Anticoagulation prophylaxis reduces venous thromboembolism rate in adult acute lymphoblastic leukaemia treated with asparaginase-based therapy.

Venous thromboembolism (VTE) is a well-known complication in adults receiving asparaginase (ASNase)-based intensification chemotherapy for acute lymphoblastic leukaemia (ALL). The optimal preventative strategy is unclear. Our objective is to determine the effects of low-molecular-weight heparin (LMWH) as primary VTE prophylaxis. A single-centred retrospective cohort study of adult patients with Philadelphia chromosome negative (Ph-) ALL who received ASNase-based intensification from 2001 to 2017, with prophylaxis given from 2011 to 2017. In all, 214 patients were included in this study with 99 in the historical control group and 125 in the prophylaxis group. The mean (range) enoxaparin dose was 0·79 (0·39-1·2) mg/kg. Of the 125 patients in the prophylaxis group 17 (13·6%) developed VTE during the intensification phase, while 27/99 patients (27·3%) in the control cohort experienced at least one thrombotic event (odds ratio [OR] 0·42, 95% confidence interval [CI] 0·21-0·83). Overall, the main sites of VTE incidences included deep vein thrombosis in the lower extremity (54·6%), pulmonary embolism (13·6%) and catheter-related thrombosis (22·7%). In addition, we found that after adjusting for age, T-phenotype ALL was associated with VTE development (OR 3·07, 95% CI 1·04-9·08). There was no documented major bleeding in the prophylaxis group. LMWH prophylaxis reduced the incidence of symptomatic VTE in adult patients with ALL receiving intensification chemotherapy with ASNase.

Universal venous thromboembolism policy is effective but may not adequately protect hospitalized cancer patients with larger BMI.

Routine VTE prophylaxis is recommended for hospitalized patients, but its effectiveness and safety in cancer patients is unclear. By observation, larger patients seemed poorly covered by the prophylaxis policy. The effectiveness and safety of VTE prophylaxis policy in the hospitalized patients, their potential risk factors such as BMI were examined. A retrospective chart review was conducted to determine VTE incidences, risk factors for VTE and major bleeding events between 2007 and 2016 on the solid tumor units (STU). Patients were divided into pre-policy (Pre-2012) or post-policy implementation groups (Post-2012). Descriptive statistics were used to evaluate effectiveness and safety of prophylaxis, while propensity score matching (1:3, VTE:Non-VTE) was used to reduce selection bias. The VTE incidence per patient was 1.30% (57/4392) pre-policy and 0.56% (18/3210) post-policy (p value = 0.0013). After propensity score matching, a reduction (32.3%) of VTE cases was observed after policy implementation (OR = 0.677, p = 0.32). BMI was found to be a significant predictor of VTE (OR = 1.094, 95% CI 1.021-1.172, p = 0.011). Between July 2014 and July 2016, 1.7% (19/1091) patients who received anticoagulants had a documented bleeding event. The policy positively impacted VTE events on the STU. A significant predictor of VTE was BMI and patients with high BMI may pose a risk of breaking through standard VTE prophylaxis dosing. There was no reported major bleeding for patients who developed an VTE event despite receiving prophylaxis in either the pre-policy or post-policy phase of the study, although a low incidence of minor bleeding was documented in the post-phase.

A phase II open-label study of aprepitant as anti-emetic prophylaxis in patients with acute myeloid leukemia (AML) undergoing induction chemotherapy.

Despite the widespread use of 5-HT3 antagonists as anti-emetic prophylaxis in patients with acute myeloid leukemia (AML) receiving induction chemotherapy, nausea and vomiting persist in many cases. We performed a Phase II single-arm study evaluating the use of aprepitant on days 1-5, in combination with a 5-HT antagonist on days 1-3, in AML patients undergoing induction chemotherapy with daunorubicin on days 1-3 plus cytarabine, given as a continuous infusion, on days 1-7. This was compared to a retrospective cohort of AML patients that received the same chemotherapy regimen with a 5-HT antagonist but without aprepitant. The cumulative incidence of vomiting/retching by the end of day 5 was significantly lower in the aprepitant vs. the control group (26.3 vs. 52.8%, p = 0.013). The cumulative incidence of nausea by the end of day 5 was 61% in the aprepitant group vs. 75% in the control group. The total use of supplemental anti-emetics on days 2-5 was also significantly lower in the aprepitant group (p = 0.01). In contrast, the cumulative incidence of vomiting/retching by the end of day 8, the incidence of vomiting/retching on days 6-8, and the use of anti-emetics on days 6-8, were not significantly different between the two groups. The results suggest that the use of aprepitant may be associated with a lower rate of emesis during aprepitant dosing days, but not afterward. However, this requires confirmation in a randomized trial.

