achieved the ORR in the ZRC-3277 and Perjeta® groups, respectively. For predefined -15% noninferiority margin, obtained 2-sided 95% CIs (-12.19%, 3.11%) for the difference in ORR (-4.55%) between the 2 groups demonstrated the noninferiority of ZRC-3277 to Perjeta®. PK, immunogenicity, and safety were not significantly different between the 2 groups. CONCLUSION: Efficacy, PK, immunogenicity, and safety profiles of ZRC-3277 was found to be similar to those of Perjeta®.

Efficacy and Safety of BP02 (Trastuzumab Biosimilar) in HER2-Positive Metastatic Breast Cancer: A Multicenter Phase III Study.

BACKGROUND AND OBJECTIVE: Trastuzumab targets human epidermal growth factor receptor 2 (HER2) receptors and is indicated for treating HER2-positive metastatic breast cancer. BP02, a recombinant IgG1 kappa humanized monoclonal antibody, is being developed as a trastuzumab biosimilar. The objective of this study was to evaluate the equivalence of BP02 with reference trastuzumab (RT: Herceptin®-EU) in patients with HER2-positive metastatic breast cancer. METHODS: This double-blinded, 1:1 randomized, parallel-group, active-controlled, phase III equivalence trial recruited women aged 18-75 years with histologically/cytologically confirmed HER2- positive, locally recurrent or metastatic breast cancer with systemic metastasis, from 59 sites in India. Patients were randomly allocated 1:1 stratified by estrogen receptor/progesterone receptor status to receive BP02/RT (8-mg/kg loading dose on day 1-cycle 1, 6 mg/kg on day 1-cycles 2-8, of each 3-week cycle) combined with docetaxel (75 mg/m2 on day 1-cycles 1-8) [induction phase]. Participants with complete or partial response, or stable disease at the end of the induction phase continued the study drug until disease progression/treatment discontinuation [maintenance phase]. The primary efficacy endpoint was the objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. RESULTS: Between 23 September, 2020 and 16 September, 2022, 690 patients were recruited (n = 345 each to BP02/RT). At the end of the induction phase (intent-to-treat population), a similar proportion of patients achieved an objective response rate with BP02 (n = 231 [67.0%], 95% confidence interval [CI] 62.0, 71.9) and RT (n = 238 [69.0%], 95% CI 64.1, 73.9). The 95% CI of risk difference (-2.03, 95% CI -9.15, 5.09) and 90% CI of risk ratio (0.97, 90% CI 0.89, 1.06) were within equivalence margins of ± 13% and (0.80, 1.25), respectively. Treatment-emergent adverse events leading to treatment withdrawal were reported in 2.9% and 3.2% patients with BP02 and RT, respectively. CONCLUSIONS: BP02 showed an equivalent efficacy and similar safety profile to RT at the end of 24 weeks. CLINICAL TRIAL REGISTRATION: CTRI Number: CTRI/2020/04/024456.

Treatment pattern and outcomes of leptomeningeal carcinomatosis in India - a retrospective study.

Background: Leptomeningeal carcinomatosis (LMC), the metastatic spread of cancer to the leptomeninges, is a rare complication and has a dismal prognosis. Due to limited data available on LMC from India, we conducted a country-wise audit of LMC across 15 centres in India. Methods: The current study conducted in 2020, was a retrospective, multicentric audit of adult patients (aged ≥18 years) with diagnosis of LMC and who received treatment during 2010-2020. Baseline characteristics, details related to previous treatments, cancer sites, LMC diagnosis, treatment pattern and overall survival (OS) were collected. Descriptive statistics were performed, and Kaplan Meier analysis was performed for the estimation of OS. Findings: Among the patients diagnosed with LMC (n = 84), diagnosis was confirmed in 52 patients (61.9%) and 'probable' in 32 (38.1%) patients. The three most common cause of malignancy were non-small cell lung cancer (NSCLC), breast cancer and gastrointestinal cancer with 45 (53.6%), 22 (26.1%) and 9 (10.7%) patients respectively. Intrathecal therapy was offered in 33 patients (39.3%). The most common intrathecal agent was methotrexate in 23 patients (27.4%). The median OS was 90 days (95% CI 48-128). Among tested variables, intrathecal therapy administration (hazard ratio [HR] = 0.36, 95% CI 0.19-0.68) and primary in lung (HR = 0.43, 95% CI 0.23-0.83) had a favourable impact on OS. Interpretation: Prognosis with leptomeningeal carcinomatosis is poor with a significant burden of morbidity and mortality in India. This data aims to highlight the current outcomes and facilitate further research on LMC. Funding: None.

