Prophylaxis of Cytomegalovirus (CMV) Infection and Disease after Unrelated-Donor Umbilical Cord-Blood Transplantation (UCBT) with Intravenous Ganciclovir or Oral Valganciclovir.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5460-5460
Author(s):  
Guillermo Sanz ◽  
Susana Cantero ◽  
Ignacio Lorenzo ◽  
Barbara Benlloch ◽  
Luis Benlloch ◽  
...  
Keyword(s):  
Cumulative Incidence ◽  
High Dose ◽  
Cmv Infection ◽  
Intravenous Ganciclovir ◽  
Cell Dose ◽  
Intravenous Acyclovir ◽  
Oral Valganciclovir ◽  
Cmv Disease ◽  
To Receive ◽  
Cmv Prophylaxis

Abstract Prophylactic antiviral treatment for prevention of CMV infection and disease could be valuable after UCBT, where the incidence of CMV infection is very high. The purpose of this study was to evaluate the efficacy and safety of a strategy of prophylaxis of CMV infection and disease in patients undergoing UCBT. From May 1997 to May 2005, 52 CMV-seropositive adults with hematologic malignancies (15 in advanced phases) underwent UCBT at our institution. CMV prophylaxis consisted of high-dose intravenous acyclovir from day −5 until engraftment followed until day +100 by intravenous ganciclovir (GAN, 5 mg/kg per day 3 to 7 days per week) in the first 38 patients and by oral valganciclovir (VALGAN, 900 mg per day as a single daily dose) in the last 14 patients. All patients received thiotepa, busulfan, cyclophosphamide and antithymocyte globulin as conditioning, cyclosporine and prednisone as GVHD prophylaxis, and filgrastim from day +7 until engraftment. All 52 patients were considered as evaluable for efficacy and those actually receiving the scheduled CMV prophylaxis with GAN or VALGAN were considered evaluable for toxicity. Median age was 33 yr (range, 18–47), HLA match was 6/6 in 2 (4%), 5/6 in 19 (37%), and 4/6 in 31 cases (60%), and median number of nucleated and CD34+ cells infused was 2.1 x 10E7/kg (range, 0.9–5) and 0.9 x 10E5/kg (range, 0.1–5.7) respectively. The cumulative incidence of CMV infection was 46% at day 100 and 54% at days 180 and 365, and the cumulative incidence of CMV disease was 2% at day 100, 8% at day 180 and 15% at day 365. No clear differences between patients taking GAN or VALGAN were observed in the cumulative incidence of CMV infection (45% and 50% at day 100 and 53% and 57% at days 180 and 365, respectively; P=0.89) and CMV disease (3% and 0% at day 100, 10% and 0% at day 180 and 16% and 14% at day 365, respectively; P=0.75). Twenty-two patients assigned to receive GAN and 8 patients assigned to receive VALGAN experienced 31 and 11 episodes of other severe infections respectively. GAN was withdrawn in 2 patients due to renal toxicity and VALGAN in 2 patients due to neutropenia. Ten patients (7 receiving GAN and 3 receiving VALGAN) experienced at least one episode of recurrent CMV infection. Two of the 8 patients who developed CMV disease, both with GAN, died from CMV. Higher doses of nucleated (P=0.008) and CD3+ (P=0.04) cells infused, presence of acute GVHD below grade II (P=0.01), and use of Thymoglobulin (P=0.008) were associated with a lower risk of CMV infection. The CD3+ cell dose was inversely associated with the risk of CMV disease (P=0.01). These results suggest that CMV prophylaxis with intravenous GAN or oral VALGAN is both safe and effective to reduce and/or delay the occurrence of CMV infection and disease after UCBT. Further, these data show, for the first time, the importance of the CD3+ cell dose infused and of other characteristics in the development of CMV infection and disease after UCBT.

