Cardiac and Pulmonary Function Late Effects after Bone Marrow Transplantation in Childhood: Prospective Study on Behalf of EBMT LEWP Group.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1113-1113
Author(s):  
Cornelio Uderzo ◽  
Paola Corti ◽  
Sara Fedeli ◽  
Francesco Tana ◽  
Chiara Messina ◽  
...  
Keyword(s):  
Risk Factors ◽  
Bone Marrow ◽  
Multivariate Analysis ◽  
Bone Marrow Transplantation ◽  
Pulmonary Function ◽  
Late Effects ◽  
Cumulative Incidence ◽  
Hazard Rate ◽  
Conditioning Regimen

Abstract BACKGROUND Patients (pts) undergoing bone marrow transplantation (BMT) for hematological childhood disorders might present long-term cardiac and pulmonary function (CPF) complications. The current study assessed incidence and risk factors of CPF late sequelae by a multicenter study. METHODS From March 1994 to December 1997 we enrolled 220 consecutive children (130 males, median age at BMT 9,5 yrs) who underwent BMT (162 allogeneic and 58 autologous) for malignant (193) and non malignant (27) diseases in 9 EBMT centers. Total body irradiation (TBI) based conditioning regimen was used in 120/220 pts. A total of 165/220 pts were alive at the end of the study with a reliable CPF assessment which consisted of pulmonary function tests (PFTs) and M-Mode echocardiography performed at pre-BMT phase, at 1st year post-BMT and yearly. Statistical analysis to evaluate the difference between pre-BMT and post-BMT CPF was performed by paired t-test, while the assessment of risk factors was based on univariate and multivariate analysis. RESULTS Median follow-up of evaluable pts was 5 yrs (range 4–8 yrs). Fifty-five of 220 patients deceased, none for late CPF abnormalities. The 5-year cumulative incidence of lung and cardiac impairment was 35% (hazard rate=0,07) and 23% (hazard rate =0,04) respectively. Patients presenting abnormal PFTs and shortening fraction (SF) at last follow-up were 15% and 12% respectively, even if asymptomatic. Chronic GVHD was a major risk factor in reducing lung function at both univariate (P=0.02) and multivariate analysis (P=0,006). Patients undergoing TBI based conditioning regimen showed a SF impairment at multivariate analysis (P=0,03). Gender, age, diagnosis, pre-BMT anthracyclines, BMT type, non-TBI based conditioning, malignant or non malignant diseases at BMT were not significantly related to pulmonary and cardiac late effects. No difference was ascertained in the cumulative incidence of non relapse mortality in a competing risk setting which suggests that BMT can also be successful for those children who experienced both abnormal PFTs and SF. At the end of the study all surviving pts had a median Lansky index >90. CONCLUSIONS Our study focused on low incidence of only asymptomatic CPF late effects in children transplanted for hematological disorders. TBI for cardiac function and C-GVHD for pulmonary function are the most important risk factors. Despite most of the alive pts remains in the normal range both for CPF complications from the beginning of BMT up to 5th year of median follow-up, a continue surveillance at least in adolescent age is recommended.

Outcome Of Bone Marrow Transplantation In Lebanese Children With β-Thalassemia Major

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5505-5505
Author(s):  
Adlette Inati ◽  
Javid Gaziev ◽  
Hussein A Abbas ◽  
Serge Korjian ◽  
Yazan Daaboul ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Iron Overload ◽  
Late Effects ◽  
Marrow Transplantation ◽  
Acute Gvhd ◽  
Conditioning Regimen ◽  
Thalassemia Major ◽  
Increased Risk

