BK Virus (BKV) Associated Haemorrhagic Cystitis Is Associated with Graft Versus Host Disease (GVHD) and Significant Morbidity Post Haematopoietic Stem Cell Transplant (HSCT).

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3040-3040
Author(s):  
Alesia Abigael Hunt ◽  
Anjum Bashir Khan ◽  
Donal McLornan ◽  
Majid A Kazmi ◽  
Matthew Streetly ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Bk Virus ◽  
Haematopoietic Stem Cell ◽  
Control Group ◽  
Cell Transplant ◽  
Haemorrhagic Cystitis ◽  
Graft Versus Host ◽  
Grade Ii

Abstract Abstract 3040 The Polyomavirus hominis 1 BK virus (BKV) is a non-encapsulated DNA virus, which infects up to 90% of the world's population, and may reactivate at times of severe immunosuppression, including post haematopoietic stem cell transplantation (HSCT). The significance of BK virus reactivation post Haematopoietic Stem Cell Transplant (HSCT) remains unclear. We collected retrospective data on viruria, viraemia, haemorrhagic cystitis (HC) and acute/chronic graft versus host disease (a/cGVHD) in patients at our institution over the period 2006 to 2011. We compared with a multivariate matched control group of 38, who did not reactivate BK. The groups were matched for age, sex, donor source and conditioning regimen including use of Alemtuzumab. Global BK reactivation incidence was 32% (38/118) of allogeneic HSCT during this period. 73% (28/38) of those who reactivated received volunteer unrelated donor (VUD) grafts, and 50% (18/38) received Alemtuzumab. Patients were sub-divided into those with high grade viraemia (HGV, VL >104 copies/ml), 47% (18/38) or low grade viraemia (LGV, VL<104 copies/ml), 53% (20/38). HGV was present in 57% of VUD transplants and 20% of sibling recipients, compared to LGV in 29% of VUDs and 70% of siblings. HGV influenced 1 year EFS; 18% versus 55% in LGV. Median OS was 173 days in HGV versus 345 days in LGV. Cumulative mortality rate in the BK group was 71% (27/38) as compared to 55% (21/38) in the control group (not significant). Relapse related mortality in the BK group was 22% (6/27) versus 57% (12/21) in the control group, at a median follow up of 229 days (p=0.088), indicating the high incidence of non-relapse causes of mortality in the BK group. 79% (30/38) of patients reactivating BK developed aGVHD, including 83% (15/18) with HGV, compared to 57% (21/37) in the control group (p=0.039). The number of patients who developed grade II-IV aGVHD in the BK group was 30/38 (79%) and 11/37 (20%) in the control group (p <0.001), figure 1. In 33% of patients BK reactivation preceded aGVHD by a mean of 12 days. 84% (27/32) of patients developed cGVHD, compared to 30% (18/30) in control group (p=0.05). Moderate-severe (NIH grade) cGVHD was more prevalent in patients reactivating BK, compared to control group; 75% (24/32) versus 3% (1/30) (p<0.001), figure 2. This data suggests the association of BK with an increased incidence of acute and chronic GVHD, and significant morbidity. Notably 10 patients developed severe complications including grade 4 HC (5/10), obstructive hydronephrosis and bladder wall dysfunction requiring invasive intervention. 7/10 (70%) of these patients had HGV; 2 patients reactivated early, failed treatment, developed obstructive renal failure and died. These patients had an increased rate of mortality compared to the whole study group (p=0.005), and all failed to achieve an EFS of over 1 year. Of note, 8.5% of all allografts developed grade 4 HC and 90% of these subsequently died. BK reactivation strongly correlates with acute and chronic GVHD and an increase in non relapse mortality. Routine surveillance for BK with risk scoring may allow earlier detection and reduced morbidity of BK and GVHD. Further prospective studies are required to understand the impact of the reactivation of the virus. Figure 1: Cumulative Incidence of acute GVHD Grade II-IV: Figure 1:. Cumulative Incidence of acute GVHD Grade II-IV: p <0.001 Figure 2: Cumulative Incidence of chronic GVHD moderate-severe: Figure 2:. Cumulative Incidence of chronic GVHD moderate-severe: p <0.001 Disclosures: No relevant conflicts of interest to declare.