High dose valacyclovir for cytomegalovirus prophylaxis following allogeneic hematopoietic cell transplantation

2021 ◽  
pp. 107815522110604
Author(s):  
Kelly G Hawks ◽  
Amanda Fegley ◽  
Roy T Sabo ◽  
Catherine H Roberts ◽  
Amir A Toor
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
High Dose ◽  
Cmv Infection ◽  
Allogeneic Hct ◽  
Clinically Significant ◽  
Cmv Disease ◽  
Cmv Prophylaxis

Introduction Cytomegalovirus (CMV) is one of the most common and clinically significant viral infections following allogeneic hematopoietic cell transplantation (HCT). Currently available options for CMV prophylaxis and treatment present challenges related to side effects and cost. Methods In this retrospective medical record review, the incidence of clinically significant CMV infection (CMV disease or reactivation requiring preemptive treatment) following allogeneic HCT was compared in patients receiving valacyclovir 1 g three times daily versus acyclovir 400 mg every 12 h for viral prophylaxis. Results Forty-five patients who received valacyclovir were matched based on propensity scoring to 35 patients who received acyclovir. All patients received reduced-intensity conditioning regimens containing anti-thymocyte globulin. Clinically significant CMV infection by day + 180 was lower in the valacyclovir group compared to the acyclovir group (18% vs. 57%, p = 0.0004). Patients receiving valacyclovir prophylaxis also had less severe infection evidenced by a reduction in CMV disease, lower peak CMV titers, delayed CMV reactivation, and less secondary neutropenia. Conclusion Prospective evaluation of valacyclovir 1 g three times daily for viral prophylaxis following allogeneic HCT is warranted. Due to valacyclovir's favorable toxicity profile and affordable cost, it has the potential to benefit patients on a broad scale as an option for CMV prophylaxis.

Randomized study of valacyclovir as prophylaxis against cytomegalovirus reactivation in recipients of allogeneic bone marrow transplants

Blood ◽  
2002 ◽  
Vol 99 (8) ◽  
pp. 3050-3056 ◽  
Author(s):  
Per Ljungman ◽  
Rafael de la Camara ◽  
Noel Milpied ◽  
Liisa Volin ◽  
Charlotte A. Russell ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Disease Incidence ◽  
Randomized Study ◽  
High Dose ◽  
Allogeneic Bone ◽  
Oral Acyclovir ◽  
Cmv Infection ◽  
Double Blind ◽  
Intravenous Acyclovir ◽  
Cmv Disease

Abstract Oral valacyclovir for cytomegalovirus (CMV) prophylaxis in bone marrow transplantation (BMT) was investigated in a randomized, double-blind, acyclovir-controlled, multicenter clinical trial in recipients of allogeneic BMT who were CMV seropositive (or donor positive) before transplantation and were aged 13 years or older. Patients were randomized before BMT. All initially received intravenous acyclovir (500 mg/m2) 3 times daily until day 28 after transplantation or after discharge, then oral valacyclovir (2 g) or acyclovir (800 mg) 4 times daily until week 18 after transplantation. Evidence of CMV infection, CMV disease, and death were documented for 22 weeks. Primary end points were time to CMV infection (detection of CMV in blood, broncho-alveolar lavage) or CMV disease and survival. Preemptive CMV therapy was permitted. Seven hundred twenty-seven patients were evaluable for efficacy. After the administration of intravenous acyclovir, valacyclovir was significantly more effective than oral acyclovir in reducing the incidence of CMV infection. CMV infection or disease developed in 102 (28%) valacyclovir patients, compared with 143 (40%) acyclovir patients (HR, 0.59; 95% CI, 0.46-0.76; P < .0001). Survival did not differ between treatments (76% and 75% in the valacyclovir and acyclovir groups, respectively). The safety of oral valacyclovir was similar to that of high-dose oral acyclovir. Valacyclovir was more effective than acyclovir in preventing CMV reactivation in BMT recipients and showed a similar safety profile. CMV disease incidence was low, and no differences were observed between oral valacyclovir and acyclovir. Survival was similar in each group. Valacyclovir prophylaxis provides a clinically valuable intervention but must be part of an overall strategy for CMV prevention in BMT.

