Risk Factors of GANCICLOVIR–RELATED Neutropenia After Allogeneic STEM CELL Transplantation: A Retrospective Monocenter Study On 547 Patients

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4186-4186
Author(s):  
Geoffroy Venton ◽  
Roberto Crocchiolo ◽  
Jean El-Cheikh ◽  
Sabine Furst ◽  
Angela Granata ◽  
...  
Keyword(s):  
Risk Factors ◽  
Bone Marrow ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Antiviral Therapy ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Cmv Reactivation ◽  
Related Mortality

Abstract Abstract 4186 Introduction: Cytomegalovirus (CMV) disease is a serious complication that may occur in the weeks or months following bone marrow transplantation. Therefore it must be treated as soon as positive CMV reactivation is noticed: pre-emptive therapy has demonstrated to improve survival among patients reactivating CMV after transplantation. However, GANCICLOVIR (GCV) as well as CMV infection itself involves a well-know marrow toxicity, notably neutropenia that may consequently expose these immunosuppressed patients to life-threatening bacterial and/or fungal infections. So far, only two studies specifically identified risk factors and outcome of GCV –related neutropenia, finding low marrow cellularity between day 21 and 28, hyperbilirubinemia > 6mg/dl during the first 20 days, serum creatinine > 2mg/l after day 21, and absolute neutrophil count as predictive factors. However, transplantation has evolved in recent years, especially thanks to the reduce intensity conditioning (RIC) and supportive care. The present analysis aims at identifying risk factors of neutropenia among a large cohort of patients treated by pre-emptive GCV who received allogeneic stem cell transplantation at our Institution over last years. Patients and Methods: This is a retrospective study on a cohort of 547 consecutive patients allografted from January 2005 to June 2011 at our Institution. Diagnoses were: acute myeloid and lymphoblastic leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, chronic lymphocytic leukemia, myeloproliferative and myelodisplasic syndromes, aplastic anemia, metastatic solid tumor. Transplants were performed using three sources: bone marrow, peripheral blood stem cells, cord blood; patients receiving haploidentical transplant were excluded. Donors were HLA-sibling and matched or mismatched unrelated ones. Myeloablative, non-myeloablative and RIC regiments were administered according to local guidelines or established protocols. The principal objective of the study was to identify factors associated with the occurrence of grade 3–4 neutropenia among patients receiving antiviral therapy due to CMV reactivation. Secondarily, overall survival (OS), transplant-related mortality (TRM) and relapse/progression were analyzed and compared between patients who reactivated CMV vs. those who did not. Results: A total of 547 patients were included in the analysis. One hundred ninety patients presented CMV reactivation (34.7%). Thirty patients were excluded from the analysis because they already had neutropenia at the time of reactivation. Finally one hundred and sixty patients were analyzed. We found that ANC above 3000 is a protective factor, (HR= 0.26, CI 95 %, 0.125–0.545, p < 0001); creatinine <2ml/dl after 21 days is a risk factor for GCV- related neutropenia (HR= 2.4, CI 95%, 1.11 – 5.17, p = 0.002) as well as a high viral load (HR=2.68, CI 95%, 1.25–5.737, p = 0.01). Using landmark analysis at day +100, overall survival (OS) at five years is lower for patients with CMV reactivation 43% (32–54) vs. 57% (46–68), p<0.0001. As concerns treatment-related mortality (TRM), we found a higher TRM among patients who developed CMV reactivation: 29% (21–36) vs. 12% (8–17), p=0.003. There is no significant difference in the risk of relapse in patients who reactivated CMV vs. those who did not reactivate 32 % vs. 34 % (p=n.s.). In conclusion, this large analysis revealed three risk factors of GCV-related neutropenia among patients with CMV reactivation after allogeneic hematopoietic stem cell transplantation; prompt identification of patients at risk when antiviral therapy is started may allow clinicians to adopt adequate preventive measures, thus potentially reducing morbidity and mortality associated with CMV reactivation. Disclosures: No relevant conflicts of interest to declare.

