scholarly journals ECIL guidelines for the diagnosis of Pneumocystis jirovecii pneumonia in patients with haematological malignancies and stem cell transplant recipients

2016 ◽  
Vol 71 (9) ◽  
pp. 2386-2396 ◽  
Author(s):  
Alexandre Alanio ◽  
Philippe M. Hauser ◽  
Katrien Lagrou ◽  
Willem J. G. Melchers ◽  
Jannik Helweg-Larsen ◽  
...  
Keyword(s):  
Fungal Infections ◽  
Pneumocystis Jirovecii ◽  
High Dose ◽  
Pneumocystis Jirovecii Pneumonia ◽  
Cell Transplant ◽  
Haematological Malignancies ◽  
Early Management ◽  
Non Invasive ◽  
Patient At Risk

AbstractThe Fifth European Conference on Infections in Leukaemia (ECIL-5) convened a meeting to establish evidence-based recommendations for using tests to diagnose Pneumocystis jirovecii pneumonia (PCP) in adult patients with haematological malignancies. Immunofluorescence assays are recommended as the most sensitive microscopic method (recommendation A-II). Real-time PCR is recommended for the routine diagnosis of PCP (A-II). Bronchoalveolar lavage (BAL) fluid is recommended as the best specimen as it yields good negative predictive value (A-II). Non-invasive specimens can be suitable alternatives (B-II), acknowledging that PCP cannot be ruled out in case of a negative PCR result (A-II). Detecting β-d-glucan in serum can contribute to the diagnosis but not the follow-up of PCP (A-II). A negative serum β-d-glucan result can exclude PCP in a patient at risk (A-II), whereas a positive test result may indicate other fungal infections. Genotyping using multilocus sequence markers can be used to investigate suspected outbreaks (A-II). The routine detection of dihydropteroate synthase mutations in cases of treatment failure is not recommended (B-II) since these mutations do not affect response to high-dose co-trimoxazole. The clinical utility of these diagnostic tests for the early management of PCP should be further assessed in prospective, randomized interventional studies.

scholarly journals 36. Evaluation of a Best Practice Alert (BPA) to Improve Pneumocystis jirovecii Prophylaxis Prescribing in Cancer Patients Receiving High-dose Corticosteroids in an Outpatient Setting

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S140-S140
Author(s):  
Justine Abella Ross ◽  
Bernard Tegtmeier ◽  
Deron Johnson ◽  
Deepa Nanayakkara ◽  
Alfredo Puing ◽  
...  
Keyword(s):  
Best Practice ◽  
Fluorescent Antibody ◽  
Immunosuppressive Drugs ◽  
Outpatient Setting ◽  
Pneumocystis Jirovecii ◽  
High Dose ◽  
Pneumocystis Jirovecii Pneumonia ◽  
Cell Transplant ◽  
Post Intervention ◽  
Best Practice Alert