CMV pneumonitis in a patient with Crohn’s disease taking azathioprine

2021 ◽  
Vol 14 (4) ◽  
pp. e241256
Author(s):  
Timothy Zef Hawthorne ◽  
Rachel Shellien ◽  
Lucy Chambers ◽  
Graham Devereux
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Low Dose ◽  
Antiviral Treatment ◽  
Cmv Infection ◽  
Rare Presentation ◽  
Intravenous Ganciclovir ◽  
Increased Risk ◽  
Oral Valganciclovir

This case report discusses the rare presentation of cytomegalovirus (CMV) pneumonitis in a young patient with moderately severe Crohn’s disease managed with low dose azathioprine. CMV pneumonitis was initially suspected on CT chest images and confirmed by PCR for CMV. She was treated with intravenous ganciclovir and later stepped down to oral valganciclovir. Although this patient had a prolonged and complicated hospital admission, a good clinical outcome was achieved. CMV infection was raised as an early differential and antiviral treatment was started without delay. This case study, therefore, makes the case for increased awareness of the possibility of, and recognition of CMV pneumonitis among healthcare professionals as a way of preventing significant morbidity and mortality. It also raises awareness of checking for slow metabolisers of azathioprine before initiation to look for individuals who may be at increased risk of azathioprine’s adverse effects.

scholarly journals A rare case of cytomegalovirus presentation in a hemodialysis patient

2017 ◽  
Vol 4 (3) ◽  
pp. 79
Author(s):  
Liesbeth De Waele ◽  
Katrien Wierckx ◽  
Anne-Marie Bogaert
Keyword(s):  
Terminal Ileum ◽  
Hemodynamic Instability ◽  
Cmv Infection ◽  
Intravenous Ganciclovir ◽  
Diffuse Abdominal Pain ◽  
Rare Manifestation ◽  
End Stage ◽  
Gastro Intestinal Tract ◽  
Cmv Disease ◽  
Substantial Morbidity

Background: Cytomegalovirus (CMV) infection is a common viral infection in humans with a diverse manifestation, mostly dependent on the host. CMV infection in the immunocompetent host is generally asymptomatic or may present as a mononucleosis syndrome. Infection in immunocompromised patients cause substantial morbidity and mortality.Case representation: We report a rare manifestation of a CMV infection in a 87-year-old male with end-stage renal failure with dialysis dependency and diabetes who presents with diffuse abdominal pain and nausea. Further assessment with a CT scan of the abdomen showed a thickening of the wall of the preterminal ileum, suggestive of focal enteritis. Ileocolonoscopy showed a partial circular ulcerated mucosa of the preterminal ileum, biopsies showed ulcerations, etiology was unknown. A few days later he develops melena and anemia of 7.2 g/dl. Further exploration with gastroscopy was normal. A new colonoscopy showed no abnormalities; however the terminal ileum could not be visualized. An urgent laparotomy was performed because of hemodynamic instability and showed an ulcus of 7 cm with a thickened terminal ileum. An enterectomy of the inflammated part of the ileum was performed. Histopathology of the ulceration showed the presence of CMV inclusions in the vascular endothelium of the capillaires of the ileal segment. Serologic examination showed nonreactive CMV IgM antibodies and IgG antibodies were positive. PCR CMV showed 300 copies/ml (whole blood). Treatment with intravenous ganciclovir was started with good clinical and biochemical response.Conclusions: In the differential diagnosis CMV disease should be considered in any ulceration in the gastro-intestinal tract in the immunocompromised patient.

scholarly journals A comparison of filtered leukocyte-reduced and cytomegalovirus (CMV) seronegative blood products for the prevention of transfusion- associated CMV infection after marrow transplant [see comments]