Parainfluenza virus infections after hematopoietic stem cell transplantation: risk factors, response to antiviral therapy, and effect on transplant outcome

Blood ◽  
2001 ◽  
Vol 98 (3) ◽  
pp. 573-578 ◽  
Author(s):  
W. Garrett Nichols ◽  
Lawrence Corey ◽  
Ted Gooley ◽  
Chris Davis ◽  
Michael Boeckh
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Antiviral Therapy ◽  
Cell Transplantation ◽  
Parainfluenza Virus ◽  
Hematopoietic Stem ◽  
Viral Shedding ◽  
Autologous Hsct ◽  
Related Mortality

Abstract Parainfluenza virus (PIV) infections may be significant causes of morbidity and mortality in patients undergoing stem cell transplantation, but data regarding their impact on transplant-related mortality is limited. This study sought to determine the risk factors of PIV acquisition and progression to lower respiratory tract infection, their impact on transplant-related mortality, and the effectiveness of antiviral therapy. A total of 3577 recipients of hematopoietic stem cell transplantation (HSCT) between 1990 and 1999 were studied. PIV infections occurred in 253 patients (7.1%); 78% of these infections were community acquired. Multivariable analysis identified the receipt of an unrelated transplant as the only risk factor for PIV acquisition; the dose of corticosteroids at the time of PIV infection acquisition was the primary factor associated with the development of PIV-3 pneumonia, both among allogeneic and autologous HSCT recipients. Both PIV-3 upper respiratory infection and pneumonia were associated with overall mortality. Pulmonary copathogens were isolated from 29 patients (53%) with pneumonia. Mortality was highly influenced by the presence of copathogens and the need for mechanical ventilation. Aerosolized ribavirin with or without intravenous immunoglobulin did not appear to alter mortality from PIV-3 pneumonia, nor did such therapy decrease the duration of viral shedding from the nasopharynx among patients with pneumonia. Corticosteroid administration thus drives the development of PIV pneumonia in a dose-dependent fashion, even among autologous HSCT recipients. Both upper and lower tract PIV infections are predictors of mortality after HSCT. Currently available antiviral therapy appears to be inadequate in reducing viral shedding or mortality once pneumonia is established.

Favourable Overall Survival with Myeloablative Allogeneic Stem Cell Transplantation for Follicular Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3005-3005
Author(s):  
John Kuruvilla ◽  
Qikun Bao ◽  
Erica Messner ◽  
Vikas Gupta ◽  
Thomas L. Kiss ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Follicular Lymphoma ◽  
Disease Control ◽  
Allogeneic Stem Cell Transplantation ◽  
Unrelated Donor ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract Introduction Allogeneic stem cell transplantation (Allo-SCT) remains an option for patients with follicular lymphoma (FL). Our program employs a strategy using allo-SCT for patients (pts) with high risk disease based on clinical characteristics. We performed a retrospective analysis to examine long-term disease control and treatment-related mortality. Methods 41 pts with indolent FL (follicular small cleaved [FSC], follicular mixed [FM] or FL grade 1,2 by WHO criteria) underwent allo-SCT at our institution between Jan 1989 and Dec 2005. Patients were in a chemosensitive remission at the time of SCT. The conditioning regimen consisted of busulfan (1 mg/kg PO q6h X4 days between 1989–200 and 3.2 mg/kg IV daily X 4days subsequently) and cyclophosphamide 60 mg/kg X 2 days. Cyclophosphamide 60 mg/kg X 2 days and TBI 12 Gy was used for unrelated donor SCT. GVHD prophylaxis was with cyclosporine A and methotrexate. Results There were 21 males and 20 females. The median age at the time of transplant was 45 years (range 24 to 58). Histologic subtype was: unclassified indolent FL: 3, Grade 1 or FSC: 17, Grade 2 or FM: 21. The median number of prior chemotherapy regimens was 2 (range 1 – 6) and was unavailable in 5. Prior anthracycline: 37, prior purine analog: 9, prior platinum-based: 20, prior auto-SCT: 1, prior rituximab: 11. The median time from diagnosis to allo-SCT was 23 months (range 6 – 161). 38 pts received BuCy conditioning. 2 patients underwent RIC SCT. Graft source was: matched related (MRD) bone marrow (BM): 28, MRD peripheral blood stem cells (PBSC): 4, Mismatch related (MMRD) bone marrow (BM): 1, MMRD PBSC: 2, matched unrelated donor (MUD) BM: 1, MUD PBSC: 1, and syngeneic BM: 4. The five year overall survival is 77% (95% confidence intervals 73 – 91%) with a median follow-up of 48 months post-SCT. Treatment-related mortality was 5 of 41 pts (12%). Non-relapse mortality was seen in one patient (3%). One patient has relapsed at over 3 years post-SCT while all recipients of syngeneic SCT remain in remission. Conclusions These results demonstrate that in selected patients, a fully myeloablative allo-SCT utilizing Busulfan-Cyclophosphamide conditioning provides excellent overall survival and disease control with low TRM. Prospective comparisons of RICSCT with myeloablative SCT should be performed in order to better evaluate these strategies.