scholarly journals Management of BK virus-associated haemorrhagic cystitis in allogeneic stem cell transplant recipients

2021 ◽  
Vol 8 ◽  
pp. 204993612199137
Author(s):  
Aditya Jandial ◽  
Kundan Mishra ◽  
Rajeev Sandal ◽  
Kamal Kant Sahu
Keyword(s):  
Stem Cell ◽  
Platelet Rich Plasma ◽  
Severe Disease ◽  
Unmet Need ◽  
Bk Virus ◽  
Haematopoietic Stem Cell ◽  
Cellular Immunotherapy ◽  
Cell Transplant ◽  
Clotting Factors ◽  
Haemorrhagic Cystitis

BK virus (BKV)-related haemorrhagic cystitis (HC) is an important cause of morbidity following allogeneic haematopoietic stem cell transplantation (HSCT). The various risk factors include high-level BKV viruria and/or viremia, myeloablative conditioning, acute graft versus host disease (GVHD), cytomegalovirus viremia, and unrelated or HLA-mismatched donor. The presence of high plasma BK viral load and cytopenias have been implicated as important predictors for protracted disease course. These patients frequently require hospitalisation which may extend for several weeks. Supportive measures in the form of analgesics, intravenous hydration, bladder irrigation, and transfusion support remain the mainstay of management. Various drugs have been used with limited success in this setting. These include antiviral drugs, fluoroquinolones, leflunomide, growth factors, clotting factors, estrogens, and prostaglandins. The role of adoptive cellular immunotherapy has also been explored but lacks clinical validation. The strategies aimed at expediting urothelial repair like hyperbaric oxygen therapy (HBOT), intravesical fibrin glue and platelet-rich plasma (PRP) are emerging. Some patients with severe disease do require surgical intervention to relieve urinary obstruction. The frequent co-occurrence of acute GVHD and CMV disease further complicates the management in such patients. There is an unmet need for effective and evidence-based options for the prevention and management of this disease. Due to lack of robust data supported by randomised trials, the acceptability of the available guidelines to simplify the treatment is expected to be low. Despite the availability of various treatment options, the management of BKV-related HC in day-to-day practice continues to be a challenge. The aim of this article is to put forward an up-to-date review of the preventive and therapeutic strategies for BKV-related HC.

Cotransplantation of Mesenchymal Stem Cells Prompted Platelets Recovery in HLA-Haploidentical/Mismatched Blood and Marrow Transplantation: A Randomized Phase II Study.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3284-3284 ◽  
Author(s):  
Kai yan Liu ◽  
Xiao Jun Huang ◽  
Yu hong Chen ◽  
Huan Chen ◽  
Lan ping Xu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Graft Versus Host Disease ◽  
Cumulative Incidence ◽  
Acute Gvhd ◽  
Control Group ◽  
Study Group ◽  
Graft Versus Host ◽  
Matched Sibling ◽  
Grade Ii