Blood ◽  
1995 ◽  
Vol 86 (9) ◽  
pp. 3598-3603 ◽  
Author(s):  
RA Bowden ◽  
SJ Slichter ◽  
M Sayers ◽  
D Weisdorf ◽  
M Cays ◽  
...  
Keyword(s):  
Secondary Analysis ◽  
Marrow Transplant ◽  
Disease Rate ◽  
Blood Products ◽  
Cmv Infection ◽  
Primary Analysis ◽  
Probability Of Survival ◽  
Transplant Patients ◽  
Cmv Disease ◽  
To Receive

We performed a prospective, randomized trial in CMV seronegative marrow recipients to determine if filtered blood products were as effective as CMV-seronegative blood products for the prevention of transfusion- transmitted CMV infection after marrow transplant. Before transplant, 502 patients were randomized to receive either filtered or seronegative blood products. Patients were monitored for the development of CMV infection and tissue-documented CMV disease between days 21 and 100 after transplant. Infections occurring after day 21 from transplant were considered related to the transfusion of study blood products and, thus, were considered evaluable infections for the purpose of this trial. In the primary analysis of evaluable infections, there were no significant differences between the probability of CMV infection (1.3% v 2.4%, P = 1.00) or disease (0% v 2.4%, P = 1.00) between the seronegative and filtered arms, respectively, or probability of survival (P = .6). In a secondary analysis of all infections occurring from day 0 to 100 post-transplant, although the infection rates were similar, the probability of CMV disease in the filtered arm was greater (2.4% v 0% in the seronegative arm, P = .03). However, the disease rate was still within the prestudy clinically defined acceptable rate of < or = 5%. We conclude that filtration is an effective alternative to the use of seronegative blood products for prevention of transfusion- associated CMV infection in marrow transplant patients.

scholarly journals Small bowel perforation secondary to CMV-positive terminal ileitis postrenal transplant

2019 ◽  
Vol 12 (11) ◽  
pp. e231662 ◽  
Author(s):  
Kosuke Kato ◽  
Michelle Cooper
Keyword(s):  
Small Bowel ◽  
Rare Complication ◽  
Bowel Perforation ◽  
Lower Abdominal Pain ◽  
Right Hemicolectomy ◽  
Small Bowel Perforation ◽  
Cmv Infection ◽  
Terminal Ileitis ◽  
Intravenous Ganciclovir ◽  
Cmv Disease

Cytomegalovirus (CMV) infection of the gastrointestinal tract is common in immunosuppressed patients; however, small bowel perforation from tissue-invasive CMV disease after many years of immunosuppressive therapy is a rare complication requiring timely medical and surgical intervention. We report a case of a postrenal transplant patient who presented to the emergency department with severe lower abdominal pain with CT of the abdomen/pelvis revealing a small bowel perforation. He underwent an emergent laparoscopic right hemicolectomy, and his histopathology of the terminal ileum was positive for CMV disease. He was successfully treated with intravenous ganciclovir postoperatively. We discuss the pathophysiology, histopathological features and treatment of CMV infection.

P1667ANALYSIS OF RISK FACTORS FOR CMV DISEASE IN KIDNEY TRANSPLANT PATIENTS - SINGLE CENTER STUDY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Vladimir Hanzal ◽  
Janka Slatinska ◽  
Petra Hruba ◽  
Ondrej Viklicky
Keyword(s):  
Risk Factors ◽  
Kidney Transplantation ◽  
Multivariable Analysis ◽  
Graft Function ◽  
Kidney Graft ◽  
Cmv Infection ◽  
Post Transplantation ◽  
Increased Risk ◽  
Cmv Disease ◽  
Cmv Prophylaxis

