High Complete Remission (CR) Rates and Reduced Early Mortality with High Dose Ara-c (HiDAC) and Mitoxantrone (MITO) Induction Chemotherapy for Older (age>60) High Risk Patients with Acute Myeloid Leukemia (AML)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3290-3290
Author(s):  
Muthalagu Ramanathan ◽  
Zheng Zhou ◽  
Jan Cerny ◽  
Glen D Raffel ◽  
Laura Petrillo-Deluca ◽  
...  
Keyword(s):  
High Risk ◽  
Median Time ◽  
Induction Chemotherapy ◽  
Cardiac Toxicity ◽  
Remission Induction ◽  
High Dose ◽  
Induction Regimen ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract Abstract 3290 Background: Patients with high risk AML, defined as those with age > 60 years or multiple medical co-morbidities determined by Charleston comorbidity index (CCI) carry a poor prognosis and inferior outcomes after 7+3 induction chemotherapy. CR rates tend to range from 6–51% and induction death rates between 9–48%. We present here a single institution experience of high risk AML patients treated with an induction regimen consisting of high dose mitoxantrone and cytarabine (HiDAC/MITO). Methods: We performed a retrospective analysis of all patients with AML who received HiDAC/MITO induction from January 2009- January 2010 at our institution. Patients with age ≥60 or age <60 with high CCI received HiDAC at 3gm/m2 over three hours on days 1 to 5 plus MITO 80mg/m2 once on day 2. Effect of other high risk features including poor risk cytogenetics, therapy related AML (t-AML), AML with prior antecedent hematological disorder (AHD) and relapsed AML on treatment outcome were also evaluated. The primary endpoints of the study were CR (defined as bone marrow blasts <5%) at day 30 and treatment related mortality within 30 days of initiation of treatment. End of follow-up was June 30, 2010. Results: 20 AML had received HiDAC/MITO for remission induction. The median age was 66.5 years (range 47 to 78), those with age ≥ 70 was 8 (40%). CCI was ≥ 5 in 18 (90%) patients. Other high risk features included high risk cytogenetics in 8 (40%) and non-denovo AML (AML with AHD, t-AML or relapsed AML) in 11 (55%). Overall CR rate was 17 (85%, CI: 61%-96%) and 3 (15%) patients had refractory disease. There was no treatment related mortality. Median time to neutrophil recovery (>1000/ul) was 27 (range 19 to 37) days and median time to platelet recovery (>100,000/ul) was 28 days (range 23 to 44) days. Patients with non–denovo AML were more likely to be refractory to treatment or relapse after day 30. Median follow up of the entire cohort is 288 (range 29 to 530) days. 3 month and 6 month overall survival (OS) was 94.7% and 73.3% and progression free survival (PFS) 93.8% and 87.5%, respectively. The median OS was 410 days (CI: 243-*); (denovo 410 vs. others 381 days). Median PFS is 524 days (CI: 381-*); (denovo *not reached vs. others 381 days). 11(55%) patients were able to proceed to autologous (4) or allogeneic (7) stem cell transplantation (SCT) after receiving HiDAC/MITO. The time to transplant ranged from 44 to 195 days. Median OS of the patients who underwent SCT is 524 days versus 269 days for the non transplant group (p =0.0038). The HiDAC/MITO induction regimen was well tolerated. Cardiac toxicity defined by symptomatic CHF was noted in 6/20 patients. Of the six patients 2 had prior cardiac history and 1 had prior anthracycline exposure and 1 had both anthracycline exposure and cardiac history. Cardiac toxicity was delayed and identified by echo at a median of 90 range (42 to139) days after induction chemotherapy. None of these patients died from cardiac toxicity. Conclusions: In this high risk AML population, HiDAC/MITO induction was well tolerated and demonstrated an overall response rate of 85% and no induction deaths, allowing a substantial number (55%) of patients to proceed to SCT. Contrary to our expectations advanced age or multiple medical co-morbidities did not affect CR rate or survival, thus high lighting the utility of this regimen for high risk newly diagnosed elderly patients with AML. Disclosures: No relevant conflicts of interest to declare.