Stability of sodium bicarbonate injection 8.4% in syringes over a six-week period in refrigerated temperature.

Background Dysfunctional central venous catheter prohibits the administration of potential life-saving chemotherapy and the delivery of essential supportive care needs to patients. Sodium bicarbonate injection has been shown to impede against fibrin clot formation and prolong prothrombin time and thrombin clotting time. Sodium bicarbonate injection has been tried as a second-line agent with good results in a small number of patients (internal data not published) when alteplase failed. We assessed whether the pre-filled sodium bicarbonate injection in 5 mL syringes would not only preserve sterility and retain its pH and concentration but also amount to the potential cost savings for future use when stored in a refrigerated environment. Methodology Twelve pre-filled 5 mL syringes were prepared aseptically, of which four each were tested for pH, sodium bicarbonate injection concentration and sterility when stored in refrigerated temperature over a six-week period. A standard pH meter, enzymatic carbon dioxide analyzer, and a 14-day incubation for microbial detection were employed for this study. Results Sodium bicarbonate concentration measured in the form of carbon dioxide ranged from 923 mmol/L or (1846 mosol/L) to 1006 mmol/L or (2012 mosmol/L), and pH ranged from (7.88 to 8.05) were reported over the duration of the study period. The 14-day incubation period resulted in no microbial growth. Conclusion Our study results have indicated that the pH and sodium bicarbonate injection concentration values were stable and within range, comparable to those reported by the manufacturer within the study period. The contents of the subdivided sodium bicarbonate injection 5 mL syringes retained sterility over a 14-day incubation period.

Managing skin toxicities related to panitumumab.

BACKGROUND: Dermatologic toxicities from targeted agents such as panitumumab can interfere with cancer treatment. OBJECTIVE: We sought to evaluate the rash assessment and management in a consecutive patient cohort who received panitumumab for colorectal cancer treatment. METHODS: This was a retrospective chart review. RESULTS: Skin toxicity, consisting of papulopustular rash, was experienced by 32 of 34 patients. The majority (85%) developed the rash by the end of the second infusion cycle. Patients presented with a mild (41%), moderate (38%), and severe (21%) rash, and progressed to an extensive rash without appropriate treatment. A grading system was used for 65% of patients to document severity. LIMITATIONS: Small sample size limited power in analysis. Rash severity had to be inferred based on rash description and management in 11 of the patients. CONCLUSION: Dermatologic toxicities related to panitumumab are common; however, the way they are reported and managed varies among physicians. To prevent progression, toxicities must be assessed and treated early and aggressively, according to severity grading. Dermatologists could aid oncologists in choosing the best management strategies.

Serum voriconazole level variability in patients with hematological malignancies receiving voriconazole therapy.

INTRODUCTION: Voriconazole plasma concentrations have been correlated with oral dosing in healthy subjects, but have been poorly characterized in ill patients with hematological malignancies receiving intensive chemotherapy. METHODS: The relationship between orally administered voriconazole, plasma concentrations and liver toxicity was examined in a cohort of 69 primarily acute leukemia patients undergoing intensive chemotherapy. RESULTS: Oral administration of voriconazole was associated with significant interpatient variability, with voriconazole steady-state concentrations ranging from 0 µg/mL to 16.6 µg/mL. Approximately 20% of patients achieved steady-state concentrations <1 µg/mL. When adjusted for weight, patients receiving higher voriconazole doses tended toward higher plasma concentrations; however, there was no significant relationship between the plasma concentration and genotype, age, sex or use of concomitant proton pump inhibitors. Voriconazole concentrations were correlated with higher serum alkaline phosphatase levels at day 6 to 8, and with higher bilirubin and aspartate aminotransferase levels at day 14 to 16, but not with other liver enzyme levels. CONCLUSION: In ill patients with acute leukemia and related disorders undergoing treatment with oral voriconazole, there is a poor correlation between the voriconazole dose and plasma concentrations, and many patients achieve levels that are considered to be subtherapeutic. The findings support the routine use of therapeutic drug monitoring in these patients.