An Alternative Method for Myeloablative Allogenic Stem Cell Transplantation in Hematological Malignancies: Reduced BUCY2 and GCS-F Primed Bone Marrow Stem Cells

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4138-4138
Author(s):  
Eucario León-Rodríguez ◽  
Patricia Guzmán-Uribe ◽  
Sandra Ileana Pérez-Álvarez ◽  
Andrea Castro-Sánchez ◽  
Karla Adriana Espinosa-Bautista ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Dose Reduction ◽  
Cell Transplantation ◽  
Neutrophil Count ◽  
Related Donor ◽  
Low Incidence ◽  
Related Mortality

Abstract Abstract 4138 Background: Allogeneic stem cell transplantation (ASCT) is the standard treatment for several diseases. However, the morbidity and mortality associated with the procedure limit its widespread use in developing countries. We implemented a novel conditioning method to reduce complications and improve survival. We hypothesized that the dose reduction in this regimen (about 20–25%), would preserve its myeloablative and immunosupressive effect, but with significantly reduced toxicity and mortality. Objectives: Describe clinical characteristics, toxicity, frequency of GVHD and survival of adult mexican patients undergoing ASCT using reduced BUCY2 and G-CSF primed bone marrow as a conditioning method. Material and Methods: Prospective cohort study of patients with matched related donor allotransplant using this new method from November 1999 to December 2011. Stem cell collection was obtained from iliac crests by multiple aspiration. The donor received GCS-F (10μg/kg/day) 3 to 5 days prior to harvest. The conditioning included: Busulfan 12mg/kg PO (3mg/kg/d in -7, -6, -5, -4), Cyclophosphamide 80mg/kg IV (40mg/kg/d in −3, −2), and GVHD prophylaxis with Cyclosporine A (1.5mg/kg bid, beginning at -1: target 200–300 ng/μL) and a short course of Methotrexate. All patients received antimicrobial prophylaxis once the neutrophil count reached < 500/μL. Weekly CMV antigenemia was performed until the 4th month post-transplant. Neutrophil and platelet engraftment were defined as the first of three consecutive days with a neutrophil count □ 0.5 × 109/L and □ 20 × 109/L without transfusion, respectively. Transplant related mortality was defined as any death directly attributed to the conditioning regimen, to aplasia during transplant and/or to infectious or GVHD complications. Engraftment failure was defined as the inability to achieve neutrophil and platelet engraftment during the first 28th days postransplant. Statistical Analysis: Descriptive analysis was used for continuous and categorical variables. Kaplan–Meier curves to asses overall survival, and central tendency measures to analyze: general features, time of engraftment and hospitalization days (SPSS 17.0). Results: 29 patients undergoing ASCT with reduced BUCY2 and GCS-F primed-bone marrow were included. All had a HLA-matched related donor, median age of 29 years. 19 patients (65.5%) were male. The diagnosis was: MDS in 10 patients (34.5%), CML in 9 (31%), ALL in 6 (20.7%), AML in 2 (6.9%) and PNH in 2 (6.9%). The median CD34+ transfused cells: 1.9 × 106/kg. Median time to neutrophil and platelet recovery: 20 days (range 14–29) and 15 days (range 7–36), respectively. All patients engrafted. The most common toxicity was mucositis (79.3%) with grade III-IV in 48.3% of cases. Hepatic (41.4%) and renal (48.3%) toxicities, were mild, transient and easily managed with support measures (table 1). Acute and chronic GVHD developed in 6.9% and 34.5% of patients, respectively. There was no mortality at 30 days, and 100-day mortality was 7% (2 patients), attributed to infectious complications. Transplant related mortality was 10% (3 patients) and 5-year overall survival was 70.3%. Discussion and conclusions: Our results show some advantages compared with standard regimens: noteworthy 5-year OS (70%), similar time to engraftment as for HSC from peripheral source and low GVHD incidence. There was a low TRM (10%), compared to myeloablative regimens, and probably lower than reduced intensity transplants. Main toxicities were grade II-III mucositis and hepatic toxicity, without serious clinical significance. Also, there was a low incidence of acute GVHD (6.9%) probably related to reduced tisular toxicity associated to the conditioning dose reduction, as well as the use of primed bone marrow. In conclusion, this strategy preserves an immunosuppressive and cytotoxic effect allowing eradication of the malignant clone with adequate bone marrow engraftment, acceptable toxicity, low incidence of GVHD and low TRM, representing a new alternative for ASCT. Disclosures: Armengol-Alonso: European Society of Clinical Oncology: Fellowship Other. Neme-Yunes:Agrupación Mexicana para el Estudio de la Hematología: Employment.