Abstract Up to now, HSCT has remained the standard and effective therapy for many hematopoietic malignant diseases and some non-malignant hematopoietic diseases. The HLA-matched sibling is the best source of donors; however, such donors are available for only approximately 30% of patients, especially in P.R.China. Virtually almost everyone possesses at least one HLA-haploidentical family donor. However, the use of such donors has presented a major challenge due to graft-versus-host disease (GVHD) and graft rejection. Peking University established a new approach for HLA-mismatched/hapoidentical HSCT using G-CSF primed bone marrow plus G-CSF-mobilized peripheral blood stem cells without ex vivo T cell depletion after the patients were treated with a modified BU/CY2+ATG regimen. Although the result was comparable to that in HLA matched sibling donor transplantation, there are still have room to improve the hemapoeitic/immune reconstitution, reduce the incidence and grade of GVHD further. Mesenchymal stem cell (MSC) is a pluripotent stem cell, supports hematopoeitc progenitors in vitro and posses potent immunosuppressive properties. We hypothesized that cotransplantation of culture-expanded MSCs and hematopoietic stem cells (HSCs) could facilitate engraftment and lessen graft-versus-host disease (GVHD). A phase I study has assessed the safety of contransplantation of MSC, and then a randomized, open-label phase II trial had been conducted in our institution during 2007.6–2008.6. Total twenty-nine patients with leukemia in CR were enrolled in this trial and randomized into study (n=14) or control group (n=15). Three patients in the study group had been found ineligible after randomized: one had relapsed leukemia just before conditioning, another had HLA identical donor and the third one is too overweighed to be infused of enough MSC. The remaining received the G-CSF-mobilized BM and PB from the HLA-mismatched/hapoidentical donor as have been published. Patients in the study group were given culture-expanded MSCs intravenously (3.0–5.0 × 105/kg) from the same donor or health volunteer within 24 hours before infusion of G-BM and PB. Baseline demographic and disease characteristics were balanced between the two groups. MSC infusions were well tolerated, without any infusion-related adverse events. All patients but one in the control group had achieved sustained neutrophil recovery. The median times to neutrophil (absolute neutrophil count ≥0.5 × 109/L) engraftment were 11 days (range, 11–19 days) and 11.5 days (range, 10–23 days) in the study and control groups respectively (p=1.0). There were 2 patients in the control group dead before the platelets engraftment, the median times to platelet recovery (platelet count ≥20 × 109/L ) were 13 days(range 9–52 days) and 19 days (range 10–36 days) (P=0.18). The platelet engraftment was prompted in the study group as for the time to count ≥50 ×109/L (21 days vs 26.5 days, P=0.047). Acute GVHD was observed in 7/11 of patients in study group, 2 had grade I, 5 had grade II. The cumulative incidence of grade II to IV acute GVHD was 48.9%. One patient in the control group had engraftment failure and another was dead of infection on +22 days. Of the thirteen remaining patients, nine patients experienced acute GVHD, 2 had grade I, 6 had grade II and 1 had grade IV. The cumulative incidence of grade II to IV acute GVHD was 61.1%. Our study demonstrated that cotransplantation of culture-expanded MSCs from donor or health volunteer in HLA-haploidentical/mismatched HSCT is feasible and safe. It is seems that MSCs are capable of accelerating hematopoietic cell engraftment, especially for platelet. Further study should be done to reveal whether MSC could reduce the incidence of acute GVHD.

scholarly journals Acute and chronic graft versus host disease after hematopoietic stem cell transplant

JBMTCT ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. 53-66
Author(s):  
Vaneuza A. M. Funke ◽  
Maria Claudia Rodrigues Moreira ◽  
Afonso Celso Vigorito
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Cell Transplant ◽  
Primary Therapy ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host

Graft versus host disease is one of the main complications of Hematopoietic stem cell, in­volving about 50% to 80% of the patients. Acute GVHD clinical manifestations and therapy is discussed, as well as new NIH criteria for the diagnosis and classification of chronic GVHD. Therapy for both refractory chronic and acute GVHD is an important field of discussion once there is no superiority for the majority of the agents after primary therapy has failed. Hence, this review is meant to be a useful tool of consultation for clinicians who are dealing with this complex complication.

