Risk of relapse after anti-PD1 discontinuation in patients with Hodgkin lymphoma.

INTRODUCTION: Patients with relapsed/refractory Hodgkin lymphoma (R/R HL) experience high response rates upon anti-PD1 therapy. In these patients, the optimal duration of treatment and the risk of relapse after anti-PD1 discontinuation are unknown. METHODS: We retrospectively analyzed patients with R/R HL who responded to anti-PD1 monotherapy and discontinued the treatment either because of unacceptable toxicity or prolonged remission. A machine learning algorithm based on 17 candidate variables was trained and validated to predict progression-free survival (PFS) landmarked at the time of discontinuation of anti-PD1 therapy. RESULTS: Forty patients from 14 centers were randomly assigned to training (n = 25) and validation (n = 15) sets. At the time of anti-PD1 discontinuation, patients had received treatment for a median duration of 11.2 (range, 0-time to best response was not statistically significant in discriminating patients with PFS lesser or greater than 12 months). Considering PFS status as a binary variable (alive or dead) at a specific time point (12 months) is convenient, intuitive and allows for comparing the value of potential predicting variables in these two groups of patients. Nonetheless, this approach has two drawbacks: first, it binarizes outcome; second, it excludes patients alive with a time to last follow up lesser 12 months. Therefore, it is less powerful to demonstrate statistically significant association with PFS even if it exists 5 months. Patients discontinued anti-PD1 treatment either because of prolonged remission (N = 27, 67.5%) or unacceptable toxicity (N = 13, 32.5%). Most patients were in CR (N = 35, 87.5%) at the time of anti-PD1 discontinuation. In the training set, the machine learning algorithm identified that the most important variables to predict PFS were patients' age, time to best response, and presence or absence of CR. The performance observed in the training set was validated in the validation set. CONCLUSION: In this pilot, proof of concept study using a machine learning algorithm, we identified biomarkers capable of predicting the risk of relapse after anti-PD1 discontinuation (age, time to best response, quality of response). Once confirmed, these simple biomarkers will represent useful tools to guide the management of these patients.

Adjuvant everolimus in high-risk diffuse large B-cell lymphoma: final results from the PILLAR-2 randomized phase III trial.

Background: Patients with diffuse large B-cell lymphoma (DLBCL) with an International Prognostic Index (IPI) ≥3 are at higher risk for relapse after a complete response (CR) to first-line rituximab-based chemotherapy (R-chemo). Everolimus has single-agent activity in lymphoma. PILLAR-2 aimed to improve disease-free survival (DFS) with 1 year of adjuvant everolimus. Patients and methods: Patients with high-risk (IPI ≥3) DLBCL and a positron emission tomography/computed tomography-confirmed CR to first-line R-chemo were randomized to 1 year of everolimus 10 mg/day or placebo. The primary end point was DFS; secondary end points were overall survival, lymphoma-specific survival, and safety. Results: Between August 2009 and December 2013, 742 patients were randomized to everolimus (n = 372) or placebo (n = 370). Median follow-up was 50.4 months (range 24.0-76.9). Overall, 47% of patients were ≥65 years, 50% were male, and 42% had an IPI of 4 or 5. 48% and 67% completed everolimus and placebo, respectively. Primary reasons for everolimus discontinuation versus placebo were adverse events (AEs; 30% versus 12%) and relapsed disease (6% versus 13%). Everolimus did not significantly improve DFS compared with placebo (hazard ratio 0.92; 95% CI 0.69-1.22; P = 0.276). Two-year DFS rate was 77.8% (95% CI 72.7-82.1) with everolimus and 77.0% (95% CI 72.1-81.1) with placebo. Common grade 3/4 AEs with everolimus were neutropenia, stomatitis, and decreased CD4 lymphocytes. Conclusions: Adjuvant everolimus did not improve DFS in patients already in PET/CT-confirmed CR. Future approaches should incorporate targeted agents such as everolimus with R-CHOP rather than as adjuvant therapy after CR has been obtained. ClinicalTrials.gov: NCT00790036.

Phase II study of copanlisib, a PI3K inhibitor, in relapsed or refractory, indolent or aggressive lymphoma.