Abstract Background and Aims Cytomegalovirus (CMV) disease and infection negatively influence outcome of kidney transplantation. The aim of this retrospective study was to analyze risk factors for CMV disease and its influence on kidney graft function and survival. Method 1050 patients underwent kidney transplantation from January 2014 to December 2018 and received calcineurin inhibitor, mycophenolate mofetil and steroid-based immunosuppression. Recipients with PRA&gt;20% received rATG while others had received basiliximab as induction. 825 out of 1050 patients (78.6%) received CMV prophylaxis (D+/R-, n=173; R+, n=652). Patients were followed up to 71 months /median 38 months/. Results CMV tissue invasive disease occurred in 49 out of 1050 patients (4.7%), while CMV infection in 87 patients (8.3%). CMV disease, but not CMV infection, had significant negative influence on graft survival at 5 years post transplantation (p=0.0029). Patients with CMV disease had significantly worse graft function at 4 years post transplantation (p&lt;0.0001). CMV disease occurred in 31 out of 173 patients (17.9%) in D+/R- group vs. 18 out of 652 patients (2.8%) in R+ group. Incidence of CMV infection was 30/173 patients (17.3%) in D+/R- group vs. 57/652 patients (8.7%) with induction therapy. Shortening of CMV prophylaxis was found in 82 patients (9.9%). Leukopenia (≤ 2.0 x 109/L) was observed in 97 (11.7%) patients from those who received CMV prophylaxis, Its shortening significantly increased risk for both CMV infection (20,7% vs. 7.2%, p&lt;0,0001) and CMV disease (8,5% vs. 4,2%, p=0,04). Among most significant risk factors for CMV disease in univariable analysis were CMV mismatch (OR 11, 95% CI: 5,9-20,4; p&lt;0,0001), delayed graft function (OR 2,8, 95% CI: 1,6-5,1; p&lt;0,0001, cadaveric donor (OR 6, 95% CI: 1,5-25,1; p=0,00013) and shortening of CMV prophylaxis (OR 2.1, 95% CI: 0,91-4,86; p=0,08). Multivariable analysis revealed as independent significant predictors of CMV disease DGF (OR 2,29, 95% CI: 1,2-4,3; p=0,01) and CMV mismatch (OR 10,8, 95% CI: 5,7-20,6; p&lt;0.0001) in a model adjusted for type of donor, prophylaxis shortening and leukopenia. Conclusion CMV mismatch is the main independent predictor of CMV disease after kidney transplantation in multivariable analysis.

Results of a Phase I/II-Study on PCR-Based Pre-Emptive Therapy with Valganciclovir or Ganciclovir for Active CMV Infection Following Reduced Intensity Allogeneic Stem Cell Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5011-5011
Author(s):  
ZiYi Lim ◽  
Gordon Cook ◽  
Peter R. Johnson ◽  
Anne Parker ◽  
Mark Zuckerman ◽  
...  
Keyword(s):  
Stem Cell ◽  
Efficacy And Safety ◽  
Cmv Infection ◽  
Reduced Intensity Conditioning ◽  
Intravenous Ganciclovir ◽  
Group A ◽  
Oral Valganciclovir ◽  
Group B ◽  
Cmv Reactivation ◽  
Reduced Intensity

