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.

High Dose Chemotherapy Using Beam without Autologous Rescue Followed by Reduced Intensity Conditioning Allogeneic Stem Cell Transplantation for Refractory or Relapsing Lymphomas - A Comparison of Delayed Versus Immediate Transplantation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5352-5352
Author(s):  
Andreas S. Buser ◽  
Martin Stern ◽  
Christoph Bucher ◽  
Caroline Arber ◽  
Dominik Heim ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Gvhd ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Reduced Intensity Conditioning ◽  
Cohort Group ◽  
Group A ◽  
Group B ◽  
Reduced Intensity

Abstract Patients with refractory/relapsing lymphoma are rarely cured by chemotherapy, so that allogeneic Hematopoietic Stem Cell Transplantation (HSCT) is often considered as an alternative despite being associated with substantial mortality. Reduced intensity conditioning (RIC) HSCT can induce a graft-vs-lymphoma (GvL) effect but relapse rate is high in advanced disease. High dose chemotherapy (HDC) for tumor debulking given before RIC HSCT has been advocated as a concept. We prospectively compared in a single center two sequential strategies in patients with refractory or relapsing lymphoma: a first cohort (group A) received BEAM chemotherapy without autologous stem cell support followed by delayed RIC HSCT at day 28. The second cohort (group B) received BEAM followed immediately by RIC HSCT. RIC HSCT was based on fludarabine 3×25 mg/m2 followed by 200 cGy TBI. Pretransplant characteristics were comparable in the two groups: group A included 10 patients, 7m/3f, median age 51 years (range 25–63) with 2 CLL, 3 follicular lymphomas (FL), 1 DLBCL, 2 Hodgkin lymphomas and 2 other B-cell lymphomas. Group B included 11 patients, 5m/6f, median age 48 years (range 31–59) with 4 CLL, 3 FL, 2 DLBCL, and 2 other lymphomas. Donors were HLA identical siblings (8 and 9 in group A and B) or unrelated donors (2 in each group). Three patients died before day 100 in group A (all from acute GvHD), whereas none died in group B. Non-hematological toxicity of the regimen before engraftment was comparable, only gut toxicity was higher in group B. As expected, days in aplasia (36 vs 12 days; A vs B; p< 0.001), days on antibiotics (61 vs 26 days; p =0.016) and length of hospital stay (36 vs 63 days; p =0.017) were significantly different. Cumulative incidence of acute GvHD ≥ grade II (90% vs 36% p= 0.01) and incidence of cGVHD (7/7 vs 6/11, p= 0.03) was higher in group A; hence we failed to show an advantage of separating RIC HSCT from the cytokine storm induced by BEAM. At last follow up, 7/10 patients in group A (median follow up 51 months) were alive, 6 of them in CR, 1 relapsed 9 months after RIC HSCT. In group B (median follow up 20 months), 9/11 patients were alive, 7 of them in CR, 1 in PR and 1 with no change. The two deaths in group B were related to cGvHD. No significant difference in 3 year overall survival (70% ±14% vs. 76%±14%, p= 0.53) was seen. These data challenge the initial concept of debulking first and delaying allogeneic RIC HSCT. They demonstrate encouraging tumor response and acceptable toxicity in patients with relapsing or refractory lymphoma. We confirm that allogeneic HSCT is a valid alternative for patients with resistant/relapsed lymphoma. These patients should be considered candidates for allogeneic HSCT earlier in the course of their disease and direct standard full conditioning with BEAM should be considered.

scholarly journals Intravenous Immunoglobulin Post Allogeneic Stem Cell Transplantation Is Associated with Lower Levels of CMV Reactivation

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2482-2482
Author(s):  
Costas K Yannakou ◽  
Aaron J Robinson ◽  
Sumita Ratnasingam ◽  
Andrew Boon Ming Lim ◽  
Yvonne Panek-Hudson ◽  
...  
Keyword(s):  
Stem Cell ◽  
Viral Load ◽  
Stem Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Time Of Death ◽  
Cmv Infection ◽  
Group A ◽  
Group B ◽  
Cmv Reactivation ◽  
Donor Source