BACKGROUND: Copanlisib is a pan-class I phosphatidylinositol 3-kinase inhibitor with predominant activity against the α- and δ-isoforms. PATIENTS AND METHODS: This phase II study evaluated the response rate of copanlisib administered intravenously on days 1, 8, and 15 of a 28-day cycle, in patients with indolent or aggressive malignant lymphoma. Archival tumor tissues were used for immunohistochemistry, gene-expression profiling, and mutation analysis. RESULTS: Thirty-three patients with indolent lymphoma and 51 with aggressive lymphoma received copanlisib. Follicular lymphoma (48.5%) and peripheral T-cell lymphoma (33.3%) were the most common histologic subtypes. Most patients (78.6%) had received prior rituximab and 54.8% were rituximab-refractory. Median duration of treatment was 23 and 8 weeks in the indolent and aggressive cohorts, respectively (overall range 2-138). Eighty patients were evaluated for efficacy. The objective response rate was 43.7% (14/32) in the indolent cohort and 27.1% (13/48) in the aggressive cohort; median progression-free survival was 294 days (range 0-874) and 70 days (range 0-897), respectively; median duration of response was 390 days (range 0-825) and 166 days (range 0-786), respectively. Common adverse events included hyperglycemia (57.1%; grade ≥3, 23.8%), hypertension (54.8%; grade ≥3, 40.5%), and diarrhea (40.5%; grade ≥3, 4.8%), all generally manageable. Neutropenia occurred in 28.6% of patients (grade 4, 11.9%). Molecular analyses showed enhanced antitumor activity in tumors with upregulated phosphatidylinositol 3-kinase pathway gene expression. CONCLUSION: Intravenous copanlisib demonstrated promising efficacy and manageable toxicity in heavily pretreated patients with various subtypes of indolent and aggressive malignant lymphoma. Subtype-specific studies of copanlisib in patients with follicular, peripheral T-cell, and mantle cell lymphomas are ongoing. This trial is registered with ClinicalTrials.gov number NCT01660451 (Part A).

90Y-ibritumomab tiuxetan, fludarabine, busulfan and antithymocyte globulin reduced-intensity allogeneic transplant conditioning for patients with advanced and high-risk B-cell lymphomas.

BACKGROUND: Patients with advanced B-cell non-Hodgkin's lymphoma (NHL) refractory to initial chemotherapy or relapsing after autologous stem-cell transplantation have a poor prognosis. Allogeneic stem-cell transplantation after reduced-intensity conditioning (RIC) regimen can be a therapeutic option. However, the high incidence of relapse remains a challenging issue. We speculated that the incorporation of (90)Y-Ibritumomab tiuxetan into a fludarabine-based RIC regimen would improve the lymphoma control without overwhelming toxicity. Our aim was to evaluate the safety of (90)Y-Ibritumomab tiuxetan in association with such a regimen in a prospective multicenter phase II trial. PATIENTS AND METHODS: Thirty-one patients with advanced lymphoma from five distinct institutions were included between February 2008 and October 2010. Thirty patients in complete or partial response after failure of a median of 3 (range, 2-4) previous chemotherapy regimens including autologous transplant in 29 were evaluable for nonrelapse mortality (NRM) at day 100 post-transplant that was the primary end point. RESULTS: With a median follow-up of 32 months (range, 29-60 months), the 2-year event-free and overall survivals of the whole study group were both 80% [95 confidence interval (CI) 60.8% to 90.5%). The 100-day and 2-year post-transplant cumulative incidences of NRM were 3.3% (95% CI 0.2% to 14.9%) and 13.3% (95% CI 5.4% to 33.2%), respectively. The 2-year cumulative incidence of relapse was 6.7% (95% CI 1.7% to 25.4%). The cumulative incidences of grade II-IV and extensive chronic graft-versus-host disease were 27% and 14%, respectively. CONCLUSIONS: For chemosensitive advanced high-risk B-cell lymphoma, the addition of (90)Y-Ibritumomab tiuxetan to a RIC regimen based on fludarabine, busulfan and antithymocyte globulin followed by allogeneic transplant is safe and highly effective. clinicaltrials.gov: NCT00607854.

Combination of rituximab, bortezomib, doxorubicin, dexamethasone and chlorambucil (RiPAD+C) as first-line therapy for elderly mantle cell lymphoma patients: results of a phase II trial from the GOELAMS.