Abstract The advent of reduced intensity conditioning(RIC) protocols for allogeneic haematopoietic stem cell transplantation(HSCT) has reduced the incidence of early transplantation related morbidity largely due to the attenuation of the conditioning intensity. Nevertheless, the incidence of CMV reactivation in these patients remains high. Herein we report the results of a multi-centre randomised prospective study to assess the bioavailability(auc0–12) of ganciclovir in the population of patients undergoing alemtuzumab-based RIC HSCT after oral administration of valganciclovir and secondly, the efficacy and safety of valganciclovir in the treatment of a CMV infection following allogeneic SCT. Recipients of allogeneic bone marrow or peripheral blood stem cell transplants with related or unrelated donors following reduced intensity conditioning, without proven graft versus host disease were eligible for this study. RIC protocols approved for the purposes of this study were FBC(fludarabine, busulphan, alemtuzumab) and FMC(fludarabine, melphalan,alemtuzumab). For inclusion into the study, patients had to have a detectable CMV DNA load in two consecutive blood specimens up to 120 days after transplant. Eligible patients were randomized to 1 of 2 treatment groups: group A received 900 mg oral valganciclovir(2 x 900 mg/d) for 14 days and group B received intravenous ganciclovir 5mg/kg/d twice daily for 14 days. All patients were monitored for 84 days(safety follow-up). pK profiles of ganciclovir were obtained after administration of the study drug in each study arm. pK assessments were scheduled at days 4 and 11. 27 patients were recruited into the study over a 24-month period from Jan 2005 to Dec 2006. The median age was 51 years(range:34–68). The median time to CMV reactivation was 43 days post-HSCT(range:20–114). 18 patients(67%) completed the allocated treatment resulting in CMV DNA load <10 copies/ml at a median of 14 days post-HSCT(range:7–28). In 9 cases, there were changes to the primary treatment regimen. In group A, treatment was modified in 5 cases; 3 due to rising CMV levels, 1 due to drug rash, 1 due to neutropenia. In group B, 4 patients had treatment modification; 3 patients due to rising CMV DNA levels, 1 had neutropenia. None of the patients in the study developed CMV invasive disease. The median value of the systemic clearance of ganciclovir was 11.8 l/h(95%CI: 8–15.6 l/h). The bioavailability of ganciclovir from valganciclovir(expressed as equivalents of ganciclovir) was 73%(95%CI, 34%–112%). The average exposure in the valganciclovir group(36.9 ± 14.9μg.h/ml) was significantly higher than in the ganciclovir cohort(27.9 ±7.5μg.h/ml). As a result, ganciclovir bioavailability in the subjects who received valganciclovir was 79%. In summary, when compared with intravenous ganciclovir, oral valganciclovir had high bioavailability with equivalent efficacy and safety in patients undergoing RIC HSCT. Use of valganciclovir can facilitate the out-patient treatment of patients with CMV reactivation post-HSCT with a potential reduction in hospitalization costs.

scholarly journals Letermovir Is Effective for Prevention of Cytomegalovirus Reactivation in HLA-Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplant Cyclophosphamide

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2858-2858
Author(s):  
Takahide Ara ◽  
Yuta Hasegawa ◽  
Hiroyuki Ohigashi ◽  
Souichi Shiratori ◽  
Atsushi Yasumoto ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Cmv Infection ◽  
Advisory Committees ◽  
Cmv Disease ◽  
Cmv Reactivation