Abstract Introduction Cytomegalovirus (CMV) reactivation is a common complication of allogeneic stem cell transplantation (ASCT), particularly within the first 100 days after stem cell infusion (D+100). It results in significant cost, morbidity and potentially mortality in the case of severe CMV disease. Intravenous polyvalent immunoglobulin (IVIg) has been used to support immunoglobulin levels post-ASCT in an attempt to reduce opportunistic infection and graft versus host disease (GVHD). Historically we employed routine IVIg therapy (0.5g/kg weekly for the first 12 weeks) as standard post-ASCT care. In July 2012 funding was withdrawn for IVIg for this indication. Since 2001 we have been using weekly quantitative polymerase chain reaction (PCR) analysis to monitor for CMV reactivation during the first 100 days after ASCT. We investigated whether the omission of post-ASCT IVIg altered the rate or consequences of CMV reactivation in the immediate post-ASCT setting. Methods We analysed sequential ASCT recipients from 2010 to 2014 and identified 100 patients who met the predetermined eligibility criteria. These subjects were then divided into two uniformly treated populations: ASCT recipients who either received (Group A, n=50) or did not receive (Group B, n=50) IVIg as part of their post-ASCT care. Inclusion criteria: matched adult unrelated or sibling donor source, age ≥18 years and CMV positive recipient by serology within 3 months prior to ASCT or CMV positive donor by serology. Exclusion criteria: CMV negative donor and recipient (D-/R-), umbilical cord donor source, death before day 100 or incomplete data available for analysis. CMV reactivation was defined as any detectable level by quantitative CMV PCR in the peripheral blood. The lower limit of detection for the assay was 20 copies/mL. A plasma CMV viral load of ≥400 copies/mL resulted in treatment with intravenous ganciclovir (5mg/kg twice daily) which was continued for a minimum of 2 weeks and was thereafter guided by weekly CMV viral load response. Patients with a CMV viral load of <400 copies/mL were observed with no specific treatment. CMV reactivation was recorded as minor (not requiring ganciclovir treatment) if CMV viral load remained <400 copies/mL and as major (requiring treatment) if CMV viral load reached ≥400 copies/mL within a single episode of infection. Time to first CMV reactivation and cumulative days of major CMV reactivation were also recorded. Results A total of 169 consecutive subjects were screened for study entry. Abstract 2482. Table 1:Cohort compositionsTotal screenedD-/R-Death <D+100Umbilical cord donorIncomplete dataTotal includedGroup A (IVIg)84206*8050Group B (non-IVIg)85215#8150 *: 1 subject had active CMV infection at time of death #: 2 subjects had active CMV infection at time of death Demographics were similar between Group A and Group B in terms of age (median 51.0 vs 48.5 years), sex (male: 33 vs 29) and transplant indication (acute leukaemia/MDS 28 vs 28; lymphoma 11 vs 11) and D+/R- transplants (9 vs 11). Comparing Group A and Group B, the number of subjects who had a CMV reactivation was 37 vs 39 and for minor reactivations the number was 28 vs 25. The median time to CMV infection was likewise similar: D+38 vs D+35. The number of patients with a major reactivation, however, was significantly different between Group A and Group B (13 vs 25 – RR 0.52, 95% CI [0.30-0.90], p 0.018), as was the cumulative number of days of major reactivation (181 vs 604 – RR 0.30, 95% CI [0.25-0.35], p <0.0001). The median number of days of major reactivation per patient was 13 vs 21 respectively. Conclusion Routine IVIg use in the immediate post-ASCT period did not reduce the rate or latency of CMV reactivation but was associated with a lower magnitude of CMV reactivation and a reduced requirement for anti-CMV therapy. These findings suggest that the use of IVIg post-ASCT may assist in reducing CMV viral burden. Disclosures No relevant conflicts of interest to declare.