Abstract Background In patients (pts) with cancer, the risk of Pneumocystis jirovecii pneumonia (PJP) is a function of dose and duration of corticosteroids (CS), underlying immunodeficiency, and immunosuppressive drugs. Trimethoprim/sulfamethoxazole (TMP/SMX) and atovaquone (ATO) are effective prophylaxis (ppx) agents against PJP. Guidelines recommend PJP ppx for pts on > 20 mg /day of prednisone or its equivalent for ≥ 1 month. A best practice alert (BPA) to identify pts receiving CS may assist with improving PJP ppx prescribing in cancer pts. Methods PJP BPA was created to identify pts on CS (excluding hydrocortisone) with no active prescription for TMP/SMX or ATO ppx in EMR. Dapsone and pentamidine excluded since not preferred agents at our institution. PJP case: positive PJP polymerase chain reaction (PCR) from bronchoalveolar lavage (BAL) > 84 copies or positive PJP direct fluorescent antibody (DFA) or cytology with clinical and radiographic suspicion. PJP PCR from BAL < 84 copies/ml with negative DFA and cytology excluded. Preventable PJP (P-PJP): pts after CS > = 30 days without PJP ppx. Non-preventable PJP (NP-PJP) : pts after CS < 30 consecutive days, or on PJP ppx (non-compliance, failure), or day +1 to +30 post hematopoietic cell transplant (HCT). Pre-intervention (pre-i) PJP pts 3/1/2018 to 7/31/19 (17 months), post-intervention (post-i) PJP pts 8/1/19 to 2/1/20 (18 months) evaluated to assess BPA impact on PJP inpatient (inpt) admissions. Results In the post-i, the BPA fired 3,588 times in 1,302 pts. Pre-i: 20 P-PJP, 13 NP-PJP out of 33 pts. Post-i: 6 P-PJP, 25 NP-PJP out of 31 pts. The BPA fired in 4/31 PJP pts in the post-i period: 2/6 of P-PJP, 2/25 NP-PJP. The number of P-PJP decreased from 20 to 6 in the post-i period (p=0.0097). Conclusion Implementation of a decision support tool significantly decreased the number of P-PJP. The BPA was limited by identifying pts after CS were prescribed after the initial visit leading to periods of CS use without ppx and inability to calculate CS dosing and length of prescription. BPA provided passive education in the outpatient setting and future opportunities include refining the EMR to better identify pts at risk for developing PJP. Disclosures All Authors: No reported disclosures

scholarly journals Pneumocystis jirovecii pneumonia: still a concern in patients with haematological malignancies and stem cell transplant recipients

2016 ◽  
Vol 71 (9) ◽  
pp. 2379-2385 ◽  
Author(s):  
Catherine Cordonnier ◽  
Simone Cesaro ◽  
Georg Maschmeyer ◽  
Hermann Einsele ◽  
J. Peter Donnelly ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplant ◽  
Laboratory Diagnosis ◽  
Pneumocystis Jirovecii ◽  
Pneumocystis Jirovecii Pneumonia ◽  
Cell Transplant ◽  
Haematological Malignancies ◽  
Transplant Recipients ◽  
Allogeneic Hsct ◽  
Prevention And Treatment

The risk of patients with ALL and recipients of an allogeneic HSCT developing Pneumocystis jirovecii pneumonia is sufficiently high to warrant guidelines for the laboratory diagnosis, prevention and treatment of the disease. In this issue, the European Conference on Infections in Leukemia (ECIL) presents its recommendations in three companion papers.

scholarly journals 837. Performance of Blood (1- >3)-β-D-Glucan in People with AIDS Presenting with Respiratory Symptoms

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S510-S511
Author(s):  
Lana Hasan ◽  
Gayathri Krishnan ◽  
Michael Saccente
Keyword(s):  
Bronchoalveolar Lavage ◽  
Diagnostic Test ◽  
Test Performance ◽  
Respiratory Symptoms ◽  
Fungal Infections ◽  
Pneumocystis Jirovecii ◽  
Cape Cod ◽  
Pneumocystis Jirovecii Pneumonia ◽  
Non Invasive ◽  
Progressive Disseminated Histoplasmosis