Haematopoietic stem cell transplantation

2015 ◽  
Author(s):  
Drew Provan ◽  
Trevor Baglin ◽  
Inderjeet Dokal ◽  
Johannes de Vos ◽  
Hassan Al-Sader
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Fungal Infections ◽  
Chronic Gvhd ◽  
Haematopoietic Stem Cell ◽  
Sinusoidal Obstruction Syndrome ◽  
Cell Transplant ◽  
Post Transplant

Haemopoietic stem cell transplantation (SCT) - Indications for haemopoietic SCT - Allogeneic SCT - Autologous STC - Investigations for BMT/PBSCT - Pretransplant investigation of donors - Bone marrow harvesting - Peripheral blood stem cell mobilization and harvesting - Microbiological screening for stem cell cryopreservation - Stem cell transplant conditioning regimens - Infusion of cryopreserved stem cells - Infusion of fresh non-cryopreserved stem cells - Blood product support for SCT - Graft-versus-host disease (GvHD) prophylaxis - Acute GvHD - Chronic GvHD - Veno-occlusive disease (syn. sinusoidal obstruction syndrome) - Invasive fungal infections and antifungal therapy - CMV prophylaxis and treatment - Post-transplant vaccination programme and foreign travel - Longer term effect post-transplant - Treatment of relapse post-allogeneic SCT - Discharge and follow-up

Steroid Refractory Acute and Chronic Graft Versus Host Disease (GVHD) - Response to Photophoresis+/− Rituximab.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5358-5358 ◽  
Author(s):  
Ramakrishnan Parameswaran ◽  
Maggie Sekeramayi ◽  
Kelly McCaul ◽  
Bill Bradfeldt
Keyword(s):  
Stem Cell ◽  
Acute Gvhd ◽  
Hemorrhagic Cystitis ◽  
Chronic Gvhd ◽  
Bk Virus ◽  
High Dose ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Gi Tract ◽  
Steroid Refractory

Abstract Acute GVHD is an important complication following hematopoeitic stem cell transplantation (HSCT), with significant attendant morbidity and mortality. High dose steroids remain the cornerstone of therapy. Steroid refractory GVHD carries a very poor prognosis. Various therapies are available for steroid refractory acute GVHD, but response is not uniform. Among the less intensive regimens, extracorporeal photopheresis (ECP) and rituximab, a chimeric humanized anti CD 20 monoclonal antibody have been shown to be useful in treating refractory acute and chronic GVHD. We describe 8 patients who developed GVHD following transplantation of HLA-identical stem cells, from siblings in 7 and from an unrelated donor in one. 2 patients had steroid refractory chronic GVHD of the liver, 3 patients had a refractory chronic GVHD of the skin and one had a steroid responsive restrictive pulmonary syndrome. Of the patients with skin GVHD, 2 had chronic scelrodermatous GVHD, which was of 20 years duration in one patient and 8 in the other. 2 patients had acute GVHD of the GI tract. The age range was 21– 53 years. All patients were in complete remission from their primary disease at the time of therapy for GVHD. 3 patients had a diagnosis of acute lymphoblasitc leukemia and 5 acute myeloid leukemia All had failed treatment with high dose steroids and/or tacrolimus and/or cellcept, and, one had also failed ATG therapy. Then therapy for refractory GVHD was initiated with rituximab in 3 patients and with photopheresis in 5. 7 patients received ECP. One patient with refractory chronic GVHD of the liver received rituximab alone in addition of steroids and tacrolimus. The patients with acute GVHD were treated with daily ECP for 10 days and then were weaned down to two procedures every 2 weeks. Patients with chronic GVHD received ECP 2 to 3 times a week for 6 weeks and were subsequently similarly weaned down. In the patients with acute GVHD of the GI tract complete responses occurred at 10 days in one patient and 45 days in the second as determined by complete cessation of diarrhea, cramps and nausea. Both patients with chronic GVHD of the liver achieved normalization of the serum bilirubin by 26 and 38 days after initiation of therapy. All patients tolerated successful taper of steroid therapy. The two patients with sclerodermatous GVHD have shown marked improvement in skin texture and range of motion at the involved joints. The patient with the pulmonary symptoms has shown complete normalization of pulmonary function. 5 patients were at risk of CMV reactivation, but failed to do so. One patient developed BK virus associated hemorrhagic cystitis that required therapy with cidofovir. There were 3 admissions for neutropenic fever, three for pneumonia and one each for gastroenteritis, HSV gingivostomatitis and line related sepsis. Two patients had line related thrombosis. None of the patients had relapse of their disease. 2 of the responders had an ECOG performance status 2, two of 3, one of 4 and four of &lt;/= 1 while being treated. All patients demonstrated improvement in functional status. ECP and rituximab is a well tolerated and effective modality for therapy of steroid refractory chronic and acute GVHD in both related and unrelated marrow stem cell transplant recipients.