Fludarabine melphalan versus fludarabine treosulfan for reduced intensity conditioning regimen in allogeneic hematopoietic stem cell transplantation: a retrospective analysis.

Various reduced-intensity conditioning (RIC) regimens are used to decrease toxicity while providing comparable outcomes to myeloablative regimens. We compared toxicity and outcomes between two RIC regimens, fludarabine with melphalan (Flu-Mel) and fludarabine with treosulfan (Flu-Treo), retrospectively over a 10-year period in two donor groups, matched related donor (MRD)/matched unrelated donor (MUD) and haploidentical (Haplo) transplants. The study included 138 patients, of which 105 received MRD/MUD (Flu-Mel: 94, Flu-Treo: 11) and 33 Haplo (Flu-Mel: 17, Flu-Treo: 16) transplants. In the MRD/MUD group, 44 (47%) of patients who received Flu-Mel had grade 3/4 oral mucositis compared to 1 (9%) who received Flu-Treo (P = 0.02). Corresponding numbers in the Haplo group were 7 (41%) and 1 (6%). Grade 3/4 diarrhoea was more frequent with Flu-Mel than Flu-Treo in the Haplo group (41% vs 6%; P = 0.039), but not the MRD/MUD group. Median follow-up time for all patients was 4.8 years. Five-year OS in the MRD/MUD group was 62% with Flu-Mel versus 53% with Flu-Treo (P = 0.0694). Similarly, 5-year OS was 41% with Flu-Mel and 28% with Flu-Treo (P = 0.770) in the Haplo group. Severe mucositis and diarrhoea were significantly less frequent with Flu-Treo than Flu-Mel. Flu-Treo provided comparable outcomes to Flu-Mel in all donor transplants.

Treatment of Metastatic Colorectal Cancers in Resource-Constrained Low- and Middle-Income Countries (LMICS) Scenario-Outcomes, Practice Patterns, and Commentary on Treatment Costs.

Anant RamaswamyIntroduction The overall survival (OS) of metastatic colorectal cancers (mCRCs) in clinical practice and resource-constrained low- and middle-income countries (LMICS) like India is not known. Materials and Methods Data of patients with mCRC treated between January 2013 and August 2017 were accessed from a prospectively maintained database. Demographics, disease characteristics, chemotherapeutic regimens, use of monoclonal antibodies, and survival outcomes in treated patients were collected and analyzed. Costs of treatment options as off 2017 were also interpreted. Results The data of 403 patients satisfied prespecified inclusion criteria and were included for analysis. The median age of the cohort was 48 years (range: 17-86) with a predominance of rectal cancers (63.3%), liver alone metastases (47.1%), and resected primary (69.7%). Signet ring histology was present in 82 patients (20.3%). The most commonly used first-line regimen (CT1) was modified capecitabine-oxaliplatin (53.3%). Two hundred and nineteen patients (54.3%) received second-line systemic therapy (CT2). Patients received a median of two lines of therapy (range: 1-6). MoAbs were used by 48 patients (13.4%) with CT1 and 34 patients (15.5%) with CT2. Median OS of the entire cohort was 17.61 months (95% confidence interval: 15.48-19.74), which was within the predicted range, as per investigator hypothesis. The presence of signet ring histology ( p <0.001), raised carcinoembryonic antigen at baseline ( p =0.017), and the absence of a resected primary ( p <0.001) predicted inferior median OS. Conclusions Survival of patients with mCRC in a resource-constrained LMIC scenario like India is approximately 12 to 15 months lower than published trial data. Limited access to targeted therapy and newer expensive treatment options due to financial constraints may contribute to this disparity.