Abstract Background The gold standard for diagnosis of Pneumocystis jirovecii pneumonia (PCP) is direct visualization of the microorganism in respiratory samples, usually obtained via bronchoalveolar lavage (BAL). Blood β-D-glucan (BDG) is used as a non-invasive adjunctive diagnostic test for PCP, but specificity is only modest, in part because other opportunistic fungal infections cause high BDG. We previously showed BDG-positivity in 94% of people with AIDS (PWA), progressive disseminated histoplasmosis (PDH), and respiratory symptoms in our hospital. In this study, we aim to assess the performance of BDG as a diagnostic test for PCP in PWA who have respiratory symptoms. Methods We retrospectively identified PWA who had a BDG result between 2014 and 2019. AIDS was defined as past or current absolute CD4 count < 200 cells/µL, or a past or current AIDS-defining condition. Positive cytological or histological evidence of P. jirovecii in bronchoalveolar lavage (BAL) fluid or lung biopsy, or positive Pneumocystis PCR on sputum or BAL confirmed PCP. The Fungitell Assay (Associates of Cape Cod, East Falmouth, MA) determined BDG levels as follows: negative, < 60 pg/mL; indeterminate, 60-79 pg/mL, and positive, ≥ 80 pg/mL. Values < 31 pg/mL and those >500 pg/mL were censored at 30 pg/mL and 500 pg/mL, respectively. Respiratory symptoms were defined as cough, dyspnea, chest pain, or hypoxia. We compared BDG results for participants with proven PCP and participants without proven PCP. Results We identified 260 PWA with a BDG result, of whom 183 had at least one respiratory symptom. 84 (45.9%) of these participants had a positive BDG. BDG results among participants with and without PCP are shown in Table 1. Of the 44 participants with a positive BDG who did not have PCP, 29 (65.9%) had PDH. Other diagnoses included cryptococcosis and candidemia. The test performance of BDG for the diagnosis of PCP is shown in Table 2. Exclusion of participants with PDH increased the specificity of BDG for PCP to 86.4%. Table 1. Results of (1->3)-β-D-glucan Testing by Pneumocystis jirovecii Pneumonia Diagnosis Among Participants with AIDS and Respiratory Symptoms Table 2. Test Performance of (1->3)-β-D-glucan for the Diagnosis of Pneumocystis jirovecii Pneumonia* Conclusion At our center where histoplasmosis is endemic, a positive BDG should not be attributed to PCP among PWA with respiratory symptoms because of low specificity and low positive predictive value. However, a negative BDG can exclude PCP in this population. Disclosures All Authors: No reported disclosures

Holmium-166 (166Ho)-DOTMP Skeletal Targeted Radiotherapy (STR™) with Melphalan and Autologous Peripheral Stem Cell Transplant (PBSCT) for Multiple Myeloma (MM).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 922-922 ◽  
Author(s):  
Mark Goodman ◽  
William I. Bensinger ◽  
Sergio Giralt ◽  
Donna Salzman ◽  
Katherine L. Ruffner ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Hemorrhagic Cystitis ◽  
Conditioning Regimen ◽  
Complete Response ◽  
Phase Iii ◽  
High Dose ◽  
Cell Transplant ◽  
Red Marrow

Abstract Background: 166Ho-DOTMP is a beta-emitting radiophosphonate that localizes specifically to the bone surfaces and can deliver high dose radiation both to the bone and bone marrow. Follow-up data from 3 clinical trials with STR as conditioning for patients with MM undergoing autologous PBSCT are presented. Methods: In 2 Phase I/II dose-escalation trials, 83 patients received a dose of 166Ho-DOTMP STR calculated to deliver 20, 30, or 40 Gy to the red marrow; 82 pts received melphalan (140 or 200 mg/m2) ± 8 Gy TBI (n=25), followed by PBSCT. As of June, 2004, 77 subjects have been followed for at least 48 months. In a separate Phase II dosimetry trial, 12 patients received two 30 mCi tracer doses of 166Ho-DOTMP STR to determine the reproducibility of biodistribution and pharmacokinetics (PK). All pts received a 25 Gy therapy dose with concurrent IV hydration and continuous bladder irrigation, followed by 200 mg/m2 melphalan and PBSCT. These patients have been followed for at least 18 months. Results: Up to 2.3 Ci/m2, 166Ho-DOTMP STR was given in the Phase I/II trials; 29/83 (35%) patients achieved complete response (CR) and overall response rate (CR + PR) was 64% (7 pts not evaluable). The Kaplan-Meier estimate of median survival is 5.2 years for all 83 patients. In patients who are at least 4 years post transplant who achieved a CR, the survival is 74% (n=27). In patients who achieved less than a CR at least 4 years ago, the survival is 34% (n=44). Dose-related radiation-induced kidney toxicity presented in some patients more than 6 months post-therapy. The dose of 166Ho-DOTMP STR in the Phase II dosimetry trial was 550 to 860 mCi/m2, 166Ho-DOTMP. Currently, 18 months of follow-up reveals no occurrence of hemorrhagic cystitis or > Grade 2 elevated creatinine. A CR rate of 17% with an overall survival of 92%, was observed. In 10 patients who received 166Ho-DOTMP STR 750 mCi/m2 ± 10% in the Phase I/II trial, the CR rate was 40%, and the 4-year survival was 70%. Monitoring for safety and duration of response is ongoing in all 3 trials. Conclusion: Follow-up from the Phase I/II trials confirms that 166Ho-DOTMP STR provides favorable efficacy and safety as part of the conditioning regimen for patients with MM undergoing PBSCT. A Phase III, randomized multicenter study is now open to enrollment, comparing the safety and efficacy of 166Ho-DOTMP STR plus melphalan to melphalan alone as conditioning for PBSCT in subjects with primary refractory MM who have failed to respond to induction therapy, including high-dose dexamethasone, and are within 18 months of diagnosis.