Cytomegalovirus Reactivation and Relapse Following Allogeneic Stem Cell Transplantation Using a Reduced Intensity Conditioning Regimen.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5104-5104
Author(s):  
Revati Rao ◽  
Kevin Chin ◽  
Geoff Chan ◽  
Kellie Sprague ◽  
Andreas Klein ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Antiviral Therapy ◽  
Allogeneic Stem Cell Transplantation ◽  
Chronic Gvhd ◽  
Attributable Mortality ◽  
Reduced Intensity Conditioning ◽  
Cmv Reactivation ◽  
Reduced Intensity

Abstract Background: Recent studies have reported CMV reactivation rates of 42% to 65% in patients treated with allogeneic stem cell transplantation using reduced intensity conditioning regimens (RIT). However, published data on RIT patients who experience CMV reactivation, are treated successfully with antiviral therapy to eliminate detection, and who subsequently develop CMV relapse, is sparse. Methods: We performed a retrospective cohort analysis of 106 patients who underwent RIT at Tufts-New England Medical Center using a preparative regimen of pentostatin, extracorporeal photophoresis, and reduced total body irradiation, from 1997–2003. All patients received identical graft-versus-host disease (GVHD) prophylaxis, which consisted of IV cyclosporine and PO methotrexate. CMV serostatus was determined on all patients prior to transplant. All patients were screened weekly by CMV antigen capture assay after day +14. Patients did not receive CMV prophylaxis. CMV reactivation was defined as 2 consecutive positive (>2.1 pg/mL) CMV DNA measurements. CMV reactivation was treated with either Ganciclovir 5mg/kg IV daily or Valganciclovir 450mg PO BID until whole blood CMV DNA levels were no longer detectable. Patients were treated with antiviral therapy until a documented negative CMV DNA assay. Those found to have detectable CMV DNA after adequate therapy were then defined as having CMV relapse. Patients were also assessed for incidence of GVHD and mortality. Attributable mortality was defined as mortality in patients who had CMV relapse compared to those who had CMV reactivation without relapse. Fisher’s exact test was used to compare proportions, Kruskal-Wallis was used to compare means, and survival and time to reactivation and relapse were analyzed by Kaplan-Meier Results: Of 106 patients, 49 (46.2%) were CMV seropositive prior to transplant. Twenty -five (51%) of forty-nine CMV positive patients developed CMV reactivation at a median of 43 days (range 26 – 312 days) after receiving stem cells. Among patients with CMV reactivation, 36 were MRD and 13 were MUD. Nine (36%) of 25 patients with CMV reactivation developed CMV relapse. CMV relapse occurred at a median of 16 days (range 4 – 77 days) after CMV reactivation. CMV reactivation occurred earlier among those who relapsed (median 34 days, range 26 – 70 days) compared to those who did not relapse (median 55.5 days, 27 – 312 days, p=.03). Peak viral load was significantly higher in CMV relapsers (median 55.3 pg/mL, range 14.5 to 486.8) compared to non–relapse patients (median 4.4 pg/mL, range 2.1 – 58.2, p=. 0007). There was no difference in acute GVHD in the groups (100% vs. 75%, p=.26). However, those who did relapse had a higher incidence of chronic GVHD than those who did not (89% vs. 38%, p=.03). There was no difference in median survival between non-relapse and relapse patients (13 months vs. 16 months, p=. 99). The attributable mortality rate due to CMV relapse was 23%. Conclusions: Our results suggest there is a subgroup of patients who are at high risk for CMV relapse in the post RIT setting. Risks for CMV relapse include early reactivation and higher peak CMV viral loads. In addition, there was a higher risk of chronic GVHD in CMV relapse patients. We have identified a high- risk subset of patients who reactivate CMV for whom additional therapeutic strategies may be warranted.

Transplant Donor KIR Genotype Influences the Rate of CMV Reactivation Following T-Replete Stem Cell Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 188-188 ◽  
Author(s):  
Mark Cook ◽  
David C. Briggs ◽  
Charles F. Craddock ◽  
Premini Mahendra ◽  
Donald Milligan ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Myeloablative Conditioning ◽  
Kir Genes ◽  
Group A ◽  
Group B ◽  
Cmv Reactivation ◽  
Haplotype A