A unique case of adamantinoma-like Ewing sarcoma in the calcaneus, exhibiting prominent squamous differentiation and displaying EWSR1 gene rearrangement.

Adamantinoma-like Ewing sarcoma is uncommonly reported in the skeletal sites, including small bones of the feet.A 15-year-old girl presented with pain and swelling in her left foot, leading to difficulty in walking for 8 months. Plain radiograph revealed an ill-defined, lytic-sclerotic lesion without significant periosteal reaction in her left calcaneus. Magnetic resonance imaging (MRI) revealed an expansile lesion involving the anterior calcaneus, which was hypointense on T1 and heterogeneously hyperintense on T2-weighted sequences, infiltrating the adjacent bones and soft tissues. On imaging, the differential diagnoses considered were a giant cell tumor and other primary bone tumors.Histopathological examination revealed a tumor composed of small round cells, with interspersed keratin pearls. Immunohistochemically, the tumor cells were positive for CD99/MIC2, pan-cytokeratin (AE1/AE3), p40, p63, NKX2.2, and synaptophysin. Diagnosis of adamantinoma-like Ewing sarcoma was offered on the initial biopsy. Furthermore, the tumor cells revealed EWSR1 gene rearrangement by fluorescence in situ hybridization, confirming this diagnosis. The patient underwent neoadjuvant chemotherapy, had a poor response, and finally underwent below-knee amputation.This constitutes a rare case of adamantinoma-like Ewing sarcoma in the calcaneus. Ewing sarcoma may be considered as a differential diagnosis for intraosseous lytic-sclerotic lesions, even without significant periosteal reaction, at unusual sites, such as the bones of the foot. Awareness of this entity and application of ancillary techniques is recommended for its exact diagnosis and in differentiating this rare variant from its diagnostic mimics. This case also indicates a poor chemotherapy response in this unusual variant of Ewing sarcoma, occurring in the calcaneus.

Adjuvant chemotherapy in stage II-III operated colon cancer patients from a nontrial cohort in a low colon cancer prevalence country with predominant use of modified CAPOX.

BACKGROUND: Data regarding the practice of adjuvant chemotherapy, specifically with modified CAPOX, and survival outcomes in operated colon cancer patients from a nontrial cohort in a lower-middle income and low prevalence nation like India is scarce. MATERIALS AND METHODS: Patients who underwent upfront curative resection for colon cancer from January 2013 to December 2016 were analyzed for baseline variables and outcomes. RESULTS: A total of 491 patients underwent curative resection in the predefined time period. The median age of the patients was 53 years (range: 17-87). Patients with Stage I, Stage II, and Stage III disease comprised 7.9%, 44.8%, and 45.4% of the entire cohort, respectively. Patients with Stage I cancer were observed. Adjuvant chemotherapy was planned for 384 patients (78.2%), with the doublet regimens (capecitabine-oxaliplatin, or 5-fluorouracil-oxaliplatin) being used commonly (77.6%). Common toxicities were Hand-foot syndrome (Grade 2/3 - 21.4%) and peripheral neuropathy (Grade 2/3 - 20.1%). About 85% of patients receiving monotherapy (capecitabine or 5 fluorouracil) and 81.2% of patients receiving doublet chemotherapy (mCAPOX or modified FOLFOX-7) completed their planned adjuvant treatment. With a median follow-up of 22 months, estimated 3 years event-free survival was 86%, and overall survival (OS) was 93.6%. Stage, younger age (<50 years), underlying cardiovascular abnormalities, need for dose reductions and noncompletion of planned chemotherapy predicted for inferior estimated 3-year OS on multivariate analysis. CONCLUSIONS: Adjuvant chemotherapy especially with modified CAPOX appears well tolerated in the Indian population and early survival outcomes appear to be comparable to published literature.

Outcomes with second-line chemotherapy in advanced pancreatic cancers: A retrospective study from a tertiary cancer center in India.