GM-CSF in Stem Cell Transplant (SCT) Recipients: Impact of Graft-Versus Host Disease on Invasive Fungal Infections (IFIs)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4367-4367
Author(s):  
Amar Safdar ◽  
Gilhen Rodriguez ◽  
Georgina Georgescu ◽  
Richard Champlin
Keyword(s):  
Fungal Infections ◽  
Underlying Disease ◽  
P Value ◽  
High Dose ◽  
Cell Transplant ◽  
Retrospective Case ◽  
Graft Versus Host ◽  
Gm Csf ◽  
Younger Age ◽  
The Impact

Abstract Background: GM-CSF is thought to be beneficial in SCT patients with IFI. The impact of GM-CSF in SCT recipients with GVHD and IFI was evaluated Methods: A retrospective case-matched (GM-CSF [n = 12] vs. no GM-CSF [n = 27]) study was undertaken to compare outcomes if IFIs diagnosed >100 days following transplantation during 2000–2006. A response was defined as complete or partial response (CR/PR) and considered 3 months after IFI diagnosis or earlier in patients with earlier response. All value are given as median ± s.d. The systemic antifungal therapy in > 60% of patients included echinocandin and anti-mold triazole, or polyene agent. Results: Please refer to the table below. Patients who received GM-CSF were younger (age 36 ± 17 vs. 51 ± 13 years); neutropenic (<500 cells/uL) at onset of infection (50% vs. 11%; P = 0.014); had lower monocyte counts (10 ± 236 vs. 220 ± 575 cells/uL; P = 0.021) and frequently required intensive care unit stay (50% vs 15%; P = 0.043). A 50% response was observed in the GM-CSF treated SCT recipients with GVHD and IFIs, whereas, 41% response occurred in the group who received no concurrent Gm-CSF (P = 0.6). Similarly, IFI-associated deaths were less frequently observed in GM-CSF treated patients (41%) compared with 55% seen in patients who had not received GM-CSF (P = 0.7). There was a slight increase in survival among SCT recipients treated with GM-CSF (48 ± 21 days vs. 34 ± 19 days in no GM-CSF group P = 0.05) Conclusions: Late fungal infections in SCT recipients with GVHD, when treated with GM-CSF-based therapy had comparable outcomes despite having significantly more neutropenia, severe monocytopenia and ICU stay. Characteristics GM-CSF N = 12 (5% No GM-CSF N = 27 (%) p-value Underlying Disease-Leukemia Relapsed/refractory Cancer 10 (83) 5 (42) 18 (67) 6 (22) 0.12 0.26 Proven and probable IFI 9 (75) 21 (78) 1 GVHD (extensive) 5 (42) 14 (52) 0.57 High Dose Steroids 7 (58) 18 (67) 0.72 Disseminated IFI 3 (25) 4 (15) 0.65 Breakthrough IFI 10 (83) 25 (93) 0.57 APACHI II Score at time of IFI diagnosis 11+/−4 (range 5–18) 12+/−3 (range 5–19) 0.47