BACKGROUND: There is no consensual first-line chemotherapy for elderly patients with mantle cell lymphoma (MCL). The GOELAMS (Groupe Ouest-Est des Leucémies Aiguës et Maladies du Sang) group previously developed the (R)VAD+C regimen (rituximab, vincristine, doxorubicin, dexamethasone and chlorambucil), which appeared as efficient as R-CHOP (rituximab, cyclophosphamide, doxorubicine, vincristine, prednisone) while less toxic. Based on this protocol, we now added bortezomib (RiPAD+C: rituximab, bortezomib, doxorubicin, dexamethasone and chlorambucil) given its efficacy in relapsed/refractory MCL patients. The goal of the current phase II trial was to evaluate the feasibility and efficacy of the RiPAD+C regimen as frontline therapy for elderly patients with MCL. PATIENTS AND METHODS: Patients between 65 and 80 years of age with newly diagnosed MCL received up to six cycles of RiPAD+C. RESULTS: Thirty-nine patients were enrolled. Median age was 72 years (65-80). After four cycles of RiPAD+C, the overall response rate was 79%, including 51% complete responses (CRs). After six cycles, CR rate increased up to 59%. After a 27-month follow-up, median progression-free survival (PFS) is 26 months and median overall survival has not been reached. Four patients (10%) discontinued the treatment because of a severe toxicity and seven patients (18%) experienced grade 3 neurotoxicity. CONCLUSION: The bortezomib-containing RiPAD+C regimen results in high CR rates and prolonged PFS with predictable and manageable toxic effects in elderly patients with MCL.

Reduced-intensity conditioning allogeneic stem cell transplantation for relapsed/refractory mantle cell lymphoma: a multicenter experience.

BACKGROUND: Despite therapeutic approach that combines rituximab-containing chemotherapy, followed or not by autologous stem cell transplantation (auto-SCT), mantle cell lymphoma (MCL) patients experience relapses. Reduced-intensity conditioning allogeneic stem cell transplantation (RIC-allo-SCT) at time of relapse may represent an attractive strategy. PATIENTS AND METHODS: We report a multicenter retrospective analysis. Seventy MCL patients underwent RIC-allo-SCT in 12 centers. RESULTS: Median age at transplantation was 56 years and median time from diagnosis to transplantation was 44 months. The median number of previous therapies was 2 (range, 1-5) including autologous transplantation in 47 cases. At time of transplantation, 35 patients were in complete remission, 20 were in partial response and 15 in stable disease or progressive disease. The median follow-up for living patients was 24 months. The 2-year event-free survival (EFS) and overall survival (OS) rates were 50% and 53%, respectively. The 1- and 2-year transplant-related mortality rates were 22% and 32%, respectively. The statistical analysis demonstrated that disease status at transplantation was the only parameter influencing EFS and OS. CONCLUSIONS: These results suggest that RIC-allo-SCT may be an effective therapy in MCL patients with a chemo-sensitive disease at time of transplantation, irrespective of the number of lines of prior therapy. Studies are warranted to investigate the best type of RIC regimen.

Carmustine replacement in intensive chemotherapy preceding reinjection of autologous HSCs in Hodgkin and non-Hodgkin lymphoma: a review.

High-dose chemotherapy preceding autologous hematopoietic stem cell transplantation (auto-HSCT) is one treatment option for patients with Hodgkin (HL) or non-Hodgkin lymphoma (NHL). The most frequently used intensive chemotherapy is a combination of carmustine (BCNU), etoposide, cytarabine and melphalan (BEAM). However, BCNU is consistently in short supply, and there has been a recent dramatic increase in its cost, necessitating the utilization of conditioning alternatives. The busulfan-based conditioning regimen known as the busulfan-cyclophosphamide-etoposide (BuCyE) combination is the second most-studied conditioning regimen worldwide after BEAM, and it exhibits a benefit/risk ratio that is comparable to that of BEAM. In addition to these two combinations, the present manuscript also summarizes data reported for other conditioning combinations. Owing to the lack of prospective and comparative studies, a comparison of the toxicities and medicoeconomical profiles of these treatments is warranted to identify effective replacements for BCNU-based conditioning.

Trisomy 19 as the sole chromosomal abnormality in proliferative chronic myelomonocytic leukemia.