High Response RATE and NO Treatment Related Mortality After Brentuximab Vedotin Salvage Therapy Followed by Reduced Intensity Conditioning Regimen Allogeneic STEM CELL Transplantation (RIC-ALLO) in Patients with CD 30+ Lymphomas

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4526-4526 ◽  
Author(s):  
Sabine Furst ◽  
Reda Bouabdallah ◽  
Diane Coso ◽  
Roberto Crocchiolo ◽  
Jean El-Cheikh ◽  
...  
Keyword(s):  
Disease Control ◽  
Median Time ◽  
Salvage Therapy ◽  
Autologous Transplantation ◽  
Brentuximab Vedotin ◽  
High Dose ◽  
Term Survival ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract Abstract 4526 Introduction: Patients with relapsed or refractory Hodgkin (HL) and systemic anaplastic large cell lymphomas (sALCL) have poor outcome. RIC-allo might represent an attractive treatment option with curative potential for some patients (pt), but relapse or progression remain the major cause of failure. Pre-transplant disease control is the most important prognostic factor for long term survival and therefore salvage strategies to improve response rates are crucial. Recently, Brentuximab vedotin (BV), a antibody-drug conjugate, has been demonstrated to induce high tumor responses with moderate adverse effects in those high risk pt. Aim and methods: To analyse retrospectively the outcome of pt with CD 30+ HL and sALCL who underwent RIC-allo after BV salvage therapy in our center. BV was administered intravenously (iv) at 1.8mg/kg over 30 minutes every three weeks in the outpatient department. Results: Nine adult pt with histological proved CD30+ lymphomas underwent RIC-allo between February 2010 and Mai 2012. The median age was 36 years (range, 21–59) with 56% males. Diagnosis were HL in 6 pt (67%) and sALCL ALK+ in 3 pt (33%). All pt had highly advanced disease and received a median of 3 prior chemotherapy lines (range, 2–5) including autologous transplantation (78%) before BV treatment: Two pt had primary refractory disease (22%), 2 pt were refractory to front line chemotherapy (22%) and 5 pt were refractory to the most recent treatment (56%). RIC-allo consisted in Fludarabine 150mg/m2 iv (Flu), Busulfan 260mg/m2 iv and ATG (Thymoglobuline) 5mg/kg for matched sibling (2 pt) and 10/10 matched unrelated donors (2 pt); Cyclophosphamide 29mg/kg (Cy), Flu 150 mg/m2 and low dose total body irradiation (TBI) 200cGy for related haploidentical donors (4 pt) and Cy 50mg/kg, Flu 200mg/m2 and TBI 200cGy for one cord blood recipient. Graft versus host disease (GvHD) prophylaxis was either Ciclosporine (CSA) alone or CSA and Mycophenolatemofetil (MMF), while pt with haploidentical donors had posttransplant high dose Cy (100mg/kg). Pt received a median of 7 BV infusions (range, 4–9) before RIC-allo. One pt had autologous transplantation followed by RIC-allo in a tandem procedure. The median time from the first BV infusion to RIC-allo was 189 days (range, 75–391) ? All pt achieved objective best responses after 2 to 3 cycles of BV. At time of RIC-allo, 6 pt were in CR (67%) and 3 pt in PR (33%). All pt engrafted. Three pt developped grade 2 acute GvHD and 2 pt extensive chronic GvHD. After a median follow-up of 275 days (range, 90–872), 7 pt are in CR (78%). Two pt with sALCL experienced relapse at a median time of 87 days after RIC-allo (54, 120), whereas 1 pt died at day 274 of disease progression. No treatment related mortality was observed. Conclusion: Although the study population is small and the follow-up is short, BV as salvage treatment for advanced CD30+ lymphomas may allow to reduce tumour burden to proceed to RIC-allo with sufficient disease control to benefit from a graft versus lymphoma effect. No negative impact on engraftment, GvHD or survival occurred. Randomized prospective trials are necessary to further investigate the role of BV in pre- and post-transplant treatment strategies. Disclosures: No relevant conflicts of interest to declare.