Characteristics and Outcome of Patients with Acute Myeloid Leukemia (AML) Refractory to One Cycle of High Dose Cytarabine-Based Induction Chemotherapy.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1038-1038
Author(s):  
Farhad Ravandi ◽  
Jorge Cortes ◽  
Stefan Faderl ◽  
Susan O'Brien ◽  
Guillermo Garcia-Manero ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplant ◽  
Conflicts Of Interest ◽  
Single Agent ◽  
Salvage Chemotherapy ◽  
High Dose ◽  
Cell Transplant ◽  
Refractory Disease ◽  
Allogeneic Stem Cell Transplant

Abstract Abstract 1038 Poster Board I-60 Background: Outcome of patients (pts) with AML refractory to initial induction is assumed to be poor but the available data is limited. Furthermore, pts refractory to standard dose cytarabine-based regimens may be salvaged with high dose ara-C (HiDaC, defined as daily ara-C dose ≥ 1 g/m2). Information on the outcome of pts refractory to initial HiDaC - based induction is more limited. Aim To better characterize predictors of poor response to HiDaC-based induction and to evaluate the outcome of pts refractory to such induction regimens. Methods: We identified pts treated with induction regimens containing HiDaC at the University of Texas – M D Anderson Cancer Center who did not achieve a compete remission (CR) after one cycle of induction. We examined their pre-treatment characteristics and compared them with similar pts achieving a CR. We also examined their response to salvage chemotherapy and outcome. Results: Among 1179 pts treated with HiDaC-based induction therapy from 1995 to 2009, 285 were primary refractory to one course of induction. Their median age was 59 (range, 18 - 85). Median pretreatment WBC was 9.0 × 109/L (range, 0.3 – 394 × 109/L). Cytogenetics included-5/-7/complex 101 (35%), diploid 85 (30%), other intermediate 98 (34%), favorable 1 (<1%). 165 (58%) pts had antecedent hematological disorder. Induction regimens used included HiDaC with anthracyclines (n=181, 64%), HiDaC with non-anthracycline chemotherapy (fludarabine, clofarabine, topotecan, and troxacitabine) (n=104, 36%) Pts with primary refractory disease were older (Median age 59 vs. 56; p=000004), more likely to have chromosome 5/7 or complex cytogenetic abnormalities (P=0.0001), more likely to have AHD (p=0.0001), and had a higher presentation WBC (P=0.036), but not a higher incidence of FLT3 mutations (p=0.85) than those achieving CR. Primary refractory disease was not more likely with non-anthracycline containing regimens than those with anthracyclines (p=0.58). Salvage chemotherapy included combination chemotherapy in 111 (39%)(non-ara-C regimen in 40, containing ara-C in 71), single agent chemotherapy in 64 (22%), allogeneic stem cell transplant in 22 (8%) and none in 88 (31%). Forty-three (15%) pts responded to salvage including 35 CR and 8 CRp. 114 (58%) pts were resistant and 35 (18%) died; 5 (3%) were lost to follow-up. With a median follow-up of 115 weeks (range 8 – 347 weeks) in pts responding to salvage, 21 pts (7%) were alive and in CR, for at least 6 months including 14 who underwent an allogeneic stem cell transplant (median overall survival for these 21 pts, 30 months; range, 13 to 87 months). Conclusions: Outcome of pts with disease refractory to HiDaC-based induction is poor. Alternative strategies are needed in these pts who are likely to be resistant to standard chemotherapy. Disclosures: No relevant conflicts of interest to declare.