Distinct morphologic and clinical features associated with specific chromosomal abnormalities have been described in subgroups of myelodysplastic syndromes (MDS), which often are losses or gains and only rarely translocations. Among 103 consecutive MDS patients diagnosed and karyotyped at the Albert-Ludwigs University of Freiburg (ALU) between 1993 and 1999, two chronic myelomonocytic leukemias (CMMoL) displayed trisomy 19 (+19) as the sole chromosomal abnormality. Three further CMMoL cases with +19 as the single abnormality, two of which previously reported, were collected from other centers. Four of the five patients presented with leukocytosis and splenomegaly, and an increased number of ringed sideroblasts was observed in two cases. Treatment was low-dose Decitabine (cases 1 and 2), oral steroids (case 3), hydroxyurea (case 4), and daunorubicin/Ara-C (case 5). Transformation to acute myeloid leukemias (AML) occurred in three/five patients (cases 1, 2, and 4) 26, 12, and 22 months after diagnosis of CMMoL, respectively. We conclude that +19 as the sole anomaly is a rare but recurrent change in CMMoL, in particular of the proliferative type. It is at present unclear which gene(s) located on chromosome 19 might have a functional role for the development of this phenotype.

Splitting bone marrow trephines into frozen and fixed fragments allows parallel histological and molecular detection of B cell malignant infiltrates.

Clonality analysis of the immunoglobulin heavy chain (IgH) gene is helpful in identifying malignant B cell infiltrates in the bone marrow and is usually carried out on separate aspirates or on the same formalin-fixed decalcified bone marrow specimen. To determine whether the removal of the decalcification step would improve the molecular analysis, we first studied 12 bone marrow specimens with lymphoma infiltration split into a fixed and a small frozen fragment. Both the detection rate of IgH gene monoclonality and DNA quality were found to be superior in the frozen part than in the fixed part. Conversely, to evaluate whether the split would compromise histological analysis, we selected a series of 134 bone marrow specimens obtained from patients with small B cell lymphoma and showing IgH monoclonality on the frozen part. The histological detection rate of infiltrated or suspicious infiltrates (95%) on the fixed part was not altered by saving a frozen part.

Lenalidomide with or without erythropoietin in transfusion-dependent erythropoiesis-stimulating agent-refractory lower-risk MDS without 5q deletion.

After failure of erythropoiesis-stimulating agents (ESAs), lenalidomide (LEN) yields red blood cell (RBC) transfusion independence (TI) in 20-30% of lower-risk non-del5q myelodysplastic syndrome (MDS). Several observations suggest an additive effect of ESA and LEN in this situation. We performed a randomized phase III study in 131 RBC transfusion-dependent (TD, median transfusion requirement six RBC units per 8 weeks) lower-risk ESA-refractory non-del5q MDS. Patients received LEN alone, 10 mg per day, 21 days per 4 weeks (L arm) or LEN (same schedule) + erythropoietin (EPO) beta, 60,000 U per week (LE arm). In an intent-to-treat (ITT) analysis, erythroid response (HI-E, IWG 2006 criteria) after four treatment cycles (primary end point) was 23.1% (95% CI 13.5-35.2) in the L arm and 39.4% (95% CI 27.6-52.2) in the LE arm (P=0.044), while RBC-TI was reached in 13.8 and 24.2% of the patients in the L and LE arms, respectively (P=0.13). Median response duration was 18.1 and 15.1 months in the L and LE arms, respectively (P=0.47). Side effects were moderate and similar in the two arms. Low baseline serum EPO level and a G polymorphism of CRBN gene predicted HI-E. Combining LEN and EPO significantly improves erythroid response over LEN alone in lower-risk non-del5q MDS patients with anemia resistant to ESA.

[Management of acute coronary syndromes in a new French coronary intensive care unit. The first four years of activity in the GRACE registry (Global Registry of Acute Coronary Events)]. / Evaluation des quatre premières années d'activité d'une unité de soins intensifs cardiologiques pour la prise en charge des syndromes coronaires aigus comparativement aux données régionales du registre GRACE (Global Registry of Acute Coronary Events).