High Incidence but Low Morbitiy of Early Cytomegalovirus (CMV) Infections Following Reduced Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation with Alemtuzumab and Ganciclovir Prophylaxis.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5098-5098
Author(s):  
Renu Lamba ◽  
George Carrum ◽  
Robert Krance ◽  
Helen Heslop ◽  
Malcolm Brenner ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Great Promise ◽  
Post Transplant ◽  
High Incidence ◽  
Cmv Reactivation ◽  
Reduced Intensity

Abstract Background : IThe CD52 monoclonal antibody Alemtuzumab appears to be of great promise when incorporated as a lymphocyte depleting agent in RIC stem cell transplants. However the degree of functional immunosuppression produced by this antibody in this application has not yet been well characterized. As a surrogate functional marker, we have studied the incidence and pattern of CMV infection following RIC transplantation regimens with a regimen incorporating this antibody. Methods : We analyzed CMV infections and risk factors in 49 patients who underwent allogeneic stem cell transplantation with a RIC regimen consisting of Fludarabine (120mg/m2), total body irradiation (450 cGy), antithymocyte globulin (40mg/kg), (n=11) or Alemtuzumab (40mg), (n=38) with or without CD45 monoclonal antibodies for various malignant disorders. Donors were HLA identical (related, n=20; unrelated, n=20) or one antigen mismatched (n=9). Ganciclovir was used as prophylaxis starting at engraftment or on recovery from cytopenias. CMV antigenemia and polymerase chain reaction based assays were performed on peripheral blood twice a week till day 100 and then on each clinic visit. Results : The cumulative incidence of CMV reactivation at 1 year post-transplant with Alemtuzumab, in patients at risk, was 60% (95% CI, 45%–78%). Median time to reactivation of 24 days (range, 5– 95 days). Fifty seven percent (12/21) of the reactivations occurred before day 30. Recurrence of CMV reactivation occurred in 38% (8/21) of patients with a median number of recurrences of 2 (range, 1–6) and they extended beyond day 100. Only one patient developed CMV colitis and fully recovered with treatment. There was no CMV related mortality. The overall non-relapse mortality was 16% and overall survival in CMV reactivators and non-reactivators was not statistically different. Risk factors for CMV reactivation analyzed were patients age, sex, acute graft vs host disease, Alemtuzumab use, Ganciclovir use before day 30 and absolute lymphocyte count at day 30. In univariate analysis, use of Alemtuzumab (P= 0.001) and starting Ganciclovir after day 30 (P= 0.002) were significantly associated with CMV reactivation but in multivariate analysis only starting Ganciclovir after day 30 was statistically significant, P= 0.009 (95% CI, 1.5%–17%). Conclusions : RIC stem cell transplantation using Alemtuzumab is associated with a particularly high incidence of early CMV reactivation, and is also associated with recurrent reactivation extending beyond day 100. Although the incidence of CMV disease was low, the high frequency of viral reactivation with Alemtuzumab is likely an indicator of profound post transplant immune suppression, suggesting that despite the “reduced intensity” of the conditioning, these patients require early, comprehensive and prolonged pre-emptive/prophylactic therapy for opportunistic infections.

Prolongation of Post Relapse and Overall Survival in Patients with Multiple Myeloma by Salvage Strategy with the Combination of Thalidomide and Reduced Intensity Conditioning Allogeneic Stem Cell Transplantation Based on the Nature of Disease Progression after Autologous Bone Marrow Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3494-3494
Author(s):  
Izhar Hardan ◽  
Avichai Shimoni ◽  
Abraham Kneller ◽  
Abraham Avigdor ◽  
Noga Shemtov ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Reduced Intensity Conditioning ◽  
Duration Of Response ◽  
Reduced Intensity ◽  
Related Mortality