Intensive Consolidation with Clofarabine and Intermediate-Dose Cytarabine (CLARA) in Patients with High-Risk AML in First CR: The ALFA-0702 Pilot Study.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1934-1934 ◽  
Author(s):  
Xavier Thomas ◽  
Ida Lobe ◽  
Emmanuel Raffoux ◽  
Nicolas Boissel ◽  
Quoc-Hung Le ◽  
...  
Keyword(s):  
Pilot Study ◽  
High Risk ◽  
Median Time ◽  
Remission Induction ◽  
High Dose ◽  
Antibacterial Prophylaxis ◽  
Younger Adults ◽  
Historical Series ◽  
Grade 3 ◽  
Intermediate Dose

Abstract Introduction. One standard option for consolidation chemotherapy in younger patients with acute myeloid leukemia (AML) in first CR (CR1) is based on 3 to 4 repeated cycles of high-dose cytarabine (HDAC), according to the CALGB schedule (RJ. Mayer, NEJM 1994). Nevertheless, relapse incidence remains high, especially in those with high-risk AML features and no available donor for allogeneic stem cell transplantation (SCT). Combination of clofarabine with intermediate-dose cytarabine (CLARA) has been reported to induce promising response rate in high-risk AML patients (S. Faderl, Blood 2005 and 2006). We thus tested the feasibility and safety of CLARA consolidation in these patients. Methods. In this 2-center ALFA-0702 pilot study, all younger adults with high-risk AML in CR1 and no possibility of conventional SCT were eligible to receive three CLARA cycles. Patients with good-risk AML (core binding factor, NPM1+/FLT3-ITDwt, or CEBPA+/FLT3-ITDwt) were not eligible and received standard HDAC consolidation. Each CLARA cycle consisted of 1,000 mg/m2/d cytarabine day 1–5 and 40 mg/m2/d clofarabine day 2–6. Planned interval between two consecutive cycles was 35 days. All patients received oral antibacterial prophylaxis with amoxicillin or levofloxacin. Results. Between February 2007 and July 2008, 19 patients aged 22 to 63 years (median, 48 years) were enrolled. All had previously received remission induction according to ALFA protocols. At diagnosis, cytogenetic and molecular findings were as follows: FLT3-ITD (#6), abns of chromosome 5 or 7 (#3), complex karyotype (#1), 3q abn (#1), t(6;9) (#1), 11q23 abn (#1), normal karyotype or various abns (#6). At the present time, a total of 37 CLARA cycles are evaluable for safety. Myelosuppression was relatively rapid and profound. The median time to reach a PMN count less than 0.5 x 109/L was 8 days (range, 6–11). All cycles required platelet transfusions. The median time from cycle initiation to neutrophil recovery (≥ 0.5 x 109/L) was 28 days (range, 17–48), without differences between cycles 1, 2, or 3. However, probably due to non-hematological events, the median time between two consecutive cycles was 43 days (range, 39–79) between cycle 1 and 2, and 48 days (range, 42–78) between cycle 2 and 3. Main clinically relevant non-hematologic toxicities were sepsis (#14), Grade 3/4 nausea/vomiting (#13), Grade 3/4 mucositis (#4), and fungal (#3) or VZV (#1) infection. One patient experienced a curious unexpected and transient CNS event with a mixed sensitive-motor unilateral presentation and cervical hypersignal at MRI. One patient died from a septic shock after the second cycle. Three patients received only two cycles because of an adverse event (fungal infection, liver toxicity, CNS toxicity). Two additional patients received reduced intensity conditioning SCT after one and two CLARA cycles, respectively. Both are alive in CR1 six and four months after SCT, respectively. Even if the follow-up is still relatively short (median, 7 months), only one patient relapsed after 11 months of CR1 duration (the one with t(6;9) translocation). When compared to a historical series of 28 CR patients with similar eligibility criteria treated in the previous ALFA-9802 trial by HDAC consolidation, a gain in disease-free survival might appear (estimated 12-month DFS, 75 versus 57%). Conclusion. Administration of repeated CLARA consolidation cycles is feasible in younger adults with AML in CR1. However, the high rate of infections leads to recommend a careful patient monitoring maximizing infectious prophylaxis and avoiding out-patient management. The randomized ALFA-0702 Phase 2 trial will be initiated in Q4 2008 by the ALFA group in order to prospectively compare these two consolidation approaches in terms of anti-leukemic efficacy.