A Detailed Evaluation of Transplant-Related Toxicities and Outcome for Patients with CNS Lymphoma (CNSL) Consolidated with High-Dose Therapy and Autologous Stem Cell Transplantation (HDT-ASCT) Using Thiotepa, Busulfan (Bu), Cyclophosphamide (TBC) Conditioning

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4354-4354
Author(s):  
Michael Scordo ◽  
Valkal Bhatt ◽  
Meier Hsu ◽  
Antonio M. Omuro ◽  
Matthew J. Matasar ◽  
...  
Keyword(s):  
Research Funding ◽  
Secondary Malignancy ◽  
Cns Lymphoma ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Cell Transplant ◽  
Kaplan Meier ◽  
Clinically Significant ◽  
Grade 3

Abstract Background: HDT-ASCT with TBC conditioning has emerged as a common consolidation strategy for patients (pts) with relapsed/refractory (rel/ref) primary (PCNSL) or secondary (SCNSL) (Welch et al, Leuk & Lymph 2014). In a prospective study, chemosensitive PCNSL pts in first remission after induction with R-MPV (rituximab, MTX, procarbazine and vincristine) proceeding to HDT-ASCT with TBC conditioning, experienced an encouraging 2-year PFS and OS of 75% and 81%, respectively (Omuro et al, Blood, 2015). Three of these patients experienced transplant-related mortality (TRM, 11.5%), which appears greater than HDT-ASCT for other lymphomas. The purpose of this report is to correlate characteristic toxicities of TBC conditioning for CNSL to pre-HDT-ASCT clinical variables. Methods: The MSKCC IRB approved this retrospective chart review. Eligible pts (n=34) were ≥ 18 years of age with PCNSL or SCNSL that was chemosensitive to induction therapy after which they proceeded to HDT-ASCT conditioned with TBC between December 2006 and April 2015. All pts included were treated outside of prospective clinical trials. Clinically significant grade 3-5 non-hematologic toxicities per CTCAE 4.0 occurring in >20% of pts were recorded from the initiation of conditioning until 6 months post ASCT (Figure 1). Pre-HDT-ASCT variables for analysis include: age, gender, disease (PCNSL or SCNSL), Karnofsky performance status (KPS), hematopoietic cell transplant comorbidity index (HCT-CI), number of prior regimens, prior use of whole-brain radiotherapy (WBRT), and disease status prior to HDT-ASCT (CR/CRu or PR). We evaluated the association of these pre-HDT-ASCT characteristics with the number of clinically significant grade 3-5 non-hematologic toxicities (≥4 vs. <4) using FisherÕs exact test. We further estimated progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier methods. Results: Thirty-three patients (97%) experienced ≥ 1 grade 3-5 non-hematologic toxicity. Febrile