Donor Type Impacts the Incidence of Severe Acute but Not Chronic Graft- Versus-Host Disease (GVHD) after Reduced Toxicity Conditioning and Allogeneic Stem Cell Transplantation (ASCT) for Treatment of AML/MDS.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2227-2227
Author(s):  
Ri ma M. Saliba ◽  
Krishna V. Komanduri ◽  
Ebru Koca ◽  
Amin M. Alousi ◽  
Sergio Giralt ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Myeloablative Conditioning ◽  
Donor Type ◽  
Grade Ii ◽  
Reduced Toxicity ◽  
Grade Iii

Abstract The use of reduced intensity conditioning has resulted in a significantly lower incidence of severe acute GVHD (aGVHD) compared with myeloablative conditioning. It is not known if reduced toxicity myeloablative conditioning has a similar impact. To answer this question, we evaluated the incidence of acute and chronic GVHD in a homogeneous group of AML/MDS patients treated with Fludarabine (Flu) and IV Busulfan (IVBu) between April 2001 and August 2005 at MD Anderson Cancer Center. METHODS: Retrospective analysis of all 195 consecutive AML/MDS patients (pts) who received conditioning with IVBu (130 mg/m2 for 4 days) and Flu (40 mg/m2 for 4 days) and allogeneic stem cell transplantation (ASCT). The cumulative incidence of GVHD was estimated considering disease progression or death in the absence of GVHD as competing risks. Cox’s proportional hazards regression analysis was used to compare the rates of GVHD. RESULTS: Median age at the time of transplantation was 46 years (12–65) with 4 pts being younger than 18 years. 45% of pts (n=93) were females and 47% (n=92) were in complete remission at the time of transplant. 55% (n=107) received a graft from a matched related donor (MRD), 38% (n=74) from a matched unrelated donor (MUD), and 7% (n=14) from a 1 Ag mismatched related or unrelated donor. Stem cell source was peripheral blood in 85% of recipients of a MRD graft and bone marrow in 88% of recipients of a MUD graft. The median number of CD34+ cells infused was 4.6 x 106/Kg (range 1.1–8.9) and 3.8 x106/Kg (range 0.2–13) in the two groups respectively. GVHD prophylaxis consisted of tacrolimus and mini-methotrexate. In addition, 29/74 recipients of a MUD graft received varying doses of pentostatin on a phase I/II clinical trial. Evaluation of GVHD was limited to pts who received a graft from a MRD or MUD and engrafted (n=179/181). With a median follow-up among survivors of 48 months (range 16–80), 100 day actuarial survival was similar in recipients of a MRD (96%) and MUD (93%) graft (p=0.3). A total of 50 pts (28%) developed grade II-IV and 15 pts (8%) grade III-IV aGVHD within 100 days after ASCT. Donor type was the most significant predictor of the incidence of grade II-IV aGVHD with a cumulative incidence of 18% (95% CI: 12–27) in recipients of a MRD graft and 38% (95% CI: 29–51) in recipients of a MUD graft (HR=0.4, p=0.001). Similarly the rate of grade III-IV aGVHD was significantly lower in recipients of a MRD graft (4% vs. 15%, HR=0.2, p=0.007). In contrast, donor type did not impact the incidence of chronic GVHD with a comparable cumulative incidence by 2 years in recipients of a MRD (53%, 95% CI: 44–63) and MUD graft (45%, 95% CI: 35–58), (HR=0.9, p=0.8). Similar results were observed when the comparison was restricted to de novo chronic GVHD (n=32). Use of peripheral blood stem cells was the only significant factor associated with a higher rate of chronic GVHD in recipients of a MRD graft (56% vs. 35%; HR=2.5, p=0.03). Female gender was associated with a significantly lower rate of chronic GVHD in recipients of a MUD graft (HR=0.4, p=0.006). There was no significant impact for age, percent donor chimerism at the time of engraftment, diagnosis (AML versus MDS), or donor/recipient CMV serostatus on the rate of grade II-IV aGVHD or chronic GVHD. CONCLUSION: The incidence of grade II-IV aGVHD is low following IVBuFlu conditioning and ASCT in AML/MDS patients. In this setting, donor type affects the incidence of acute but not chronic GVHD. Figure Figure