Abstract The impact of the use of autologous BMT (ABMT) as an up-front therapy on the natural history of multiple myeloma (MM) is limited, mainly due to the course of disease at progression after ABMT. Conventional salvage at that stage was reported to offer overall survival of only 14–17 months. The benefit of thalidomide and reduced intensity allogeneic stem cell transplantation (RIC SCT), which were introduced at that stage, is limited by the duration of response and toxicity. It was shown, however, that the aggressiveness of relapse clearly predicts for outcome in this set-up. Methods. Patients (pt’s) with progression after ABMT were treated according to a strategy based on the nature of relapse, with thalidomide (Thal) and reduced intensity conditioning allogeneic stem cell transplantation (RIC SCT) as following: all progressing patients had Thal ± Dexa for induction of response, but only at a clinical indication for therapy. DTPACE combination was given to those who failed to respond to Thal. Pt’s with aggressive progression were offered a RIC SCT at response, while patients with an indolent progression were offered a RIC SCT only at escape from response to Thal or if being resistant to Thal+Dexa. Re-induction therapy was delivered prior to transplant. The post transplant therapy included DLI and/or Thal according to the findings in minimal residual disease (MRD) studies and base line chromosomal studies. Results. Seventy five pts (age 36–66, median 58 y) with indolent (n= 46, 61%) or aggressive (n=29, 39%) progression, were treated according to this strategy. The overall response rate (= or &gt;PR) to Thal ± Dexa was 58.6%. Thirty six pt’s (48%) subsequently underwent RIC SCT (27 related, 9 unrelated donor) and 10 pts with an indication but no matched donor had a 2nd ABMT. Treatment related mortality was 9.3% (7 pt, all after RIC SCT, giving transplant related mortality rate of 16.6% for RIC SCT in this setting). RIC SCT reversed resistant to Thal in 7 pt. The median overall survival (OS) from progression of the entire group is 39 months with a projected 3-years survival rate of 52% (follow-up 19m-74m, median= 34m). The nature of relapse was found to be a strong independent favorable prognostic factor with a median post relapse OS of &gt;62m (not yet reached) vers. 24m, for pt’s with indolent compared with aggressive relapse (p=0.00002). In 24 patients (32%), the duration of response exceeded the first progression free period (from ABMT until progression). The median OS from ABMT of this group of patients is 85m, compared with a median OS rate of 56m from ABMT in a comparable historical group of 62 patients from our center that relapsed after ABMT prior to the introduction of the Thal /RIC SCT strategy. Conclusion. The therapy with Thal and RIC SCT with a strategy based on the nature of disease progression after ABMT can improve post relapse and overall survival of MM patients. This may significantly add to the contribution of ABMT to the outcome of therapy in MM.

Long-Term Follow-Up of Allogeneic Stem Cell Transplantation for Chronic Lymphocytic Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3032-3032
Author(s):  
John Kuruvilla ◽  
Qikun Bao ◽  
Mira Goldberg ◽  
Vikas Gupta ◽  
Thomas L. Kiss ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Conditioning Regimen ◽  
Small Sample ◽  
Unrelated Donor