neutropenia (grade 3) occurred in 32 pts (94%). Of all pre-HDT-ASCT variables, only the number of prior regimens (>2) was significantly associated with incurring more grade 3-5 non-hematologic toxicities, p=0.04 (Table 1). With a median follow-up for survivors of 12 months (range, 1.5-86.2 months), PFS was 79% (95% CI, 65-96) and OS was 82% (95% CI, 68-98) at 1 year (Figures 2 and 3). During the follow-up period, there were 7 pt deaths: 4 died of disease, 2 died secondary to TRM (5.9%), and one died of a secondary malignancy (squamous cell carcinoma) 86.2 months after HDT-ASCT. There were no progression events beyond 12 months. In a limited subset analysis wherein n=22 had first dose bu pharmacokinetics evaluated, pre-HDT-ASCT variables were not associated with higher bu AUC levels, though 64% of these pts required a dose reduction. Conclusions: We reaffirmed that HDT-ASCT with TBC conditioning is effective consolidation for CNSL, but it is associated with more grade 3-5 non-hematologic toxicity in pts having had >2 prior regimens. Risk-adapted dose attenuation of TBC conditioning for this group of pts may mitigate observed toxicity. Table 1. Association of Pre-ASCT Variables & Grade 3-5 Non-hematologic Toxicities Number of Clinically Significant Grade 3-5 Toxicities Pre-ASCT Variables All (N=34) Fewer than 4 (N=21) 4 or more (N=13) p-value Age 0.71 <60 23 (68%) 15 (71%) 8 (62%) ≥60 11 (32%) 6 (29%) 5 (38%) Gender 0.72 Female 13 (38%) 9 (43%) 4 (31%) Male 21 (62%) 12 (57%) 9 (69%) Disease 0.30 PCNSL 19 (56%) 10 (48%) 9 (69%) SCNSL 15 (44%) 11 (52%) 4 (31%) KPS 0.99 ≥80 32 (94%) 20 (95%) 12 (92%) <80 2 (6%) 1 (5%) 1 (8%) BMT HCT CI 0.99 ≤2 17 (50%) 11 (52%) 6 (46%) >2 17 (50%) 10 (48%) 7 (54%) Number of Prior Regimens 0.04 ≤2 21 (62%) 16 (76%) 5 (38%) >2 13 (38%) 5 (24%) 8 (62%) WBRT 0.17 No 28 (82%) 19 (90%) 9 (69%) Yes 6 (18%) 2 (10%) 4 (31%) Disease state prior 0.99 CR/CRu 29 (85%) 18 (86%) 11 (85%) PR 5 (15%) 3 (14%) 2 (15%) Figure 1. Analysis of Grade 3-5 Non-Hematologic Toxicities Figure 1. Analysis of Grade 3-5 Non-Hematologic Toxicities Figure 2. Kaplan-Meier Curve for PFS Figure 2. Kaplan-Meier Curve for PFS Figure 3. Kaplan-Meier Curve for OS Figure 3. Kaplan-Meier Curve for OS Disclosures Bhatt: Spectrum: Consultancy. Moskowitz:GSK: Research Funding; Merck: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding. Giralt:TAKEDA: Consultancy, Honoraria, Research Funding; JAZZ: Consultancy, Honoraria, Research Funding, Speakers Bureau; AMGEN: Consultancy, Research Funding; SANOFI: Consultancy, Honoraria, Research Funding; CELGENE: Consultancy, Honoraria, Research Funding.