A Network of Treatment Centers and Standardisation of Treatment Protocol Leads to Reduction in Mortality in Acute Promyelocytic Leukemia (APL)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4317-4317 ◽  
Author(s):  
Anand P. Jillella ◽  
Farrukh Awan ◽  
Ravindra B. Kolhe ◽  
Jeremy M Pantin ◽  
Devi D Morrison ◽  
...  
Keyword(s):  
High Risk ◽  
High Mortality ◽  
Causes Of Death ◽  
Population Based ◽  
Low Risk ◽  
Recent Analysis ◽  
Cumulative Survival ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract Abstract 4317 Background: APL is widely accepted as a curable leukemia with most multi-institutional studies showing very low treatment related mortality. This is in contrast to treatment in clinical practice outside the study population where the treatment related mortality is higher. A few recent population based studies show that mortality maybe as high as 30% in APL patients during induction. A recent analysis of SEER data from 13 population-based cancer registries with 1400 APL patients in the US showed that 17% of all patients and 24% of patients greater than 55 years of age die within one month of diagnosis. Swedish registry data and Brazilian data also show this high mortality during induction. The most common causes of death are bleeding, infection, differentiation syndrome and multi-organ failure. Patients who survive induction have an excellent cure rate with few late relapses. Hence, decreasing early deaths is a high priority both at experienced as well as smaller centers with limited leukemia treatment experience in this highly curable disease. Methods: At Georgia Health Sciences University, between 7/2005 and 6/2009, 19 patients were diagnosed with APL. Seven patients (5 high-risk and 2 low-risk) died during induction resulting in an unusually high mortality rate of 37%. All patients who survived induction are still in remission at present. The high early death rate prompted us to develop a simple, 2 page treatment algorithm that focuses on quick diagnosis, prompt initiation of therapy, and proactive and aggressive management of all the major causes of death during induction. We also developed a network of physicians in smaller community based treatment centers and gave them access to our protocol and helped them manage these patients in the induction period with the hypothesis that this standardized treatment approach will result in decreasing induction mortality. Results: From 11/2010 to 7/2012, we treated 5 patients at GHSU and helped manage 4 patients at 2 outreach sites. The age range was 30 to 60; two patients were high-risk, 6 intermediate- and one low-risk. In the pre-algorithm cohort the cumulative survival was 63.1% at 1 year with all deaths happening within 31 days. In contrast, after the implementation of a standardized algorithm the cumulative survival was 100% with no deaths during the induction or subsequent follow-up period, log rank p-value=0.05, with a median follow-up of more than 4-years in surviving patients. Conclusions: While we recognize that this is a small cohort, our own experience and a similar approach pioneered by investigators in Brazil clearly shows that this centralized, algorithm-based management under the direct supervision of a leukemia expert can be an effective intervention to decrease early deaths in APL. Based on the Brazilian experience an international consortium was formed to reduce the mortality and interim data show a reduction in early mortality to 7.5% with this networking of treatment centers. We believe our experience warrants large scale implementation with development of a network of physicians and standardization of treatment in the United States to improve early outcomes in this highly curable leukemia. Disclosures: Awan: Allos Therapeutics: Speakers Bureau.

First-LINE Treatment With High-Dose Dexamethasone Terapy For Adult Primary Inmune Thrombocytopenia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1081-1081
Author(s):  
Dana Diaz-Canales ◽  
Maria Rosario Prieto-Bonilla ◽  
Maria Eva Mingot-Castellano ◽  
Ana Isabel Heiniger Mazo
Keyword(s):  
High Risk ◽  
Median Time ◽  
High Dose ◽  
Similar Response ◽  
Line Treatment ◽  
First Line ◽  
High Dose Dexamethasone ◽  
Number Of Patients ◽  
First Line Treatment