INTRODUCTION: Les concentrations plasmatiques de voriconazole sont corrélées avec les doses orales chez les sujets en santé, mais sont mal caractérisées chez les patients malades atteints d'une hémopathie maligne sous chimiothérapie intensive. MÉTHODOLOGIE: Les chercheurs ont examiné le lien entre le voriconazole administré par voie orale et la toxicité hépatique dans une cohorte de 69 patients atteints surtout de leucémie aiguë sous chimiothérapie intensive. RÉSULTATS: L'administration de voriconazole par voie orale s'associait à une importante variabilité interpatient, les concentrations à l'état stable oscillant entre 0 µg/mL et 16,6 µg/mL. Environ 20 % des patients ont obtenu des concentrations à l'état stable de moins de 1 µg/mL. Après rajustement selon le poids, les patients qui receviaent des doses plus élevées de voriconazole avaient tendance à présenter des concentrations plasmatiques plus élevées. Cependant, on ne constatait aucun lien significatif entre la concentration plasmatique et le géno-type, l'âge, le sexe ou l'utilisation concomitante d'inhibiteurs de la pompe à protons. Les concentrations de voriconazole étaient corrélées avec des taux de phosphatase alcaline sérique plus élevés les jours 6 à 8 et à des taux de bilirubine et d'aspartate aminotransférase plus élevés les jours 14 à 16, mais pas à d'autres taux d'enzymes hépatiques. CONCLUSION: Chez les patients malades atteints d'une leucémie aiguë et de troubles connexes qui suivent un traitement au voriconazole par voie orale, la corrélation entre la dose de voriconazole et les concentrations plasmatiques est faible, et de nombreux patients obtiennent des taux considérés comme subthérapeutiques. Les observations soutiennent une pharmacovigilance systématique chez ces patients.

Therapeutic drug monitoring for triazoles: A needs assessment review and recommendations from a Canadian perspective.

Invasive fungal infections cause significant morbidity and mortality in patients with concomitant underlying immunosuppressive diseases. The recent addition of new triazoles to the antifungal armamentarium has allowed for extended-spectrum activity and flexibility of administration. Over the years, clinical use has raised concerns about the degree of drug exposure following standard approved drug dosing, questioning the need for therapeutic drug monitoring (TDM). Accordingly, the present guidelines focus on TDM of triazole antifungal agents. A review of the rationale for triazole TDM, the targeted patient populations and available laboratory methods, as well as practical recommendations based on current evidence from an extended literature review are provided in the present document.

Les infections fongiques invasives sont responsables d'une morbidité et d'une mortalité importantes chez les patients atteints d'une maladie immunodépressive. L'ajout des nouveaux triazoles aux traitements antifongiques a élargi le spectre d'activité et la flexibilité d'administration. Au fil des ans, leur utilisation clinique a suscité des inquiétudes quant au degré d'exposition au médicament selon une posologie approuvée standard, ce qui soulève la nécessité de la pharmacovigilance thérapeutique (PVT). Les présentes lignes directrices portent donc sur la PVT des antifongiques triazolés. Dans le présent document sont exposées une analyse de la raison d'être de la PVT des triazoles, les populations de patients ciblées et les méthodes de laboratoire offertes, de même que des recommandations pratiques fondées sur des données probantes à jour tirées d'une analyse bibliographique approfondie.

The pharmaceutical stability of trastuzumab after short-term storage at room temperature assessed by analytical techniques and tumour imaging by microSPECT/CT.