INTRODUCTION: Approximately 40% of patients receiving first-line chemotherapy (CT1) for advanced pancreatic adenocarcinomas (PDACs) receive second-line chemotherapy (CT2). The most appropriate regimen to be used has not been identified, and data regarding CT2 in advanced PDAC from India are scarce. MATERIALS AND METHODS: A retrospective analysis of advanced PDAC patients who were evaluated during the period of August 2013 to August 2016 in the Department of GI medical Oncology, at Tata Memorial Hospital was conducted. Patients with histologically proven PDAC and started on CT2 postprogression or recurrence after CT1 were included for analysis. RESULTS: A total of 237 patients received CT1 in the period of study, of which 76 patients (39.66%) received CT2. The median age of patients was 59.5 years (range: 38-82), majority were male (69.7%), and 14 patients (18.4%) had undergone curative pancreatic resection at baseline. The common regimens used as CT2 were modified 5 fluorouracil/leucovorin/irinotecan (mFOLFIRI) (35.5%), gemcitabine-nab paclitaxel (18.4%), and gemcitabine-erlotinib (11.8%). Common grade 3/4 toxicities noted were fatigue (10.3%), anemia (10.3%), neutropenia (7.4%), and vomiting (7.4%). Dose reductions were required in 32.9% of patients. RR, DCR, median event free survival, and median overall survival were 21.1%, 48.7%, and 5.94 months (95% confidence intervals [CI]: 4.68-7.20) and 8.08 months (95% CI: 7.11-9.07) respectively. CONCLUSIONS: CT2 in advanced PDAC appears feasible in the Indian setting if the patients are appropriately selected and they can be treated with acceptable toxicities and reasonable outcomes.

Poor Risk Advanced Renal Cell Carcinoma: Outcomes from a Registry in a Tertiary Cancer Center.

BACKGROUND: Poor-risk advanced Renal cell carcinoma (RCC) are an under-evaluated and difficult to treat subset of patients with poor prognosis. While Temsirolimus is the approved first line therapy for this category, Tyrosine kinase inhibitors (TKIs) are also commonly uses as initial treatment. We present an analysis of poor-risk advanced RCC treated in our institute. MATERIALS AND METHODS: Patients diagnosed as poor-risk (as per Heng criteria) advanced RCC from June 2008 to December 2015 were analysed for baseline demographics, treatment received, toxicity (primarily Grade 3 and Grade 4), response rates (RR) and survival. RESULTS: 60 patients (43 males, 17 females) with a median age of 53 years were included for final analysis. Median ECOG PS was 1, clear cell was the predominant histology (63.3%), and 46.7% of patients had greater than 2 sites of metastases. Sorafenib, Sunitinib, Temsirolimus and Pazopanib were used to treat 43.3%, 36.7%, 8.3% and 6.7% of patients respectively, while 3 patients were offered upfront best supportive care. Common adverse events included skin rash (31.5%), HFS (Grade 2 and 3 - 30.8%), mucositis (26.3%), hypertension (24.5%), and dyslipidaemias (22.8%). 41 patients were available for response - overall response rate observed was 15%, while clinical benefit rate was 50%. Median progression free survival was 5.78 months (4.67-6.89) and median overall survival (OS) was 10.05 months (7.31-12.79). CONCLUSION: A majority of poor-risk metastatic RCC patients in our study were treated with TKIs and the survival outcomes appear to suggest that this strategy is a feasible alternative to Temsirolimus in the Indian setting.

Patterns of Care and Clinical Outcomes in Patients With Metastatic Renal Cell Carcinoma-Results From a Tertiary Cancer Center in India.