Abstract [Introduction] Cytomegalovirus (CMV) infection is a common viral infection in recipients of allogeneic hematopoietic stem cell transplantation (allo-SCT). Early CMV reactivation after allo-SCT is associated with worse non-relapse mortality (NRM) and overall survival (OS). Recently, T-cell replete HLA-haploidentical SCT using post-transplant cyclophosphamide (PTCy-haplo SCT) has been developed and spread rapidly worldwide. Rationale of this strategy is assumed to be selective and cytotoxic depletion of alloreactive T cells which are responsible for graft-versus-host disease (GVHD), while preserving non-alloreactive T cells which can contribute to fight infections. However, recent studies showed that PTCy-haplo SCT was associated with the increased incidence of CMV infection. Letermovir (LET), a novel anti-CMV agent, which inhibits the CMV DNA terminase complex, was approved for the prevention of CMV reactivation in allo-SCT recipients in 2018 in some countries including Japan based on the result of a phase 3 trial. Our facility performs LET prophylaxis in allo-SCT recipient if either donor or recipient is seropositive CMV. Although LET is effective for the prevention of CMV reactivation in allo-SCT recipients, the clinical effectiveness of LET prophylaxis in PTCy-haplo SCT is not well elucidated. Based on these things, we retrospectively evaluated the efficacy of LET prophylaxis in PTCy-haplo SCT. [Methods] We retrospectively analyzed consecutive 99 recipients who received PTCy-haplo SCT at Hokkaido University Hospital from March 2013 to March 2021. We compared the cumulative incidence of CMV reactivation between the LET prophylaxis group (LET group, 33 patients) and LET non-prophylaxis group (non-LET group, 66 patients). LET was initiated on the day 0 at a dosage of 480mg daily. All patients were monitored for CMV reactivation by using the anti-CMV pp65 monoclonal antibody HRP-C7 assay at least once a week from the time of engraftment. CMV reactivation was defined as the detection of CMV antigen positive cells per 50000 white blood cells, whereas CMV disease was defined by organ dysfunction attributable to CMV. [Results] As baseline patient's characteristics were summarized in Table1, there were no difference between LET and non-LET group in terms of age, sex, underlying disease, disease risk at transplantation, prior transplantation, conditioning intensity, and CMV serostatus. All patients received peripheral blood stem cell transplantation. GVHD prophylaxis consisted of Cy (40-50 mg/kg on day 3 and 4), tacrolimus (from day 5), and mycophenolate mofetil (from day 5). The cumulative incidence of CMV reactivation at 150 days after transplantation in LET group was significantly lower than that in non-LET group (30.3% versus 69.7%; P &lt;.001, Figure1A). Importantly, CMV disease were occurred in three patients without LET prophylaxis (gastritis, enteritis, and retinitis), but not in the patients with LET prophylaxis. The cumulative incidence of NRM at 1 year was similar between the patients with and without LET prophylaxis (17.6% versus 9.2%; P=0.366, Figure1B), as was OS at 1 year (71.5% versus 69.4%; P=0.801, Figure1C). Neutrophil engraftment was achieved in 32 patients (97%) at a median of 15 days in LET group and 64 patients (97%) at a median of 14.5 days in non-LET group (P=0.243). Furthermore, platelet engraftment was achieved in 26 patients (79%) at a median of 34 days in LET group and 57 patients (86%) at a median of 31 days in non-LET group (P=0.282). These findings suggest that LET does not affect engraftment. Interestingly, the length of hospitalization in the LET group was significantly shorter than that in non-LET group (the median, 59.5 days versus 71 days; P=0.0488), suggesting that LET suppresses CMV reactivation leading to early discharge. [Conclusion] To our best knowledge, this is the largest retrospective study about the efficacy of LET in PTCy-Haplo SCT. LET is effective for prevention of CMV reactivation in PTCy-haplo SCT. Further studies focused on the long term effect of LET prophylaxis in PTCy-haplo SCT, such as the incidence of relapse and chronic GVHD, is warranted. Figure 1 Figure 1. Disclosures Nakagawa: AbbVie GK: Research Funding; Takeda Pharmaceutical Company: Research Funding. Teshima: Gentium/Jazz Pharmaceuticals: Consultancy; Merck Sharp & Dohme: Membership on an entity's Board of Directors or advisory committees; Pfizer Inc.: Honoraria; Nippon Shinyaku Co., Ltd.: Research Funding; CHUGAI PHARMACEUTICAL CO., LTD.: Research Funding; Fuji pharma CO.,Ltd: Research Funding; Takeda Pharmaceutical Company: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis International AG: Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; TEIJIN PHARMA Limited: Research Funding; Astellas Pharma Inc.: Research Funding; Bristol Myers Squibb: Honoraria; Janssen Pharmaceutical K.K.: Other; Kyowa Kirin Co.,Ltd.: Honoraria, Research Funding; Sanofi S.A.: Research Funding.