We report the pharmaceutical stability of trastuzumab stored for a short time (12 h) at room temperature (RT; 20-25 °C) compared to trastuzumab stored at 2-8 °C. The physicochemical properties were evaluated by UV-visible and FTIR spectroscopy, SDS-PAGE and size-exclusion HPLC (SE-HPLC). Trastuzumab was reacted with benzylisothiocyanate diethylenetriaminepentaacetic acid (BzDTPA) to complex 111In. The HER2-binding affinity of 111In-BzDTPA-trastuzumab synthesised from trastuzumab stored at RT or at 2-8 °C was measured using HER2-positive SK-Br-3 human breast cancer (BC) cells. The tumour and normal tissue uptake of 111In-BzDTPA-trastuzumab was studied by microSPECT/CT imaging and biodistribution studies in CD1 athymic mice with s.c. HER2-positive SK-Ov-3 human ovarian cancer xenografts. There were no differences in λmax or molar absorptivity (ε) values in the UV-visible spectra of trastuzumab stored at RT or at 2-8 °C. FTIR spectroscopy suggested no differences in secondary structure. SDS-PAGE revealed protein bands corresponding to the expected molecular weights. SE-HPLC showed identical properties for trastuzumab stored at RT or at 2-8 °C. The dissociation constant (Kd) for binding of 111In-BzDTPA-trastuzumab to HER2 on SK-Br-3 cells (2.2-4.4 nM) was not significantly different when the radioimmunoconjugates were synthesised from trastuzumab stored at RT or at 2-8 °C. MicroSPECT/CT demonstrated high uptake in SK-Ov-3 tumours in mice that was not significantly different using trastuzumab stored at RT or at 2-8 °C (33.7 ± 8.8% vs. 22.2 ± 8.1% i.d./g, respectively; P = 0.36). There were no significant differences in normal tissue uptake or in tumour/normal tissue (T/NT) ratios. We conclude that short-term storage of trastuzumab at RT for 12 h did not affect the physicochemical or biological properties of the drug.

Examining the safety and efficacy of a chemotherapy dosing method in Allogeneic Stem Cell Transplant patients of extreme body size.

BACKGROUND: There is no consensus on a universal dosing method for calculating high-dose chemotherapy in allogeneic Stem Cell Transplant (SCT) patients. The Metropolitan Life (Met-Life) Insurance Company's weight-height tables have been used to determine body weight for chemotherapy dosing for SCT, however no formal study has been done to determine if the Met-Life weight- height tables can be used for chemotherapy dosing in SCT. We retrospectively studied the use of Met-Life weight-height tables for chemotherapy dosing in SCT. Our goal is to determine if patients with extremes of body size who had undergone an SCT and were dosed according to the Met-Life weight- height tables had an increase of Treatment Related Morbidity (TRM) or mortality or relapse. PATIENTS AND METHODS: Patients were grouped into three different treatment regimens, cyclophosphamide/TBI, busulphan/cyclophosphamide, and AraC/cyclophosphamide/TBI. Patients in each treatment regimen were further divided into five equal groups based on weight. Treatment related morbidity and mortality was evaluated by comparing the lowest and highest quintiles to the middle quintiles within each treatment regimen. RESULT: Data from 262 patients was evaluated in this study. Overall, there was not an increase in TRM or mortality or in relapse in patients with extremes of body size. CONCLUSION: The Met-Life weight-height tables could be used to dose patients undergoing allogeneic SCTs. Additional prospective studies would need to be done comparing other chemotherapy dosing methods with the Met-Life weight-height tables to further validate this conclusion.

Recurrent Body Rash Warranted Second Desensitization With Acyclovir in a Myeloma Patient: A Case Report.

A 75-year-old woman developed a moderately severe rash about a week and a half after the start of bortezomib (Btb)-based chemotherapy for IgG lambda multiple myeloma; at the time, she was also receiving acyclovir as antiviral prophylaxis in addition to herpes zoster (HZ) vaccination. HZ reactivation rate is high in Btb recipients; therefore, the timing of antiviral prevention is critical in relation to Btb. Attempts were made to identify the offending agent based on the timing of drugs administered and the appearance of skin lesions in relation to other drugs. Both Btb and acyclovir were potential culprits. However, the timing of rash presented on days 9 - 10 revealed the offending agent when the corticosteroid was weaned off while acyclovir continued. A decision was made to administer acyclovir rapid desensitization program (RDP) for our patient.

Chemical Stability of Plerixafor after Opening of Single-Use Vial.

BACKGROUND: The addition of the immunostimulant plerixafor to the current standard-of-care regimens of granulocyte colony-stimulating growth factor with or without chemotherapy has improved clinical results in terms of successful stem cell mobilization and the outcomes of stem cell transplant in various settings. With this medical innovation has come an added financial cost for institutions where stem cell transplants are routinely performed, and there may be a further financial burden when the contents of partial vials of the drug are wasted, given that plerixafor vials (Mozobil, Sanofi-Aventis Canada Inc) are currently deemed suitable only for single use. OBJECTIVE: To determine whether the portion of plerixafor remaining in an opened vial of the Mozobil product after administration of a single dose is chemically stable, by comparison with the original product. METHODS: Stability testing of partial drug contents of an opened vial, stored at room temperature or under refrigeration (4°C), was conducted using liquid chromatography-tandem mass spectrometry analysis. The mean concentration of plerixafor (µmol/L), standard deviation, coefficient of variation, and bias were determined on days 2, 3, 11, 17, 24, and 31. Method validation included determination of precision, sensitivity, recovery, dilution linearity, and carryover. RESULTS: Throughout the 4-week testing period, measured plerixafor concentration in aliquots stored at room temperature and under refrigeration, tested in series over time, appeared similar. The mean residual drug concentration after initial opening was slightly, but not significantly, higher for the sample designated for storage at room temperature than the one designated for refrigerated storage (40.4 versus 39.9 µmol/L; p = 0.37). CONCLUSIONS: Residual plerixafor after initial opening of a vial of the Mozobil product remained chemically stable for at least 2 weeks both at room temperature and under refrigeration. The results of this study provide in vitro evidence to support multiple uses, instead of single use, of vials of this drug in an aseptic, controlled environment.