Abstract Introduction Allogeneic stem cell transplantation (Allo-SCT) remains an option for patients with chronic lymphocytic lymphoma (CLL). Our program employs a strategy using allo-SCT for patients (pts) with high risk disease based on clinical characteristics and prior therapy. We performed a retrospective analysis to examine long-term disease control and treatment toxicity. Methods A total of 52 patients (pts) are included who underwent allo-SCT at our institution between Aug 1989 and Dec 2005. Patients were in a chemosensitive remission at the time of SCT. The conditioning regimen consisted of busulfan (1 mg/kg PO q6h X4 days between 1989–200 and 3.2 mg/kg IV daily X 4days subsequently) and cyclophosphamide 60 mg/kg X 2 days. Cyclophosphamide 60 mg/kg X 2 days and TBI 12 Gy was used for unrelated donor SCT. Reduced intensity conditioning (RIC) SCT were typically performed with Fludarabine 50 mg/m2 for 4 days and 2 Gy TBI. GVHD prophylaxis was with cyclosporine A and methotrexate. Results There were 34 males and 18 females. The median age at the time of transplant was 51 years (range 26 to 65). Histologic subtype was: CLL and/or small lymphocytic lymphoma (SLL); 48 and T-prolymphocytic leukemia (PLL): 4. The median number of prior chemotherapy regimens was 3 (range 1 – 10) and was unavailable in 16. Prior chemotherapies included: anthracycline-based: 24, prior purine analog: 32, prior platinum-based: 8, prior auto-SCT: 1, prior rituximab: 5. The median time from diagnosis to allo-SCT was 58 months (range 5 – 260). 10 pts underwent RIC SCT. Graft source was: matched sibling (MSD) bone marrow (BM): 18, MSD peripheral blood stem cells (PBSC): 20, Mismatch related (MMRD) bone marrow (BM): 1, MRD PBSC: 4, matched unrelated donor (MUD) BM: 8, MUD PBSC: 1. At 5 years, the overall survival of the entire cohort is 51% (95% confidence intervals: 34 – 68%) with two long-term survivors of 14 and 17 years. Treatment-related mortality (TRM) was 20 of 52 pts (38%). 4 pts have relapsed ((8% of total cohort) and non-relapse mortality was 1 pt (2%). Overall survival by intensity of SCT conditioning regimen was not significant (p=0.3). TRM was similar in pts who received fully myeloablative SCT (40% vs. 20% in RICSCT group, p=0.29). Conclusions Acceptable survival post-SCT is possible using an allo-SCT strategy in CLL. However, TRM remains high in this group of heavily pre-treated patients with a median age of over 50 that predominantly received fully myeloablative allo-SCT. Due to small sample size, the potential benefit of reduced TRM with RICSCT cannot be demonstrated. Ideally, allo-SCT should be considered earlier in the course of the disease based on risk stratification utilizing traditional risk factors and modern prognostic factors such as FISH studies and novel markers.

scholarly journals Relapse Risk Score after Allogeneic Stem Cell Transplantation for MDS Patients. an EBMT Study from the MDS Subcommittee of Chronic Malignancies Working Party (CMWP)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4701-4701
Author(s):  
Nicolaus Kröger ◽  
Hein Putter ◽  
Liesbeth De Wreede ◽  
Anja van Biezen ◽  
Dimitris Ziagkos ◽  
...  
Keyword(s):  
Risk Factors ◽  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Research Funding ◽  
Disease Status ◽  
Risk Scores ◽  
Risk Of Relapse

Abstract Introduction The number of MDS patients who receive allogeneic stem cell transplantation is steadily increasing. However, the main cause for treatment failure is relapse which exceeds 50%. Post transplant strategies such as novel agents (5-azacytidine, HDAC inhibitor etc.) as well as adoptive immunotherapy (e.g. DLI) are currently under investigation to reduce the risk of relapse. Patients and methods In order to have a valid tool for stratification in phase III studies, the CMWP of EBMT is developing a simplified "Relapse-risk score" for MDS patients. For this purpose 1638 patients with MDS who received an allogeneic stem cell transplantation from HLA-identical sibling or a matched unrelated donor between 1995 and 2012 and reported to EBMT registry were included. The median age of the patients was 54 years (range 18-76) and diagnosis were: RAR/RARS/RCDM-(RS) and RAEB. Variables which were taken into the analysis were: age, classification of MDS, donor source (HLA-identical sibling vs matched unrelated donors), acute and chronic GvHD,stem cell source (PBSC vs bone marrow), T-cell depletion , intensity of the conditioning regimen (reduced intensity vs standard myeloablative), blasts in bone marrow at time of transplant, and cytogenetic: very poor (very poor according to IPSS revised or monosomal karyotype), poor (according to IPSS-revised), and good (according to IPSS-revised) and unclassifiable. To take the different risks of relapse depending on time from transplant into account we developed 4 different prognostic models: 1) relapse between SCT and 6 months after SCT, 2) relapse between 6 and 12 months post-SCT, 3) relapse between 12 and 24 months post-SCT and 4) relapse after 24 months post-SCT. Results Multivariate Fine and Gray regression models were used to assess the impact of risk factors on the cumulative incidence of relapse. Disease status RAEB remains significant in all 4 models (1: HR 1.62 (95% CI 1.14-2.86), 2: HR 2.51 (95% CI 1.49-4.20), 3: HR 2.10 (95% CI 1.19-3.73), and 4: HR 2.97 (95% 1.56-5.60), whereas very poor cytogenetic was significant in model 1: HR 4.33 (95% CI 2.85-6.60), and model 3: HR 3.51 (95% CI 1.69-7.29)), poor cytogenetic only for early relapse: model 1: HR 2.19 (95% CI 1.39-3.27). RIC was significant for model 1: HR 2.04 (95% CI 1.51-2.75 and 2: HR 1.72 (95% CI 1.06-2.77), T-cell depletion for model 2: HR 1.61 (95% CI 1.02-2.56), and 3: HR 2.01 (95% CI 1.19-3.39). The prognostic risk scores are directly obtained by adding up the relevant log-hazard ratios, which allows dividing patients into three risk groups, low, medium, high, defined by tertiles in the study population. Cumulative incidence plots of relapse for each of the three groups are shown. Conclusion Relapse as most common treatment failure of allogeneic SCT in MDS can occur even after 24 months. Several risk factors influence the incidence of relapse, however while RAEB disease status influence early, intermediate and late relapse, other risk factors such as cGvHD influence only late (>24 months relapse. Therefore, these risk scores may help to stratify patients according to their risk of relapse after stem cell transplantation which can be used for stratification in further prospective trials using post transplant therapies at different time points after stem cell transplantation to reduce the risk of relapse. Figure Figure. Disclosures Kröger: Sanofi: Honoraria, Research Funding. Maertens:Amgen: Consultancy; Merck Sharp & Dohme: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pfizer: Consultancy, Honoraria, Research Funding, Speakers Bureau; Astellas: Consultancy, Speakers Bureau; Gilead: Consultancy, Honoraria, Speakers Bureau. Schetelig:Sanofi: Honoraria.