Abstract Introduction Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder with a very variable outcome. Bleeding manifestations and platelets count are considered the main criteria to start treatment in these patients. The initial recommended therapy are corticosteroids and intravenous immunoglobulin (IgsIV). The aim of our study is the description of efficacy and safety of high-dose dexamethasone (Dx) used as frontline therapy in newly diagnosed ITP patients. Methods A series of patients diagnosed in our centre from March 2009 to August 2012 has been studied. They have received first-line treatment with Dx (40 mg/d four consecutive days every 2 or 4 weeks) for 1 to 6 courses. Sex, age, cardiovascular risk factors, reasons to treat, response, courses of treatment, complications and relapse rate were recorded and analyzed. Results Our series of twenty-nine patients, 18 women (62%) and 11 men (38%), had a median age of 54 years (range 16-92 years). Twenty-five patients (86%) were treated after low platelet counts (30x 10e9 / L) with or without clinical bleeding, whereas the other four patients were treated as a surgery preparation. One patient received a reduced dose of Dx (20 mg/d x 4 days) because of comorbidities and high risk of infection. In thirteen patients, IgsIV were added to Dx in the first course (1g/kg/d x 2 days), because of high bleeding risk or more severe bleeding at diagnosis. Platelets count at baseline was 15x109/ L (range 1-29 x109/ L). Ninety-three percent of patients responded after the first course of Dx (69% complete response CR, 24% partial response PR), and 45% of the patients did not require additional Dx treatment. The median time to reach a response was 5 days since the first day of treatment (range 2-60). The sixteen patients who need more than one course received a median of 4 (range 2-10), all of them without IgsIV. After a median follow-up of 14 months (range 2-45), 69% of these patients maintained the response without further treatment. Therefore, the overall response of the series reaches 83%. After 6 courses of treatment, 5 subjects did not achieved response and were classify as corticosteroid dependent. Of these, one patient was splenectomized and at present he remains at CR after 30 months of follow up. Another patient is waiting for splenectomy, and other three received thrombopoietin analogs, remaining all them in CR under treatment. Thirteen patients received a combination of Igs and Dx in the first course due to high risk of bleeding (platelets less than 20 x 10e9/L and hemorrhagic manifestations). Eleven of them (81%) achieved response (4 PR, 7CR) at a median time of 4 days (range 2–60). After the first course of treatment, 61% (8 of 13) of patients receiving both IgsIV and Dx responded, vs 35% (5 of 16) of those treated only with Dx. This difference was not statistically significant, probably because of the small number of patients in our series. All patients treated with IgsIV and Dx in the first course got the best response after 4 cycles of dexamethasone, compared to 75% of subjects treated with Dx for 4 to 6 courses. Dx was usually well tolerated, since only 13% of the patients experienced side effects: one case of hypertension, another patient developed hyperglycemia associated to corticosteroids and other two presented mild transient steroid psychosis episodes. Infectious events were not observed. Conclusions Treatment with high-dose dexamethasone as first-line treatment for ITP is a good alternative to prednisone because it shows a high efficacy and a good safety profile. In our experience, the association of IgsIV and Dx in the first course may improve the response rate and decrease the total dose of steroids needed to achieve a similar response. Disclosures: No relevant conflicts of interest to declare.

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.

High Dose Valaciclovir As CMV Prophylaxis in Allogeneic Hematopoietic Stem Cell Recipients at High Risk of CMV Reactivation

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 13-14
Author(s):  
Genevieve Douglas ◽  
Michelle K Yong ◽  
Shio Yen Tio ◽  
Maggie Chau ◽  
Joe Sasadeusz ◽  
...  
Keyword(s):  
Stem Cell ◽  
Viral Load ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Median Time ◽  
Standard Dose ◽  
High Dose ◽  
Cmv Prophylaxis ◽  
Cmv Reactivation