Abstract Background CMV reactivation is the commonest viral complication following allogeneic stem cell transplantation (SCT) and is a direct consequence of immunodeficiency. Natural killer (NK) and T-cells are the primary effector populations that suppress CMV replication. Killer immunoglobulin-like receptors (KIRs) are expressed on the surface of NK cells and T-cell subsets. Inhibitory KIRs have specificity for defined alleles of class I HLA and deliver an inhibitory signal to the cell. Activating KIRs bind weakly to HLA molecules and their true ligands remain unknown. KIR genes are polymorphic. Two broad haplotypes exist which differ in the number of activatory KIR genes that they contain. Haplotype A has 1 activatory KIR gene whereas haplotype B contains additional activatory genes. Methods We studied 107 patients undergoing allogeneic SCT at 3 UK Institutions to evaluate the effect of activating KIRs on CMV reactivation. Two thirds received standard myeloablative conditioning with TBI/Cy or Bu/Cy. One third received non-myeloablative conditioning. Recipient/donor CMV sero-status was determined by ELISA. Reactivation was defined as two successive PCR assays detecting >400 copies/ml. KIR genotyping was performed by PCR-SSP. Results In CMV seropositive recipients, the CMV reactivation rate was 50% in transplants from sibling donors and 64% in transplants from unrelated or HLA non-identical donors. In sibling transplants where both donor and recipient were CMV seropositive and the donor was homozygous for KIR Haplotype A (group A) the CMV reactivation rate was 65% .In contrast if the donor possessed at least one KIR haplotype B (group B) the reactivation rate was reduced to 27.5% (p=0.014). The protective effect of group B donors was seen only in patients who received a myeloablative non-T-depleted transplant. Here, the reactivation rate was 70.6% (12 from 17) when transplanted from a group A donor compared with 23.8% (5 from 21) when transplanted from a group B donor (p=0.0039). If a group B donor was used no reactivation was seen after 41 days, whereas in transplants from group A donors the risk of reactivation continued until day 100 (figure 1,p=0.018). The donor KIR genotype did not influence CMV reactivation rates in patients who received T-depleted grafts from sibling, unrelated or haploidentical donors. Conclusion In T-cell replete sibling donor transplants the use of a donor with multiple activating KIRs significantly reduces the risk of CMV reactivation when both donor and recipient are CMV seropositive. This is the first direct evidence of activating KIRs exerting a controlling effect on CMV in humans.

Improved Outcome Following Reduced Intensity Allogeneic Transplantation in Hodgkin’s Lymphoma Relapsing Post-Autologous Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 657-657 ◽  
Author(s):  
Kirsty J. Thomson ◽  
Karl S. Peggs ◽  
Paul Smith ◽  
Raj Chopra ◽  
Jim Cavet ◽  
...  
Keyword(s):  
Overall Survival ◽  
Hodgkin’S Lymphoma ◽  
Autologous Transplantation ◽  
Allogeneic Transplantation ◽  
Hodgkin's Lymphoma ◽  
Reduced Intensity Conditioning ◽  
Actuarial Survival ◽  
Group A ◽  
Group B ◽  
Reduced Intensity