CONTEXTE: L'ajout de l'immunostimulant plérixafor aux traitements reconnus comme la norme de soins actuelle quant au facteur de stimulation des colonies de granulocytes, accompagné ou non de chimiothérapie, a amélioré les résultats cliniques de mobilisation des cellules souches et les résultats de greffe de cellules souches dans différents contextes. Cela dit, avec cette innovation médicale vient un poids financier supplémentaire pour les établissements où l'on exécute couramment des greffes de cellules souches. En outre, comme les fioles de plérixafor (Mozobil, Sanofi-Aventis Canada Inc.) sont présentement jugées adéquates pour un usage unique seulement, l'excédent de médicament gaspillé peut représenter une dépense additionnelle. OBJECTIF: Déterminer si ce qui reste de Mozobil dans une fiole ouverte après l'administration d'une dose unique est chimiquement stable comparativement au produit de départ. MÉTHODES: Une étude de stabilité du contenu partiel d'une fiole de médicament ouverte, entreposé à température ambiante ou conservé au réfrigérateur (4°C), a été réalisée par chromatographie en phase liquide couplée à la spectrométrie de masse en tandem. La concentration moyenne de plérixafor (µmol/L), l'écart-type, le coefficient de variation et le biais ont été établis aux jours 2, 3, 11, 17, 24 et 31. La méthode de validation comprenait la détermination de : la précision, la sensibilité, la récupération, la limite de linéarité et la contamination inter-échantillons. Résultats :Tout au long des quatre semaines d'analyse, les concentrations mesurées des aliquotes de plérixafor, entreposées à température ambiante ou conservées au réfrigérateur et analysées en séries chronologiques, semblaient similaires. Les concentrations moyennes de médicament restant après l'ouverture initiale étaient légèrement plus élevées lorsqu'entreposées à température ambiante (40,4 µmol/L) que lorsque réfrigérées (39,9 µmol/L) (p = 0,37), mais pas de façon significative. CONCLUSIONS: Le plérixafor résiduel, après l'ouverture initiale des fioles de Mozobil, demeurait chimiquement stable pendant au moins deux semaines, qu'il soit entreposé à température ambiante ou conservé au réfrigérateur. Les résultats de la présente étude offrent des données in vitro qui soutiennent une utilisation multiple, plutôt qu'un usage unique, des fioles de ce médicament en milieu aseptique contrôlé.

Lenalidomide Desensitization in Systemic Light-Chain Amyloidosis With Multi-Organ Involvement.

Limited therapeutic options are available to amyloid patients treated with many lines of therapy. Although combination therapy using lenalidomide and dexamethasone is an effective sequential regimen for systemic amyloidosis (AL), dexamethasone is often poorly tolerated in patients with cardiac involvement. Lenalidomide as single agent has modest activity, but when used in combination with dexamethasone, careful titration is needed. Dermatological adverse reactions can be problematic to patients on lenalidomide-based therapy. Lowering lenalidomide doses have not been able to consistently prevent recurrent skin toxicity. We report a patient who was neither eligible for stem cell transplant nor able to tolerate previous lines of therapy. Therapeutic dilemma arose from lenalidomide-related moderately severe skin toxicity. We enrolled the patient in the lenalidomide rapid desensitization program (RDP) with success in the presence of poor cardiac reserve and renal impairment. No recurrence of skin rash was observed during the course of therapy. To the best of our knowledge, this was the first AL patients who received and tolerated RDP well, despite multi-organ impairments. The target dose may be achieved based on individual patient's ability to tolerate RDP. Incremental dose increase can be applied in future dates without risk of rash recurrence.