Background Cytomegalovirus (CMV) is a common, potentially devastating complication of allogeneic haematopoietic stem cell transplantation (alloHSCT). Universal antiviral prophylaxis strategies including letermovir are effective, but unsubsidised in Australia. Prophylactic ganciclovir or valganciclovir are challenging due to myelotoxicity. Valaciclovir demonstrates anti-CMV activity in high doses, but little current data explore prophylaxis in the alloHSCT setting, particularly in haploidentical transplantation. We aimed to evaluate the clinical efficacy and tolerability of high dose valaciclovir (high dose VALA) as CMV prophylaxis in high risk patients undergoing alloHSCT. Methods This study was completed at the Royal Melbourne Hospital, Melbourne Australia. We performed a retrospective analysis of alloHSCT recipients at high risk of CMV reactivation (defined as recipient and/or donor CMV seropositivity, and undergoing T-cell depletion, haploidentical or umbilical cord stem cell transplantation). Patients transplanted between July 2018 - June 2019, treated with high dose VALA (2g TDS) from day +7 to +100 and beyond were compared to a historical cohort (transplanted between July 2017 - June 2018) on standard dose valaciclovir (std dose VALA) (500mg BD until engraftment then 500mg daily). We compared the rates and time to reach a CMV threshold of 400 IU/ml, at which point pre-emptive CMV therapy was commenced. Tolerability was also evaluated. Results Patient demographics are described in Table 1. Of the standard dose VALA cohort, (median follow-up 259 days), 23/31 (74%) developed a viral load &gt;400 IU/mL, requiring pre-emptive CMV therapy. None had CMV disease. Median time to viral load &gt;400 IU/mL was 39 days (range 13 - 68). Of the high dose VALA cohort (median follow-up 209 days), 11/25 (44%) developed a viral load &gt;400 IU/mL, requiring pre-emptive CMV therapy. Of these 11 cases, 7 patients had viral load &gt;400 IU/mL while on high dose VALA prior to D+100, 3 patients had ceased high dose VALA prior to D+100 due to intolerance and in 1 patient this occurred post D+100 while on high dose VALA. One patient developed CMV (gut) disease following early cessation of high dose VALA, whilst on standard dose VALA. Median time to reactivation &gt;400 IU/mL was 64 days (range 26-170). Time to reactivation &gt;400 IU/ml was significantly different between the standard vs high dose VALA cohorts (mean ± SEM; 37.9 ± 2.7 vs 67.8 ± 11.3 days, **p=0.0015). Median duration of high dose VALA prophylaxis was 50 days (range 11-288). Seven (28%) patients continued high dose VALA to day +100 and beyond. Intolerance led to early cessation in 10 (40%) patients (acute kidney injury, n=6; cytopenia, n=3; both, n=1). Other patients ceased due to requirement for definitive CMV therapy (n=6) and unclear reasons (n=2). Conclusions In high risk alloHSCT recipients, high dose VALA is an effective CMV prophylactic strategy resulting in lower CMV reactivation rates, and delays CMV reactivation. This may reduce requirements for myelotoxic CMV treatment during the early post-engraftment period and need for inpatient admission. CMV infection following high dose VALA cessation remains a risk, particularly when dose reductions have occurred due to toxicity, and intolerance and ongoing monitoring is required. Treatment tolerability remains a limitation. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Valaciclovir, for CMV prophylaxis

Pre-Transplant 5-Azacitidine (Vidaza®) May Improve Outcome of Allogeneic Hematopoietic Cell Transplantation (HCT) in Patients with Myelodysplastic Syndrome (MDS).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3664-3664 ◽  
Author(s):  
Teresa Field ◽  
Janelle Perkins ◽  
Melissa Alsina ◽  
Ernesto Ayala ◽  
Hugo F. Fernandez ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Prospective Trial ◽  
High Dose ◽  
Unrelated Donor ◽  
Conditioning Treatment ◽  
Risk Of Relapse ◽  
Related Mortality