Cytomegalovirus Infections Following Reduced-Intensity Allogeneic Stem Cell Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2245-2245
Author(s):  
Ryotaro Nakamura ◽  
Sandra Cohen ◽  
Joycelynne Palmer ◽  
Ghislaine Hawkins ◽  
Bernard Tegtmeier ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Univariate Analysis ◽  
Significant Implication ◽  
Cmv Disease ◽  
Cmv Reactivation ◽  
Reduced Intensity

Abstract Reduced intensity allogeneic stem cell transplantation is increasingly used for patients who are at high risk for mortality following conventional full-intensity regimens. Defining the risk of CMV-related events in this growing modality has a significant implication in future immunologic interventions to improve their transplant outcomes. Therefore, we analyzed 160 patients at risk for CMV (R+ and/or D+) who received a reduced intensity transplant (RIT) between May 2000 and February 2004 from either a matched-related (n=91) or unrelaed donor (n=69) under the City of Hope IRB protocol #02047. The median age of the cohort was 51 (range: 15–71) and recipient/donor CMV serostatus was; R+D+=87, R+D-=44, R-D+=29. Conditioning regimens were reduced but myeloablative (fludarabine + melphalan or busulfan) in 124 or truly non-myeloablative (TBI 200cGy +/− fludarabine) in 36 patients. Fourteen received a bone marrow graft and the remaining 146 received PBSC graft. GVHD prophylaxis consisted of cyclosporine and mycophenolate +/− short course of methotrexate. CMV reactivation was monitored by shell vial blood culture (BC) twice a week from d21 until d100 or longer if clinically indicated. Additional monitoring with quantitative PCR was available in 57 patients. Preemptive therapy with ganciclovir was started at the first positive BC at 5mg/kg twice a day for a week, followed by maintenance therapy for 5 weeks. Of 160 patients, at the time of analysis 94 patients are alive with a median follow up of 12.2 months. The actuarial probabilities of overall survival, disease-free survival, and relapse for the entire cohort at 1 year were 55.9 %, (95%CI: 51.1–60.5), 40.4% (95% CI: 37.1–43.7), and 40.1% (95%CI: 34.8–46.2), respectively. Grade 2–4 acute GVHD occurred in 91 (56%) patients. Eighty-one patients developed CMV reactivation (actuarial probability of 52+/−4%) at the median of 44 days post-transplant (range: d20-d216, 8 after d100). Of these, 42 (52%) had either persistent or recurrent reactivation. Nineteen patients (12%) developed CMV disease (8 with pneumonitis, 11 with GI tract) at the median onset of 56 days (range d28-d591: 5 after d100). Seven of these 19 patients had both BC and PCR data, which were consistent each other in all but one. CMV viremia itself did not predict poorer survival (p=NS), but CMV disease was associated with lower overall survival (37% vs. 65%, p=0.02). The univariate analysis revealed two major findings: 1) CMV seropositive patients were at seven times the ‘hazard’ (HR: 7.2, 95%CI: 2.3–22.9) for CMV reactivation compared to those who were CMV seronegative (p<0.001); and 2) patients who received a true non-myeloablative regimen were at decreased ‘risk’ for CMV reactivation compared to those who received fludarabine + melphalan or busulfan (HR: 0.42, 95%CI: 0.2–0.8) (p<0.01). In multivariate analysis these factors remained significant. In summary, our data demonstrate the significant incidence of CMV reactivation and disease in RIT, but true non-myeloablative transplants may have lower risk. Future immunologic or pharmacologic interventions should include RIT patients.