Abstract Hodgkin’s Lymphoma is curable with primary therapy in the majority of patients. For those with relapsed or refractory disease, salvage with high dose chemotherapy plus autologous stem cell rescue is effective for a significant proportion. Patients relapsing following autologous stem cell transplantation, however, have an extremely poor prognosis. Allogeneic transplantation with conventional conditioning has proved excessively toxic in this setting, and reduced intensity conditioning has therefore been introduced, with encouraging preliminary results. This is a study of 72 patients relapsing following autologous transplantation, analysed in 2 groups. One group (A: n=38) then underwent allogeneic transplantation with reduced intensity conditioning at 6 UK centres (1998–2004), with alemtuzumab 100mg, fludarabine 150mg/m2 and melphalan 140mg/m2. Donors were HLA-matched related in 63% of cases, and unrelated in the remaining 37%. The second group (B: n=34) is a control cohort, who relapsed before the advent of reduced intensity conditioning, and were treated with chemotherapy +/− radiotherapy alone. The groups were equivalent in age (median- A 31yrs [20–51]; B 29yrs [13–47]), disease subtype (&gt;85% nodular sclerosing both groups), time from diagnosis to autograft (median-A 18mo [7–139]; B 20mo [4–185]), and lines of prior therapy pre-autograft (median 3 both groups). Median time from autograft to relapse for group A was 13mo (2–56) and for group B 10mo (3–40), and patients were only selected for inclusion in group B if they responded to further salvage therapy, attained at least a stable response to treatment, and lived for &gt;12 months following relapse (median time from relapse to allogeneic transplant for group A is &lt;12 months). In this way, it was intended to include only those patients who would have been eligible for reduced intensity allogeneic transplantation had this been available at the time. Indeed, the entry criteria for group A were arguably less stringent, as patients with chemorefractory disease were included (n=14, 37%). Overall survival from diagnosis was significantly better in group A, with actuarial survival at 10yrs of 48% compared to 15% in group B (p=0.0014), and overall survival from autograft was 65% at 5 yrs in group A and 15% in group B (p=&lt;0.0001). Of group B patients treated with chemotherapy/RT alone, only 2/34 patients remain alive at a median follow-up of 22 months from relapse, one of whom has progressive disease. For group A receiving reduced intensity transplantation, actuarial survival from the time of allograft was 50% at 5 yrs. In the chemoresponsive patients, OS at 5yrs was 57% at 5 yrs with current progression-free survival of 39% at 5 yrs. This demonstration of the potential efficacy of reduced intensity transplantation in a group of heavily pre-treated patients who have failed autograft and whose outlook is otherwise extremely poor, strongly suggests further studies of reduced intensity allogeneic transplantation in Hodgkin’s Lymphoma are warranted.

Prognostic Factors for CMV Reactivation/Infection after Stem Cell Transplantation and Value of Oral Valganciclovir for Preemptive Therapy.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5369-5369
Author(s):  
Thorsten Graef ◽  
Tatjana Bobrikova ◽  
Ortwin Adams ◽  
Roland Fenk ◽  
Leilani Ruf ◽  
...  
Keyword(s):  
Stem Cell ◽  
Prognostic Factors ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Therapeutic Response ◽  
Preemptive Therapy ◽  
Cmv Infection ◽  
Oral Valganciclovir ◽  
Cmv Disease ◽  
Cmv Reactivation

Abstract INTRODUCTION: Cytomegalovirus (CMV) infection and disease are major complications of allogeneic stem cell transplantation (SCT). Different strategies have been developed to reduce the risk for CMV-associated disease and death. Before routine use of prophylactic regimens, CMV seropositive allogeneic HCT recipients had a 70 to 80 percent risk of reactivation of this virus, and one-third of these patients developed CMV disease. Preemptive antiviral therapy has markedly reduced the incidence and severity of CMV disease, but in spite of these advances significant morbidity and mortality are associated with CMV. PATIENTS AND METHODS: In this unicenter retrospective study, we studied 197 adults who received allogeneic HSCT mostly because of myeloid leukaemia between 2000 and 2004. The median age was 46 years (range, 17-68), included were 80 female and 117 male patients. The grafts consisted mainly of PBSC (94%) and in 54% unrelated donors were used. Conditioning regimens included TBI in 42% cases. The CMV-serostatus proportions were D-/P- 34%, D-/P+ 20%, D+/P- 14% and D+/P+ 32%. All patients with ablative regimens received prophylactic i.v. acyclovir starting one day after SCT. After discharge oral CMV-prophylaxis consisted of famciclovir (52%), acyclovir (30%), valacyclovir (8%) or ganciclovir (10%). The prognostic factors for CMV reactivation in recipients were assessed by univariate analyses and Pearson correlations. RESULTS: CMV seropositive recipients (p=.00001) and donors (p=.03) were significantly associated with a higher rate of CMV reactivations, and also the use of an unrelated donor was a prognostic factor for more frequent CMV reactivations (p=.007). TBI, age and GvHD were not associated with more frequent of CMV reactivations. Famciclovir and acyclovir were associated (p=.0001) with a higher rate of CMV-reactivations in CMV+ recipients, than valacyclovir or ganciclovir. In all, we observed 60 cases (31%) of CMV reactivation/infection (D-/P- 14%, D-/P+ 30%, D+/P- 7% and D+/P+ 49%) after a median of 50 days (range, 9-403). 48 of them (80%) were CMV+ before SCT and 50 of 60 (83%) were successfully treated. In all, 30 patients (7 CMV-, 23 CMV+) were treated with valganciclovir and 30 (5 CMV-, 25 CMV+) received other agents (valacyclovir n=11, foscarnet n=4 or ganciclovir n=15) after a single dose of i.v. IG. 29 of 30 patients who received valganciclovir had a negative PCR result, confirmed by 2 consecutive CMV-PCRs, after a median of 24 days (range, 9 – 365). In the group of the CMV+ recipients, valganciclovir resulted in a statistically superior therapeutic response (p=0.024) when compared to other agents. Oral valganciclovir therapy was well tolerated and toxicity was limitted to manageable cytopenia. 11 of 12 CMV- recipients (91%) were also successfully treated after CMV-infection, with no significant difference between the different therapeutic agents. CONCLUSION: CMV seropositive recipient is the primary prognostic factors for CMV reactivation after allogeneic SCT. The prophylactic use of valacyclovir and ganciclovir were significantly better in CMV+ recipients, than famciclovir or acyclovir. Valganciclovir resulted in a better therapeutic response in comparison to other agents after CMV reactivation and should be tested as primary preemptive therapy in randomized trials.