Abstract Most patients with MDS are older than 60 yrs and, because of age, many have previously been excluded from HCT due to the high risk of transplant related mortality. Reduced intensity conditioning has decreased regimen related mortality in HCT and has increased the age of patients for whom this treatment is offered. There remains substantial risk of relapse after HCT especially in patients with > Int-1 MDS who benefit the most from immediate HCT. One strategy to suppress leukemia burden and potentially decrease the risk of relapse is pre-transplant treatment with 5-azacitidine (Vidaza®). This DNA hypomethylating drug is FDA approved for the treatment of MDS. We analyzed the outcome for 34 MDS patients who received a myeloablative HCT from an HLA compatible sibling or unrelated donor from July 2004 through June of 2006, to investigate the potential impact of pre-transplant 5-azacitidine on response and post-transplant relapse. Fourteen of thirty-four patients received a median of 2 (1–7) cycles of 5-azacitidine prior to HCT. Median age was 59 (49 – 69) yrs. Diagnosis and IPSS category included MDS (8) [Int-1 (1) and Int-2 (7)], MDS-AML (5) and CMML (1). Two patients had induction chemotherapy with residual MDS prior to 5-azacitidine. Subsequent to 5-azacitidine: ten responded [CR (2), PR (1) improvement (7)] three progressed and one was not evaluable. The IPSS category after 5-azacitidine treatment and prior to HCT was Int-2(1), Int-1 (4), and Low (5; 3 in CR) in addition to AML (2) and CMML (1). One was unable to assess. The median follow-up in the survivors is 191 (47 – 524) days. Of the fourteen 5-azacitidine treated patients, none have relapsed post-HCT including patients who progressed on 5-azacitidine. Four have died from non-Hodgkins lymphoma (1), DAH (1), adenovirus pneumonia (1) and chronic GVHD (1). Ten are alive in remission, two for greater than one year. Twenty patients did not receive 5-azacitidine. Diagnosis and IPSS category included MDS (9) [Int-1 (3) and Int-2 (6)], MDS-AML (9) and CMML (1) and one not determined due to lack of cytogenetics. Their median age was 53 (33 – 68) yrs. Treatment included supportive care, induction chemotherapy (9) and SCIO-469 (1). IPSS distribution prior to HCT was Int-2 (7), Int-1 (5) Low (5; 4 in CR); in addition to AML (1) and CMML (1). One was unable to assess. The median follow-up in the survivors is 420 (21 – 742) days. Ten of twenty are alive without relapse and eight have relapsed. Five have died, with relapse (3), fungal pneumonia (1) or multi-organ failure (1). The 1 year K-M estimates of overall and progression free survivals are 64% (SEM 15%) and 64% (SEM 15%), respectively for 5-azacitidine group and 70% (SEM 11%) and 51% (SEM 13%) for non-5-azacytidine group. We conclude from this preliminary analysis that pre-HCT conditioning treatment with 5-azacitidine may reduce the risk for MDS relapse after allogeneic transplant in higher risk patients. In addition to its direct anti-tumor effect, 5-azacitidine may sensitize neoplastic cells to the effects of high dose chemotherapy or promote the expression of antigens critical to effective graft-vs-tumor response. This treatment strategy will be evaluated in a prospective trial to investigate the role of pre-transplant 5-azacitidine on transplant outcomes in patients with higher risk MDS.

Safety and efficacy of risk-adapted cyclophosphamide, thalidomide, and dexamethasone in systemic AL amyloidosis

Blood ◽  
2006 ◽  
Vol 109 (2) ◽  
pp. 457-464 ◽  
Author(s):  
Ashutosh D. Wechalekar ◽  
Hugh J. B. Goodman ◽  
Helen J. Lachmann ◽  
Mark Offer ◽  
Philip N. Hawkins ◽  
...  
Keyword(s):  
Randomized Study ◽  
High Dose ◽  
Al Amyloidosis ◽  
Prior Therapy ◽  
Oral Regimen ◽  
Risk Patients ◽  
High Dose Melphalan ◽  
Treatment Related Mortality ◽  
Related Mortality

AbstractHigh-dose melphalan with stem-cell transplantation is believed to be the most effective treatment for systemic light-chain (AL) amyloidosis, but many patients are ineligible because of the extent of their disease, and treatment-related mortality (TRM) remains substantial. We report the use of a risk-adapted oral regimen of cyclophosphamide, thalidomide, and dexamethasone (CTD) or attenuated CTD (CTDa) in 75 patients with advanced AL amyloidosis, including 44 patients with clonal relapse after prior therapy. Fifty-one (68%) patients received CTD and 24 (32%) received CTDa. A hematologic response occurred in 48 (74%) of 65 evaluable patients, including complete responses in 14 (21%) and partial responses in 34 (53%) cases. Median estimated overall survival (OS) from commencement of treatment was 41 months, and from diagnosis median was not reached with a median follow-up of 22 months. Three-year estimated OS was 100% and 82% among complete and partial hematologic responders, respectively. Toxicity necessitating cessation of therapy occurred in 8% and was at least grade 2 in 52% of patients. TRM was 4%. The clonal response rates to CTD reported here are higher than any previously reported nontransplantation regimen in AL amyloidosis, and risk adaptation allows its use in poorer risk patients. CTD merits prospective randomized study.

scholarly journals Tandem Autologous Followed By Nonmyeloablative Allogeneic Transplantation in Relapsed High Risk Follicular Lymphoma Leads to Excellent Long Term Progression-Free Survival after 8 Years of Follow-up

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4677-4677
Author(s):  
Magalie Tardif ◽  
Imran Ahmad ◽  
Nadia M. Bambace ◽  
Lea Bernard ◽  
Lambert Busque ◽  
...  
Keyword(s):  
High Risk ◽  
Follicular Lymphoma ◽  
Median Time ◽  
Progression Free Survival ◽  
Disease Status ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Free Survival