Rituximab, methotrexate (MTX), procarbazine, and vincristine (R-MPV) followed by consolidation high-dose chemotherapy (HDC) and autologous stem-cell transplant (ASCT) for newly diagnosed primary CNS lymphoma (PCNSL).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2008-2008 ◽  
Author(s):  
Antonio Marcilio Padula Omuro ◽  
Denise Correa ◽  
Craig Moskowitz ◽  
Matthew J. Matasar ◽  
Lisa Marie DeAngelis ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Primary Endpoint ◽  
Primary Cns Lymphoma ◽  
Unknown Etiology ◽  
Cns Lymphoma ◽  
High Dose ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Induction Regimen

2008 Background: In our previous study in newly diagnosed PCNSL, induction chemotherapy with MTX and cytarabine followed by consolidation HDC (carmustine, etoposide, cytarabine, melphalan [BEAM]) with ASCT without radiotherapy resulted in only 50% of pts transplanted, reflecting low efficacy of induction chemotherapy, and short intent-to-treat (ITT) median PFS (=6m). In this phase II trial, we sought to optimize this strategy by utilizing a more effective induction regimen (R-MPV) and a more aggressive HDC regimen (Soussain et al). Methods: Pts received 5-7 cycles of R-MPV (MTX: 3.5g/m2) and if a partial or complete response was achieved, HDC with thiothepa, cyclophosphamide and busulfan was given, followed by ASCT and no radiotherapy. The primary endpoint was ITT 1 year event-free survival (promising: 75%, non-promising: 50%; 90% power, significance=0.05). Follow-up included comprehensive neuropsychological evaluation. Results: Accrual has been completed (N=32 pts, median age 57 [range 23-67], median KPS=80). Following R-MPV, 17 pts achieved a CR, 13 pts a PR and two pts progressed. A total of 25 (78%) pts were transplanted; the reasons for not receiving transplant were progressive disease (N=2), poor performance status/ physician’s decision (N= 2), mobilization failure (N=1) and consent withdrawn (N= 2). One pt who withdrew consent relapsed and received HDCASCT for salvage. Two (8%) pts died from early complications of ASCT (Stevens-Johnson: one, sepsis: one) and one pt experienced a fatal late colitis of unknown etiology. In the ITT population, the median EFS and OS have not been reached after a median follow-up of 22 months. The 1 year EFS was 78% (95%CI 58-90) and the 2y OS was 76% (95% CI 54-89). No pt has developed delayed neurotoxicity. Conclusions: R-MPV induction regimen resulted in improved response rates, allowing 78% of pts to receive HDC-ASCT. Although more toxic, this regimen resulted in excellent disease control and survival in the ITT population, far exceeding the efficacy of our previous transplant study. The primary endpoint was met, warranting further investigation.

Improving the care of acute lymphocytic leukemia (ALL) at a large county hospital.

2013 ◽  
Vol 31 (31_suppl) ◽  
pp. 213-213 ◽  
Author(s):  
Meghan Sri Karuturi ◽  
Jeffrey Thomas Yorio ◽  
Annie Titus ◽  
Stephenie Jeanette Pharr ◽  
Alyssa G. Rieber
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Biopsy ◽  
Underserved Populations ◽  
Philadelphia Chromosome ◽  
The United States ◽  
Lymphocytic Leukemia ◽  
High Dose ◽  
Cell Transplant ◽  
Newly Diagnosed

213 Background: The treatment of ALL involves complex chemotherapy regimens that are difficult to deliver to underserved populations. Lyndon B. Johnson General Hospital (LBJGH) provides care to uninsured and underinsured patients in Harris County, the third largest county in the United States. Our goal is to achieve 80% adherence to National Comprehensive Cancer Network guidelines in the care of newly diagnosed ALL patients at LBJGH. Methods: The charts of 14 patients with newly diagnosed ALL were reviewed. Demographics, initial work-up (e.g., bone marrow biopsy and aspirate), type of treatment, adherence to scheduled treatment, use of supportive medications, outpatient follow-up, stem cell transplant referral and quality of provider documentation were collected. Areas of potential improvement were then identified using provider focus groups and Ishikowa Diagram. The project was approved by the MD Anderson Quality Improvement Assessment Board. Results: 12/14 patients were evaluable, having received their full course of care at LBJGH. The median age was 35, 9/12 (75%) were female and 9/12 (75%) were Hispanic. 6/11 (55%) cases expressed CD20 (CD20+) and 3/11 (27%) were Philadelphia chromosome positive (Ph+). All 12 patients received induction and consolidation therapy with the HyperCVAD regimen (cyclophosphamide/vincristine/doxorubicin/dexamethasone alternating with high-dose methotrexate/cytarabine). Bone marrow biopsy at time of diagnosis, use of a tyrosine kinase inhibitor for Ph+ ALL, and use of supportive medications occurred >80% of the time. Administration of outpatient chemotherapy, use of rituximab for CD20+ ALL, outpatient lab follow-up, intrathecal chemotherapy and appropriate referral for allogeneic transplant occurred 50-80% of the time. Provider documentation was appropriate <50% of the time. Conclusions: Based on these findings, we established a standard algorithm of care for ALL patients at LBJGH, enhanced provider education through the design and distribution of teaching tools, created a checklist to facilitate handoffs between providers and established expectations for documentation. In the future, we would also like to add a patient navigator to further improve coordination of care.

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