Conditioning with Fludarabine, Busulfan, and ATG Prior to Reduced-Intensity Allogeneic Stem Cell Transplant for CLL Is Associated with a Low Incidence of Acute Graft-Versus-Host Disease.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4568-4568
Author(s):  
Samantha M. Jaglowski ◽  
Diane Scholl ◽  
Patrick Elder ◽  
Thomas S. Lin ◽  
John C. Byrd ◽  
...  
Keyword(s):  
Stem Cell ◽  
Graft Versus Host Disease ◽  
Stem Cell Transplant ◽  
Chronic Gvhd ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
Graft Versus Host ◽  
Significant Difference ◽  
Reduced Intensity ◽  
Count Recovery

Abstract Abstract 4568 Introduction: Allogeneic stem cell transplant (SCT) is the only potentially curative treatment available for CLL. While transplant-related mortality has decreased with use of reduced-intensity conditioning (RIC) regimens, acute and chronic graft-versus-host-disease (GVHD) remain important causes of morbidity and mortality, with up to 50% of patients developing chronic GVHD (cGVHD). While the optimal way to combat this has not been established, in vitro T cell depletion with ATG or alemtuzumab has been employed to attempt to lessen its incidence. Herein, we report our institutional experience with each of these agents. Patients and methods: Information on all patients who underwent RIC allogeneic SCT at Ohio State from January 1, 2002 to June 29, 2010 was obtained following approval from the ORRP. Data collected by the transplant coordinators was correlated with data in our electronic databases. Comparative statistics were performed using the Fisher exact test and all p-values are two-sided. Results: Between January 1, 2002 and June 29, 2010, 50 patients with CLL/SLL underwent RIC allogeneic SCT at Ohio State. Pretransplant characteristics are listed in Table 1. Thirty patients received fludarabine, busulfan, and ATG (FBA) as a preparative regimen, and 8 patients received alemtuzumab, fludarabine, and TBI (Cam/Flu/TBI). Another 6 patients received fludarabine and busulfan, 4 received fludarabine and cyclophosphamide, one received pentostatin, fludarabine, and ATG, and the patient who had a cord blood transplant received fludarabine, cyclophosphamide, TBI, and ATG. The breakdown of characteristics between patients who received FBA and Cam/Flu/TBI is also provided in Table 1. None of the characteristics were statistically different. Time to count recovery is provided in Table 2. There was not a statistically significant difference in the time to count recovery between FBA and Cam/Flu/TBI. Patients who received Cam/Flu/TBI received significantly more DLIs; patients who received FBA have not required any DLIs. Incidence of acute and chronic GVHD is provided in Table 3. There was not a statistically significant difference in rates or grades of aGVHD, but patients who received Cam/Flu/TBI were more likely to develop extensive cGVHD. Conclusions: While patients who received Cam/Flu/TBI were more likely to receive DLI, these were all done to treat disease recurrence, reflecting changes in group practice over time. There were no failures to engraft with FBA, and while not statistically significant in comparison to Cam/Flu/TBI, only 10% of patients developed grade 3 or 4 aGVHD. All of the patients who received Cam/Flu/TBI and developed cGVHD developed extensive disease. While the Cam/Flu/TBI sample is small, the FBA patients appear to fare no worse in terms of count recovery and development of GVHD without exposure to TBI, and this has become our institutional practice for patients with CLL. Disclosures: Lin: GlaxoSmithKline: Consultancy, Employment.