Sustained Effect of First Line Sequential Therapy with Intensive Consolidation Chemotherapy and Allogeneic Hematopoietic Stem Cell Transplantation (ASCT) after Reduced Intensity Conditioning (RIC) for Patients with Acute Myeloblastic Leukemia (AML) in First Complete Remission (CR1).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3000-3000
Author(s):  
Didier Blaise ◽  
R. Tabrizi ◽  
C. Faucher ◽  
Mohamad Mohty ◽  
J.O. Bay ◽  
...  
Keyword(s):  
High Risk ◽  
Cumulative Incidence ◽  
Sequential Therapy ◽  
High Dose ◽  
Intensive Chemotherapy ◽  
Consolidation Chemotherapy ◽  
Hematopoietic Stem ◽  
Cell Counts ◽  
To Receive

Abstract We recently reported our experience using RIC prior to ASCT in pts with AML in CR1 (Blaise, Cancer, 2005). We have shown that RIC-based ASCT can be safely used in this setting after intensive consolidation chemotherapy. With a median follow-up of 18 months, disease control was high and was not related to a selection bias (Mohty, Leukemia, 2005). In the present analysis, we investigated if this control was maintained after a longer follow-up. Thirty-seven pts (age: 51 (range, 26–60)) with high risk clinical characteristics (n=26; 70%) (Age ≥ 50 (N=22, 59%); Associated severe comorbidity (N=10; 30%)) and/or poor risk leukemic features (n=24; 65%) (Poor Cytogenetics (N=13, 35%); failure of first induction course (N= 10, 27%); secondary leukemia (N= 4; 11%), High white blood cell counts(N= 5; 14%) or partial remission (N=1, 3%)) were included in this analysis. After CR1, all pts received a low dose cytarabine consolidation chemotherapy followed one month later by one course of high dose cytarabine (24 g/m²) and anthracycline (HIDAC). Pts were then scheduled to receive ASCT prepared with RIC (fludarabine (180 mg/m²), busulfan (8 mg/kg), Thymoglobulin (2.5 to 10 mg/kg)) followed with BMT (N=10 (28%) or PBSC (N=26 (72%)). However after treating the first pts, it becomes evident that this schedule was not associated prohibitory toxicity. All following pts were, thus, proposed to receive one month after HIDAC, one course of melphalan (140 mg/m²) (HDMEL) with auto-SCT followed after recovery by the allo-SCT. Overall, 21 pts received HIDAC only and 16 HIDAC and HDMEL. Median follow-up at time of abstract is 3 years (16 months–70 months). 15 pts experienced aGVHD (Grade 1: 7; Grade 2: 4; Grade 3–4: 4). The cumulative incidence of grade 2–4 aGVHD was 22% (9–35). 33 pts (90%) were evaluable for cGVHD: 10 and 14 pts presented a limited and extensive form respectively. The cumulative incidence of cGVHD was 65 % (50–80). Three deaths were attributed to non-relapse causes (AGVHD: 1; CGVHD: 2° (cumulative incidence of non-relapse death (NRD): 8% (95% CI: 0–17). In all, 8 pts relapsed at 5 months (2–19) (cumulative incidence: 22% (95% CI, 9–35). Relapse was clearly associated with the absence of cGVHD (cGVHD: 4 (4–12), no cGVHD 44% (12–76), p=.02) and at a lesser extent with the intensity of consolidation chemotherapy (HIDAC: 33% (13–53); HIDAC + AUTO; 6% (0–19%), p=.06). Twenty-six pts are still alive in CR1 for overall survival and leukemia-free survival (LFS) probability estimates at 4 years of 67 % (95%CI, 49–81%) and 68% (95%CI, 50–81%) respectively. When restricting the analysis to the 33 pts evaluable for cGVHD, cGVHD remained the only independent risk factor positively influencing LFS (cGVHD: 83% (59–74); no cGVHD (56% (27–81), p=.03). We conclude that RIC Allo-SCT preceded by adequate prior intensive chemotherapy might offer a relatively low NRD while exerting a sustained leukemia control even in high risk pts. The intensity of intensive chemotherapy needed for optimal will be assessed prospectively.

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