Analysis of Risk Factors and Outcome for Extramedullary Relapses Post Allogeneic Stem Cell Transplantation for Myeloma.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4562-4562
Author(s):  
Myo Htut ◽  
Firoozeh Sahebi ◽  
George Somlo ◽  
Pablo Parker ◽  
Chatchada Karanes ◽  
...  
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Risk Ratio ◽  
Allogeneic Stem Cell Transplantation ◽  
Novel Agents ◽  
Cell Transplant ◽  
Allogeneic Hsct

Abstract Abstract 4562 Analysis of Risk Factors and Outcome for Extramedullary Relapses post Allogeneic Stem Cell Transplantation for Myeloma Relapse after both autologous and allogeneic hematopietic stem cell transplant (HSCT) is common in multiple myeloma (MM). Unusual sites of relapse have been reported after allogeneic HSCT in the form of isolated extramedullary (EM) lesion or light chain escape. It is hypothesized that these EM relapses are due to changes in the marrow microenvironment or selection of resistant subclones from therapy with novel agents and or allogeneic stem cell transplantation. Several case reports have shown that EM relapse is associated with dismal prognosis compared to medullary or bone marrow (BM) relapse. To study the relapse patterns and outcome, we performed a retrospective analysis of 56 pts who underwent tandem autologous-nonmyeloablative allogeneic HSCT (auto-allo) or reduced intensity conditioning (RIC) allogeneic transplant. Between January, 2000 to March 2008, 38 pts received planned auto-allo HSCT using melphalan (200 mg/m2) prior to auto-HSCT and TBI (200 cGy) prior to allo-HSCT and 18 pts received RIC allo-HSCT following fludarabine (125mg/m2) and melphalan 140mg/m2. Donors included 52 HLA matched siblings and 4 matched unrelated donors.Table 1.Patients characteristicsParametersPts without relapse (n)BM relapse (n)EM relapse (n)P-valueTotal number of patients33167.Age at transplant (median, yr.)50.85154.10.84Interval between diagnosis-transplant (median, mo.)11.79.414.60.12B2-micr (median)2.06 (1.18-10)1.67 (1.28-2.15)2.08 (0.79- 9.05)0.15Median f/u for alive pts (yr.)6.88.79.6.Type of transplant....Auto- allo graft70% (23)69 % (11)57 % (4)0.84RIC30% (10)31% (5)43% (3)Response before allograft....CR/PR64% (21)56% (9)71% (5)0.79MR/SD/RE/refractory36% (12)44% (7)29% (2)Stage III disease at the time of transplant78% (25)81% (13)100% (7)0.94Ch 13 del at dx18% (6)12% (2)29% (2)0.69Novel agent prior to transplant45% (15)38% (6)57% (4)0.74 RESULTS After a median follow up of 7.8 years; there were 16 BM and 7 EM relapses. There was no correlation between either relapse or the pattern of relapse (BM and EM) and development of acute and chronic graft vs. chronic disease (GVHD). The risk ratio for BM relapse in 5 year is 0.27 for patients with chronic GVHD (cGVHD) and 0.15 for patients without cGVHD (P=0.69). The risk ratio for EM relapse in 5 year is 0.12 for patients with cGVHD and 0.25 for patients without cGVHD (P=0.10) (Figure 1). Overall survival (OS) and progression-free survival (PFS) for the whole group (N=56) is shown in figure 1. Four year OS was 43% in EM group and 88% in BM group (P=0.005) (Figure 3). There were no significant differences between age, B2 microglobulin, numbers of treatment before HSCT, use of novel agents before HSCT, cytogenetics, stage, transplant regimen and development of GVHD and pattern of relapse (BM vs. EM). In conclusion our data suggest that EM relapse can occur post allogeneic HSCT and is associated with shorter overall survival. The development of GVHD does not prevent against EM relapse. Disclosures: No relevant conflicts of interest to declare.

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