scholarly journals IMPACT OF PRETRANSPLANT DONOR AND RECIPIENT CYTOMEGALOVIRUS SEROSTATUS ON OUTCOME FOR MULTIPLE MYELOMA PATIENTS UNDERGOING REDUCED INTENSITY CONDITIONING ALLOGENEIC STEM CELL TRANSPLANTATION.

2013 ◽  
Vol 5 (1) ◽  
pp. e2013026 ◽  
Author(s):  
Jean Elcheikh
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cumulative Incidence ◽  
Acute Gvhd ◽  
Reduced Intensity Conditioning ◽  
Grade Ii ◽  
Cmv Reactivation ◽  
Reduced Intensity

To investigate the impact of pre-transplant CMV serostatus of donor or recipient on outcome of patients undergoing allogeneic hematopoietic stem cell transplantation (Allo-SCT) for Multiple Myeloma (MM). To our knowledge no data are available in the literature about this issue.We retrospectively followed 99 consecutive patients who underwent reduced-intensity conditioning (RIC) Allo-SCT for MM in our cancer centre at Marseille between January 2000 and January 2012. Based upon CMV serostatus, patients were classified as low risk (donor [D]-/recipient [R]-) 17 patients (17.1%), intermediate risk (D+/R) 14 patients (14.1%), or high risk – either (D-/R+) 31 patients (31.3%) or (D+/R+), 37 patients (37.3%).Cumulative incidence of CMV reactivation was 39% with a median time of 61 days (26–318). Three patients (3%) developed CMV disease. Two factors were associated with CMV reactivation: CMV serostatus group (low: 0% vs intermediate: 29% vs high: 50%; p=0.001) and the presence of grade II–IV acute GvHD (Hazard Ratio: HR=2.1 [1.1–3.9]). Thirty-six of the 39 patients (92%) with CMV reactivation did not present positive detection of CMV after a 21-day median duration preemptive treatment with ganciclovir. Cumulative incidence of day 100 grade II–IV acute GvHD, 1-year chronic GvHD and day 100 transplantation related mortality (TRM) were 37%, 36% and 9%, respectively. CMV reactivation and serostatus were not associated with increased GvHD and TRM or short survival. Only the presence of acute GvHD as a time dependent variable was significantly associated with increased TRM (p=0.005). Two-year overall and progression free survival were 56% and 34%, respectively.Donor and recipient CMV serostatus and acute GvHD are independent factors for increased CMV reactivation in high-risk MM patients undergoing RIC Allo-SCT. However, we did not find any influence of CMV reactivation on post transplantation outcome. CMV monitoring and pre-emptive treatment strategy could in part explain these results. Novel prophylactic measures such as immunotherapy and drug prophylaxis need to be considered in this specific group of patients, warranting further prospective studies.

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