Bridging efforts to longitudinally improve and evaluate VEnous thromboembolism prophylaxis uptake in hospitalized cancer patients through Interprofessional Teamwork (BELIEVE IT): a study by Princess Margaret Cancer Centre.

INTRODUCTION: Despite demonstrable risk of venous thromboembolism (VTE), thromboprophylaxis continues to be underutilized in hospitalized cancer patients. Our study evaluated institutional VTE prophylaxis rates after devising a series of strategic interventions to longitudinally improve adherence rates over a period of eight years. METHODS AND MATERIALS: Between 2004 and 2012, a series of interventions were implemented to improve the thromboprophylaxis rate among patients with solid tumours hospitalized at our institution using quality improvement methodology. Interventions included development of guidelines and institutional policies coupled with educational in-services for physicians, nurses and pharmacists and engagement of the Cancer Quality Committee. Thromboprophylaxis rates were monitored to assess response to interventions. RESULTS: At the outset in 2004, 11 of 57 (19.3%) eligible patients received appropriate pharmacological prophylaxis and formed the baseline of our analysis. Post-2009 policy implementation and educational sessions, 46.5% of an eligible 185 inpatients were administered thromboprophylaxis. Following a two-year grace period to allow for policy acceptance, three audits were conducted in 2011 for which an average prophylaxis rate of 62.3% resulted. In 2012, following another round of educational sessions, a 96.7% rate was achieved and maintained ten weeks later. Minimal bleeding risk was observed during this eight year initiative. CONCLUSION: A reproducible 96.7% prophylaxis uptake rate was the result of our perseverance and persistence in believing that culture change was inevitable through continuously collaborating with stakeholders at all levels.

Pharmacist's Role in Improving Medication Safety for Patients in an Allogeneic Hematopoietic Cell Transplant Ambulatory Clinic.

BACKGROUND: Patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT), supported by complex drug regimens, are vulnerable to drug therapy problems (DTPs) at interfaces of care after discharge from hospital and may benefit from timely pharmacy interventions and education. OBJECTIVE: To determine the effect on medication safety of, as well as potential barriers to, incorporating a pharmacist in the multidisciplinary team of an allo-HCT clinic. METHODS: Two pharmacists rotated to attend the allo-HCT clinic of a tertiary care, university-affiliated cancer centre between January and June 2010 (coverage for 1 of 3 clinic days per week). For every patient who was seen by a pharmacist, all discharge medications were reconciled from the inpatient ward to the clinic. The pharmacists' primary task was to perform medication reconciliation and to identify and resolve DTPs. The pharmacists also provided medication education to patients and pharmacy consultations to clinic staff. Working with the outpatient pharmacy, the pharmacists helped to clarify prescriptions and drug coverage issues. Medication discrepancies identified and interventions performed by the pharmacists were recorded and were later graded for clinical significance by a panel of clinicians. Patient and staff satisfaction surveys were conducted at random during the study period. Barriers to the flow of patient care and other operational issues were documented. RESULTS: The 2 pharmacists saw a total of 35 patients over 100 visits. They identified a total of 50 medication discrepancies involving 17 (49%) of the patients and 70 DTPs involving 23 (66%) of the patients. Thirty-one of the 70 DTPs resulted directly from a medication discrepancy. Twenty (95%) of the 21 unintentional medication discrepancies and 7 (70%) of the 10 undocumented intentional medication discrepancies were graded as clinically significant or moderately significant. Satisfaction surveys completed by patients and clinic staff yielded positive responses supporting pharmacists' participation. CONCLUSIONS: Pharmacists working as part of the multidisciplinary team identified and resolved medication discrepancies, thereby improving medication safety at the allo-HCT clinic.