Abstract Many new therapeutic agents have been approved for follicular lymphoma (FL) but none appear to be curative. Despite novel agents, some patients (pts) experience early relapse, become chemorefractory or suffer transformation into more aggressive lymphomas. Options for these pts are limited. High dose chemotherapy with autologous stem transplant (ASCT) prolongs progression free survival (PFS) and overall survival (OS) in FL pts in first relapse and registry data shows favorable outcome with ASCT in cases of histologic transformation. However, ASCT is usually not curative. Myeloablative allogeneic transplant (MT) has produced long term PFS but is hampered by significant non relapse mortality (NRM) while nonmyeloablative transplant (NMT) has a higher relapse rate compared to MT especially in high risk pts. Finally, many transplant studies have excluded these high risk pts such as those with chemorefractory or transformed disease. We hypothesized that a tandem transplant consisting of an ASCT followed by a NMT would confer the same benefit as a MT without the associated high NRM by separating the high dose chemotherapy from graft versus host disease (GVHD) while preserving the graft versus lymphoma effect. The goal of our study was to improve long term PFS in high risk FL pts. We therefore initiated a prospective protocol in April 2003, for pts with high risk relapsed FL as defined by chemorefractory disease, early 1st relapse, >1st relapse or transformation into aggressive histology. At least one therapy was attempted to document chemosensitivity prior to ASCT. However, regardless of disease status prior to transplant, pts underwent ASCT followed 3 months later by an outpatient NMT from an HLA-identical sibling. NMT comprised 5 days of fludarabine 30 mg/m2/day and cyclophosphamide 300mg/m2/day followed by an infusion of >2x106CD34+ cells/kg. GVHD prophylaxis, chosen to take advantage of the low incidence of acute (a) GVHD and the putative protective effect of chronic (c) GVHD, consisted of tacrolimus starting on day (D) - 8 to achieve levels of 8-12 nmol/L then tapered off by D+100 or D+180 depending on disease risk and of mycophenolate mofetil 1g bid from D+2 to D+50. We previously reported on 27 pts with a follow-up (f/u) of 3 years (yrs). We now report a larger cohort of 40 pts with a median f/u of 8 yrs. Up until July 2015, 40 pts were enrolled with a median age of 50 yrs (34-65). Pts had previously been treated with a median of 3 lines of therapy (2-6). Median time from diagnosis to ASCT was 33 months. Disease status at ASCT was: 14 CR, 16 PR and 10 refractory. Conditioning for ASCT included BEAM/BEAC (n=39), and Cy-TBI (n=1). In addition, 4 pts received radiotherapy after ASCT to sites of previously bulky disease. Median time between ASCT and NMT was 138 days (75-238). Pre NMT disease status was: 25 CR, 12 PR and 3 refractory. Engraftment was prompt in all pts after ASCT and median neutrophil and platelet recovery were respectively 13 days (0-19) and 0 day (0-18) post NMT. Seven pts (18%) developed aGVHD: 2 grade II and 5 grade III. Overall, 29 pts (73%) developed cGVHD: 1 mild, 13 moderate and 15 severe according to NIH revised criteria. Median time to discontinuation of immunosuppression was 22 months. To date, 2 pts have progressed at 11 and 59 months post NMT (one died from relapse and one is now in CR after chemotherapy and DLI) and 5 pts died from either GVHD related complications (n=4) or unknown cause (n=1). All pts alive at last f/u were in CR. With a median f/u of 8 yrs in surviving pts (1-12), OS is 95% at 3 and 5 yrs and 82% at 8 yrs. PFS is 92% at 3yrs, 89% at 5 yrs and 80% at 8 yrs. NRM and relapse rate at 8 yrs are 18% and 6% respectively. Based on our current results in 40 pts, we conclude that ASCT followed by sibling NMT for high risk relapsed FL is associated with excellent disease response and PFS. Furthermore, this tandem strategy appears to be safe and well tolerated. The incidence of cGVHD remains high but could in part explain the impressive PFS in this high risk cohort. This approach should now be further explored in a multi institution setting, include matched unrelated donors and consider the addition of rituximab post-transplant to reduce the incidence and severity of cGVHD with the hope that relapse will not be increased. Figure 1 Figure 1. Disclosures Busque: Pfizer: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau.

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