Low Dose Azacitidine (AZA) Reduces the Incidence of Chronic Graft-Versus-Host Disease (cGVHD) After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 742-742 ◽  
Author(s):  
Marcos de Lima ◽  
Simrit Parmar ◽  
Julianne J Chen ◽  
Sergio A Giralt ◽  
Gabriela Rondon ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Low Dose ◽  
Control Group ◽  
Cell Transplant ◽  
Off Label Use ◽  
Landmark Analysis ◽  
Off Label ◽  
Label Use

Abstract Abstract 742 AZA has immunomodulatory properties that may affect donor lymphocytes favorably, potentially leading to less GVHD after HSCT. We have been investigating low-dose AZA (32 mg/m2 daily for 5 days) to prevent AML/MDS relapse after HSCT. Interestingly, in our dose finding phase I study (Cancer, 2010) there was a suggestion of less cGVHD with longer AZA treatments. We then hypothesized that this approach leads to less cGVHD, and performed a comparison of patients that received AZA to prevent relapse versus historic controls that did not receive the drug. Major objective of this analysis is to determine the cumulative incidence of cGVHD with versus without AZA. Methods. Patients received AZA based on high risk of relapse disease, starting at a median of 45 days from transplant (range, 17–149). AZA effect on aGVHD was not studied since the drug was started after most cases of aGVHD had already occurred or/and had resolved or improved. Patients with active acute GVHD (aGVHD) were not eligible to receive AZA. Median dose was 32 mg/m2 (range, 8–40). Median number of AZA cycles was 3 (range, 1–54), and median time on AZA for patients that received >3 cycles (n=37) was 144 days (range, 93–1329). Using a computer algorithm, we randomly selected from our departmental database a control group consisting of patients who had received HSCT within the same time period, and had similar GVHD prophylaxis, stem cell source, and comparable low risk of grade II-IV aGVHD (Table). Two hundred and thirty patients were identified fulfilling these criteria. The rate of cGVHD was compared between the AZA group (grouped as 1–3 cycles and >3 cycles) and the control group, in a landmark analysis starting at 6 months after HSCT. Leukemia relapse or death in remission before cGVHD onset were considered as competing risks in this analysis. Results. Median follow-up was 25 months (range, 1–99) in the AZA group, and 31 months (range, 1.5–117) in the control group. 29, 24, and 115 patients in the >3 AZA cycles, 1–3 AZA cycles, and the control group were evaluable for the 6-month landmark analysis, respectively. The numbers of patients developing cGVHD and the HR at 2 years in this analysis were as follows: 53 of 115 controls (reference group), 11 of 24 patients who received 1–3 AZA cycles (HR at 2 years, 0.9; P=NS), and 6 of 29 patients who received >3 AZA cycles (HR at 2 years, 0.4; 95% confidence interval (CI), 0.1–0.8; P=0.02) developed cGVHD. Similarly, in a landmark analysis, the cumulative incidence of cGVHD was significantly lower in the subgroup that received >3 AZA cycles (figure). Conclusion. Low-dose AZA appears to reduce the likelihood of developing cGVHD. We are investigating if this effect is associated with preservation or improvement of the graft-versus-leukemia effect in an ongoing, randomized study. Disclosures: de Lima: Celgene: Research Funding. Off Label Use: azacitidine: off-label use as maintenance therapy following allogeneic stem cell transplant for MDS/AML. garcia Manero:celgene: Research Funding.

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