UNLABELLED: The GRACE registry provides the opportunity to analyse management of acute coronary syndromes in the real word and the impact of hospital characteristics. In this setting, we compare the activity of a new coronary intensive care unit with regional data. METHODS: From January 2000 to December 2003, 376 eligible patients were involved (22% of regional inclusion). GRACE standard diagnosis were the following, for our centrer (for the cluster): ST elevation myocardial infarction 28% (37%), non-ST elevation myocardial infarction 32% (31%), unstable angina 33% (24%). Demographic characteristics were similar with a median age of 64 (vs 66) and a large majority of male (74 vs 81%). Medical history and cardiovascular risk factors were comparable. Predictors of hospital mortality were observed at the same rate: cardiogenic shock (3 vs 3%), congestive heart failure > Killip 2 (4 vs 4%), left ventricular ejection fraction (LVEF) lower than 40% (17 vs 16%), recurrent ischemic symptoms (8 vs 8%). Coronary artery bypass grafts were required in 5% (vs 2%). RESULTS: Drugs prescription rates were similar: aspirin at admission (95%) and at discharge (95%), betablocker at admission (70%) and at discharge (85%), statin at admission (< 30% in 2000, > 60% in 2003) and at discharge (< 60% in 2000 and > 80% in 2003), ticlopidin-clopidogrel at admission (< 20% in 2000 and > 40% in 2003), ACE inhibitor for LVEF < 40%, intravenous GPIIblIIa, and low molecular weight heparin (90%). Cardiac catheterisation (90%) and percutaneous coronary interventions (80%) were performed at the same rates in our center and in the cluster. Hospital death was similar (2 vs 4%). Discharge status was home for a large majority of patients (63 vs 76%). The median length of stay was five days and shorter than three days for patients with unstable angina. CONCLUSION: Based on GRACE registry data, the present evaluation revealed that our new center offered evidence-based medical and interventional therapy in patients with acute coronary syndromes at the same level than experienced institutions with similar results for hospital death and length of stay.

[Polycythemia vera revealed by Wells syndrome]. / Maladie de Vaquez révélée par un syndrome de Wells.

BACKGROUND: Wells syndrome is an eosinophilic dermatosis that is mainly reported in association with infections or insect bites, and more rarely during haematological disorders. CASE REPORT: A 32 year-old woman presented several recurrent episodes of massive swelling and erythema papulo-nodular inflammatory plaques on the buttocks that spontaneously resolved. The biopsy revealed marked infiltration of the dermis with eosinophils suggesting Wells syndrome. Examination found an isolated hepatosplenomegaly with true polycythemia and a myeloproliferative disorder. The diagnosis of Vaquez disease was made. DISCUSSION: Wells syndrome is a distinctive disease entity with a wide polymorphism of clinical and histological features, unspecific, and varying depending on the age of the lesions. Various triggering factors are involved, but this syndrome may also reveal hematological disorders. Cutaneous manifestations often occur before the hematological diagnosis, but are frequently misdiagnosed. Only two other cases of Wells syndrome associated with Vaquez disease have been reported. Our case report underlined the importance of systematic research for an hemopathy in Wells syndrome, especially in young patients.

Intrapleural administration of streptokinase in complicated purulent pleural effusion: a CT-guided strategy.

OBJECTIVE: To determine the usefulness and the results of a strategy using intrapleural streptokinase (SK) instillation guided by repeated computed tomography (CT) scan examinations in pleural empyemas unresponsive to chest tube drainage. DESIGN: A retrospective chart review. SETTING: The medical Intensive Care Unit and Department of Radiology, in a university hospital. PATIENTS: Sixteen patients with empyema who had a persistent pleural effusion despite drainage, among 37 patients with infectious pleural effusion. INTERVENTIONS: In the 16 patients, CT examination was performed before and at least once after SK. Intrapleural SK was instilled, either through the chest tube or via a needle puncture, according to the CT scan results. RESULTS: The first CT scan confirmed a persistent effusion in all, showing a multiloculated effusion in 13 patients, and an ectopic loculus in one. The first SK instillation resulted in a dramatic increase of fluid drained per day (from 68 +/- 28 ml to 567 +/- 262 ml; p < 0.001), leading to complete resolution in 11 patients, while the others required a second CT scan-guided procedure. In one, the chest tube was misplaced, while in two, transparietal injection was needed. Finally, a complete resolution was observed in 14 (87.5%) of the patients. Two patients had a poor initial response to SK and were eventually scheduled for video-thoracoscopy. A single episode of chills and fever was observed among 32 SK instillations. CONCLUSION: CT-guided SK instillation in pleural empyema appears to be safe, and allowed complete resolution in 87.5% of our patients.