CONTEXTE: Les patients subissant une greffe allogénique de cellules souches hématopoïétiques (GACSH), appuyée par un traitement médicamenteux complexe, sont vulnérables aux problèmes pharmacothérapeutiques lors de changement de milieu de soins après avoir reçu leur congé de l'hôpital et pourraient tirer profit d'interventions et de conseils pharmaceutiques en temps opportun. OBJECTIF: Déterminer les répercussions sur la sécurité des médicaments de la participation d'un pharmacien et les obstacles potentiels à sa participation à l'équipe multidisciplinaire d'une unité clinique de GACSH. MÉTHODES: Deux pharmaciens se sont relayés pour se joindre à l'équipe de l'unité clinique de GACSH d'un centre de cancérologie tertiaire affilié à une université, entre janvier et juin 2010 (participation à une des trois journées par semaine d'ouverture de l'unité clinique). Pour chaque patient qu'il a rencontré, le pharmacien a comparé les médicaments prescrits au départ de l'hôpital au schéma pharmacothérapeutique adopté à l'unité de GACSH. La principale tâche des pharmaciens était d'effectuer un bilan comparatif des médicaments et de détecter et de résoudre tout problème pharmacothérapeutique. Les pharmaciens devaient également fournir des conseils sur les médicaments aux patients et des consultations au personnel de l'unité clinique. En collaboration avec la pharmacie externe, le pharmacien aidait à clarifier les ordonnances et à préciser les modalités de remboursement des médicaments. Les divergences médicamenteuses relevées par les pharmaciens et les interventions effectuées par ceux-ci ont été consignées, puis dans un second temps classées par un panel de cliniciens selon leur importance clinique. Des sondages sur la satisfaction des patients et du personnel ont été effectués au hasard pendant la période de l'étude. Les obstacles au bon déroulement des soins aux patients et d'autres problèmes de fonctionnement ont été cernés et consignés. RÉSULTATS: Les deux pharmaciens ont vu 35 patients en tout au cours de 100 visites. Ils ont détecté un total de 50 divergences médicamenteuses touchant 17 (49 %) des patients et 70 problèmes pharmacothérapeutiques touchant 23 (66%) des patients. Trente-et-un de ces 70 problèmes pharmacothérapeutiques étaient directement attribuables à une divergence médicamenteuse. Vingt (95 %) des 21 divergences non intentionnelles et 7 (70 %) des 10 divergences intentionnelles non consignées ont été classées comme étant significatives ou modérément significatives sur le plan clinique. Les sondages sur la satisfaction remplis par les patients et le personnel de l'unité ont dégagé des réponses favorables à la participation des pharmaciens. CONCLUSIONS: Les pharmaciens qui ont participé à l'équipe multidisciplinaire ont détecté et résolu des divergences médicamenteuses, améliorant ainsi la sécurité des médicaments à l'unité de GACSH. [Traduction par l'éditeur].

Safety and efficacy of CHOP for treatment of diffuse large B-cell lymphoma with different combination antiretroviral therapy regimens: SCULPT study.

BACKGROUND: Use of combination antiretroviral therapy (cART) and cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) with or without rituximab for treatment of diffuse large B-cell lymphoma (DLBCL) in HIV substantially increases response rates but may also increase toxicity, possibly due to antiretroviral-antineoplastic drug interactions. The objective of this study was to evaluate the frequency of complete remission (CR) of DLBCL in patients treated with CHOP while receiving a protease inhibitor (PI) versus a non-PI-based cART. METHODS: A retrospective multicentre pilot study was conducted in HIV-infected patients on cART treated for DLBCL with CHOP between 2002-2010 in three academic hospitals. RESULTS: A total of 34 patients were included with 65% and 35% of patients receiving a PI and non-PI-based cART, respectively. Baseline characteristics between groups were similar; overall 85% were male, median age was 43 years, 50% had an International Prognostic Index (IPI) of 2-3 and median CD4(+) T-cell count was 225 cells/mm(3). CR was achieved in 77% and 58% of patients in the PI and non-PI groups, respectively (P=0.21), with 65% and 63% of patients achieving 2-year overall survival (P=1.00). A multivariate analysis showed that lower IPI score alone was significantly associated with higher CR rates (P=0.05). Toxicity was similar between both groups. CONCLUSIONS: Similar efficacy and toxicity of CHOP was observed in patients receiving a PI and non-PI-based cART.

Acute renal failure, gastrointestinal bleeding, and cardiac arrhythmia after administration of arsenic trioxide for acute promyelocytic leukemia.