INTRODUCTION: The current treatment of metastatic renal cell carcinoma (mRCC) revolves around targeted agents, which have resulted in a median overall survival of 22 to 26 months in registration trials. However, the outcomes in a non-trial, real-world Indian population have not yet been evaluated. MATERIALS AND METHODS: The present study was a part of a prospective Clinical Trials Registry-India-registered study, the Kidney Cancer Registry, a prospectively maintained kidney cancer registry. The data of patients with a diagnosis of mRCC from February 2007 to August 2015 who were potential candidates for systemic therapy were extracted from the database and analyzed for treatment patterns and outcomes. RESULTS: The data from 212 patients were eligible for analysis. Of these 212 patients, 204 (96.2%) received first-line systemic treatment with sunitinib (40.6%), sorafenib (37.7%), pazopanib (2.8%), temsirolimus (2.8%), or everolimus (1.9%). The risk status of 91% of the patients could be stratified using the Heng criteria into favorable (18.9%), intermediate (43.9%), and poor risk (28.3%) categories. The response rate, clinical benefit rate, median progression-free survival, and median overall survival with first-line targeted therapy were 22.5%, 60.7%, 7.09 months, and 12.87 months, respectively. The common adverse events seen included skin rash (31.7%), hypertension (29.4%), grade 3 hand-foot syndrome (27.4%), mucositis (26.4%), dyslipidemia (20%), and hyperglycemia (17.6%). Patients receiving second-line therapy (22.6%) had superior overall survival to patients who had not (16.46 vs. 10.67 months; P = .032). CONCLUSION: The present registry-based study is the first, to the best of our knowledge, of its type from India and showed that the overall outcomes in this real-world cohort appear comparable to non-trial data worldwide. An increased incidence of metabolic adverse events that require monitoring during treatment was also found.

Etiology and Outcomes of Lower Limb Ulcers in Non-Diabetic Patients, An Experience from Government Hospital in Western India.

AIM: To study the Etiology and Outcomes of Lower Extremity Ulcer in Non- Diabetic Patients. METHOD: A total number of 40 patients were collected from Rheumatology services (Department of Medicine), Venous Clinic (Department of Surgery) and Dermatology Clinic (Department of Dermatology) of a tertiary care hospital in Mumbai over a period of 48 months from January 2013 to December 2016. The study included serial recruitment of lower limb ulcer fulfilling inclusion criteria. RESULTS: Patients with lower limb ulcers presented with a wide range of pathology. Ulcers due to Vasculitis was the most common etiology (40%) and affected females predominantly (12/16). Venous ulcers were the second most common etiology and predominantly affected men (8/10). CONCLUSION: It is important to consider differential diagnosis of Vasculitic ulcer in chronic non healing ulcers as they show rapid response to treatment with immunosuppressant. If such ulcers are not promptly diagnosed and treated properly, systemic vasculitis can cause end organ damage or even endanger patient life.

Reproductive Health in Systemic Lupus Erythematosus, An experience from Government Hospital in Western India.

AIM: Systemic lupus erythematosus is an autoimmune disease which affects the reproductive health of women pertaining to disease or its treatment. However, Indian data is limited. Objective is to study menstrual disturbances and maternal and fetal outcome during pregnancy in SLE patients. METHODS: This retrospective and prospective observational study was conducted for a period of 18 months from March 2012 to September 2013 in a tertiary care hospital in Mumbai. The study included serial recruitment of SLE patients fulfilling inclusion criteria. RESULTS: Out of 52 patients studied, 13(25%) developed amenorrhea; 10 of them reversed and 3 patients developed premature menopause (5.77%). The higher mean age (30 years or more) at initiation of Cyclophosphamide therapy was associated with higher incidence of irreversible amenorrhea and this difference was statistically significant (p=0.0001). Out of 16 SLE pregnancies in 16 different patients, 9 pregnancies were successful while 7 were unsuccessful including IUFDs, abortions and maternal mortality. The incidence of successful pregnancies was significantly higher in low disease activity group (6/N=6, 100%) when compared to high disease activity group (3/N=10, 30%) (p=0.0114). CONCLUSIONS: High disease activity and Cyclophosphamide therapy are the two most important factors causing amenorrhea in SLE patients. Cyclophosphamide therapy when initiated in patients older than 30 years can lead to irreversible amenorrhea. Successful pregnancy is possible even in lupus nephritis patients if disease is well controlled at the time of conception.