[Coronary subclavian steal syndrome after internal mammary artery bypass grafting. A cause of severe postoperative recurrent myocardial ischemia]. / Syndrome de vol coronaire sous-clavier après pontage mammaire interne gauche sur l'artère interventriculaire antérieure. Une cause d'ischémie myocardique résiduelle sévère postopératoire.

A 65-year-old underwent a triple bypass: internal artery mammary-descending coronary artery, aorta diagonal-lateral coronary (sequential). Three weeks later he started to have severe angina pectoris with ST depression in anterior EKG leads. A left transradial coronary angiography was performed. The examination showed a total occlusion of the left subclavian artery 2 cm after the aortic arch and a retrograde flow in the internal mammary artery (IMA). Via transfemoral approach, angiography showed the patency of the aorto-veinous sequential graft and a retrograde flow through anastomosis in the left mammary artery. The patient underwent a reimplantation of the IMA on the brachiocephalic artery. One month later the patient is doing well without chest pain. A coronary subclavian steal syndrome should be suspected in case of recurrent ischaemia after IMA bypass, particularly if there is more than 20 mmHg systolic pressure differential between the arms. Left transradial approach achieved diagnostic in case of total left subclavian artery occlusion.

[Iatrogenic dissection of the left main artery treated by direct stenting]. / Dissection iatrogène du tronc commun traitée par direct stenting.

A 70-year-old woman was referred to the department due to a symptomatic severe calcific-aortic stenosis. During pre-operative trans-radial approach coronagraphy occurred a iatrogenic dissection of the left main artery with total occlusion and cardiac arrest (asystole). Successful resuscitation is achieved with an emergency strategy of percutaneous direct stenting revascularization combined with cardiopulmonary resuscitation manoeuvres.

[Ventricular arrhythmia and halofantrine intake. Probable deleterious effect. Apropos of 3 cases]. / Arythmies ventriculaires et prise d'halofantrine. Effet délétère probable. A propos de 3 observations.

Incidence and malignant forms of imported Plasmodium falciparum malaria are increasing, and chemoprevention is more and more replaced by stand-by treatment and radical cure in preventing access on return from malaria areas. Halofantrine is recommended for this radical cure: it's an habitually well-tolerated amino-alcohol with very few side-effects. We report three cases of long QT-interval due to halofantine: three different young women coming back from Africa took halofantrine (500 mg (2 tablets) six hourly for three doses on the first and the seventh day) and all presented with syncopal episodes. Serum electrolyte concentrations and echocardiograms were normal. In one case only, a diagnosis of Plasmodium falciparum malaria was made, without severe manifestations, and in the two other cases, treatment was a radical cure. In two cases, several bursts of torsades de pointes ventricular tachycardia due to halofantrine were proven and electrophysiological cardiac tests concluded that they had a congenital long QT-interval/Romano-Ward syndrome). So far halofantrine cardiac toxicity was unknown with single dose of 24 mg/kg/d. This phenomenon can be very severe in case of preexisting cardiopathy. In spite of the rarity on the congenital Romano-Ward syndrome, systematic electrocardiogram is necessary before giving halofantrine.

[A rare etiology of spinal cord compression: Gaucher disease]. / Une étiologie rare de compression médullaire: la maladie de Gaucher.

Gaucher's disease is a sphingolipidosis transmitted as an autosomal trait. Bone lesions are frequent in type 1 of the disease (i.e. the adult type without neurological manifestation). We report the case of a 70-year old woman suffering from spinal lesions with vertebral collapse and spinal cord compression. Our diagnosis was based on the finding in bone samples of Gaucher cells looking like large macrophages, and on the enzymatic assay of glucocerebrosidase. New treatments, such as replacement of the deficient enzyme by placental glucocerebrosidase, are currently being evaluated.

[Cardiac complications of halofantrine: continuous electrocardiographic study (holter) in 20 patients]. / Complications cardiaques de l'halofantrine: etude électrocardiographique continue (holter) chez 20 patients.

Three cases of long QT-interval due to halofantrine were documented in 1992 in France. Two of them had a congenital long QT-interval (Romano-Ward syndrome). We performed a prospective study of cardiac monitoring in 20 patients taking halofantrine. Minimal ECG changes were noted with lengthening of the QT-interval. Systematic ECG is necessary before giving halofantrine.