PURPOSE: The case of a patient who developed acute renal failure, gastrointestinal bleeding, and cardiac arrhythmia after receiving arsenic trioxide for the treatment of acute promyelocytic leukemia (APL) is described. SUMMARY: An 84-year-old Caucasian woman with a history of osteoarthritis sought medical attention for relapse of her APL, which had initially been diagnosed approximately 30 months earlier. Complete remission was accomplished with three cycles of i.v. daunorubicin for 3 days and oral tretinoin for 28 days. After 19 months in remission, she was noted to have increased bruising and blood test values consistent with APL relapse. Two additional trials of oral tretinoin were unsuccessful, and arsenic trioxide was initiated at a daily dosage of 0.15 mg/kg of actual body weight. Less than 24 hours after receiving arsenic trioxide, the patient had "bile-like emesis" and her hemoglobin level decreased. Upper gastrointestinal bleeding was suspected and managed aggressively with transfusions of platelets and fresh frozen plasma and i.v. desmopressin. She became anuric, and her serum creatinine level more than doubled. Hemodialysis was started due to a sudden increase in potassium and fluid overload that did not respond to i.v. furosemide. One hour after hemodialysis, the patient was found pulseless and unresponsive by nursing staff. The cardiac arrest team rapidly responded and noted atrial fibrillation with a fast ventricular rate. Postresuscitation, the patient was transferred to the intensive care unit. Despite aggressive life-support therapy, the patient remained unresponsive. CONCLUSION: An 84-year-old woman developed acute renal failure, gastrointestinal bleeding, and cardiac arrhythmia after receiving arsenic trioxide for the treatment of APL.

CNS relapses of acute promyelocytic leukemia after all-trans retinoic acid.

OBJECTIVE: To review the role of all-trans retinoic acid (ATRA) and arsenic trioxide in central nervous system (CNS) relapses of acute promyelocytic leukemia (APL). CASE SUMMARY: A 69-year-old white man diagnosed with APL presented with bleeding diathesis. His molecular and cytogenetic studies were positive for promyelocytic leukemia-retinoic acid receptoralpha (PML-RARalpha) and t(15;17) transformation. Complete molecular and cytogenetic remission was achieved with ATRA, daunorubicin, and cytarabine. Within 6 months, the patient was readmitted for investigation of severe global headaches and an ataxic gait. His peripheral blood and cerebral spinal fluid were positive for PML-RARalpha fusion protein. Intrathecal chemotherapy and radiation, as well as ATRA, were the main treatment modalities provided. Molecular and cytogenetic remission was again obtained. Three months later, a second relapse occurred in the CNS and the peripheral blood. DISCUSSION: APL is typically treated with anthacycline-based chemotherapy and ATRA. Approximately 85-95% of patients achieve complete remission (CR); however, the relapse rate has been reported to be about 30-40%. A thorough literature search (MEDLINE, EMBASE, CANCERLIT, 1966-January 2002) revealed only 54 cases of extramedullary disease, of which 35 involved the CNS. CONCLUSIONS: The introduction of ATRA has improved patient survival dramatically. APL relapse, in general, has been in part attributable to repetitive or prolonged exposure to ATRA and the possibility of additional chromosomal changes, making the disease more refractory to treat. Given the evidence, one could argue that, with repeated ATRA treatment, CR duration may be shortened. However, limited data are available to guide the appropriate management of APL relapsed to the CNS with either ATRA, chemotherapy, or arsenic trioxide. In our opinion, treatment using arsenic trioxide is an unconventional option worthy of exploring.

Acute tumor lysis syndrome secondary to hydroxyurea in acute myeloid leukemia.

OBJECTIVE: To report 2 cases of acute tumor lysis syndrome (ATLS) associated with hydroxyurea treatment. CASE SUMMARY: A 79-year-old woman diagnosed with chronic lymphocytic leukemia presented with an acute blastic transformation. She was promptly hydrated, started on allopurinol, and treated with hydroxyurea. About 24 hours later, her biochemistry panel showed parameters consistent with ATLS when compared with pretreatment levels. The second case was a 76-year-old man newly diagnosed with acute myeloid leukemia presenting with high blast fraction. He was given appropriate hydration and allopurinol prophylaxis, and was started on high-dose hydroxyurea treatment. He became symptomatic after 12 hours and results of his blood work were consistent with ATLS. DISCUSSION: ATLS is a well-known metabolic disturbance that occurs after cell destruction of rapidly growing tumors. In standard doses, hydroxyurea leads to cell death in the S phase and is not thought to cause significant cell lysis. However, in large doses, it possibly acts by a different mechanism and had a direct cytolytic effect associated with ATLS in our patients. CONCLUSIONS: Although ATLS caused by hydroxyurea appears to be rare, patients at risk should be closely monitored for this complication. An objective causality assessment using the Naranjo probability scale revealed that the adverse drug reaction was probable between ATLS and hydroxyurea therapy in these 2 patients.