Abstract Abstract 5505 Introduction Bone marrow transplantation (BMT) represents the only curative modality for β-Thalassemia Major (β–TM). Best results are achieved in regularly transfused and chelated pediatric patients. Outcome of BMT in 36 Lebanese children who received treatment in the Mediterranean Institute of Hematology (IME) centers in Italy is presented. Methods 36 children with β–TM treated at Chronic Care Center, Lebanon underwent BMT from HLA compatible donors in IME centers.  Each was assigned a Pesaro risk category and underwent a percutaneous liver biopsy before BMT. Conditioning regimen consisted of busulfan, cyclophosphamide ± Thiotepa and ATG. GvHD prophylaxis included cyclosporine A, methotrexate and prednisolone. Engraftment was evaluated by fluorescence in situ hybridization. Transplant related mortality (TRM) and other complications were calculated as cumulative incidence. Analyses were performed using R software. Results 36 hepatitis B and C negative children with β –TM (M/F 1:l),  median age 8.5 years, underwent BMT from HLA identical donors. The most common β-globin mutation was homozygous IVS1.110 (39.29%). 20.5%, 55.9% and 23.5% had Pesaro risk class 1, 2 and 3, respectively.  Mean injected CD34+ cells, total nucleated cells and CD3+ cells/recipient  were 10.9x106 /Kg,  8.69x108/Kg and 66.3x106 /Kg. Absolute neutrophil count >0.5 x109 and platelet count >20 x 109 were reached in all patients within a mean of +19.44±4 and +19.15 ±6.5 days. Regular chimerism surveillance  showed complete engraftment in 35/36 children (97.3%)  up till+ 4.2 years median follow up. 1/36 (2.7%) had partial engraftment but continued to be transfusion independent with a mean Hb of 9g/dcl for +1155 days. Immune reconstitution was seen in all patients by + 12 -18 months. At a median follow up of + 6.20 years, 32/36 (89%) of children are alive and transfusion independent. Among those who died (11%), 1 had multi organ failure, 2 had grade 4 acute GvHD and 1 had fulminant interstitial pneumonitis.  47% had acute GvHD which was not correlated with donor relation, conditioning regimen, and pre-BMT hepatomegaly, splenomegaly and transfusion frequency. 8/36 (22%) had grade 2 to 4 acute GvHD of which 75% resolved on treatment while 25% (all grade 4) were fatal. 9/32 (28%) surviving children had chronic GvHD completely resolved on treatment and not correlated with  any recipient, donor or treatment feature.  Other transplant related complications included CMV reactivation, sepsis, EBV and candida infections, hemorrhagic cystitis, cerebral toxoplasmosis, tuberculosis and transient cyclosporine  related renal and neurotoxicity, all completely resolved on treatment. Late effects of transplant were monitored in 27 children.  Iron overload data utilizing magnetic resonance imaging at + 3.1 year median follow up showed that mean baseline LIC for 27 patients was 11.3 mg Fe/g dw but ranged as high as 36.6 mg Fe/g dw. Median serum ferritin was 1255 ng/mL, with a maximum of 5884 ng/mL.  9/27 (33.3%) children had significant iron overload defined as SF >2500 ng/ml, or LIC >15 mg Fe/g dw, or T2* <20 msec, levels known to be associated with increased risk of progressive organ dysfunction and death. Median ejection fraction was 68 % (range 58-75%). Up till + 6.20 years median follow up,  serum immunoglobulins, alanine and aspartate aminotransferases, BUN, creatinine and creatinine clearance were normal in all 27 children.  Hypothyroidism, growth retardation and diffuse persistent vitiligo were seen in 3/25 (12%), 4/25 (16%) and 1/25 (4%) survivors respectively. Summary Our results reflect an excellent outcome for Lebanese children with β –TM undergoing transplantation. TRM was low and associated complications were transient and manageable. Significant iron overload was, however, noted years after BMT underscoring the need for long term monitoring for iron overload and for iron removal to prevent associated negative outcomes.  This study highlights the need for monitoring for late effects for years after transplant. It also demonstrates the effectiveness of international collaboration in facilitating cure for thalassemia in developing countries as Lebanon. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Improved Outcomes in Patients with Thalassemia Major Transplanted with Peripheral Blood and Marrow Grafts in Comparison with Cord Blood and Bone Marrow Grafts from Sibling Donors

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 847-847
Author(s):  
Qiao chuan Li ◽  
Jian ming Luo ◽  
Zhong ming Zhang ◽  
Lian jin Liu ◽  
Ling ling Shi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Cord Blood ◽  
Graft Rejection ◽  
Peripheral Blood ◽  
Cumulative Incidence ◽  
Conditioning Regimen ◽  
Thalassemia Major ◽  
Matched Sibling

Abstract Background: Thalassemia major (TM) is a fatal genetic disease currently only curable with allogeneic stem cell transplantation. This is limited by the lack of suitable donors and the quantity of collected stem cells, and is often complicated by graft rejection and graft versus host disease (GVHD). Methods: The aim of the study was to compare the outcomes of TM patients transplanted with matched sibling cord blood (CB) and bone marrow (BM) grafts vs. matched sibling peripheral blood (PB) stem cell and BM grafts. The trial was designed as a prospective, open-label, single-center clinical protocol, where 204 TM patients were enrolled between January 2007 and November 2015 and transplanted with either PB + BM (n=99) or CB+BM (n=105), from an HLA-identical sibling donor. This study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Guangxi Medical University and was registered at the Chinese Bone Marrow Transplant Registry (CBMTR). The primary end point was 2-year thalassemia free survival(TFS). Secondary end points included 2-year overall survival (OS), the cumulative incidence of GVHD, transplant related mortality (TRM), graft rejection (GF).The conditioning regimen were:1) busulphan (BU) (1.25 mg/kg) given orally four times per day for 4 days or 1mg/kg given intravenously (IV) four times per day for 4 days (day -9 to day -6); 2) fludarabine (FLU) (50mg/m2/day) given IV for 3 days (day -12 to day -11); 3) cyclophosphamide (CTX) (50 mg/kg/day) given IV for 4 days (day -5 to day -4); 4) anti-thymocytes globulin (ATG, Genzyme ) (2.5 mg/kg/day) given IV for 4 days (days -4 and day -1). All patients were placed on 30 mg/kg hydroxyurea orally once daily for 2-3 months before transplantation.GVHD prophylaxis consisted of a combination of cyclosporin A, methotrexate and mycophenolate mofetil regimen. [BMT 2009; 43(1):61-67]. Results : Patient and donor characteristics, and transplantation outcomes are listed in Tables 1 and 2, respectively. Data cut off for survival follow-up was March 31, 2016. The median follow-up time was 26 months (range, 4 months -105 months). Both neutrophil as well as platelet engraftment occurred significantly faster in the PB+ BM group than the CB+BM group (11 days vs. 13 days, P=0.001 and 15 days vs. 25 days, P=0.001, respectively). The rate of GF was the same in both groups (1.0%). The cumulative incidence of grade II-IV acute (a) GVHD and extensive chronic (c)GVHD in the PB+ BM group was higher than the CB+BM group: aGVHD=15.5% vs 1.0%, P=0.001; cGVHD= 6.4% vs. 0%, P=0.013. The cumulative rates of TRM at 2 years remained significantly lower in the PB+BM group compared to the CB+BM group with 2.0% and 12.5%,(P=0.005), respectively . Both OS and TFS at 2 years favored the PB +BM group compared to the CB+BM group : OS=98% vs. 86.5%,P=0.003;TFS= 97% vs. 86.5%, P=0.008.(Fig 1) Conclusion: Our results demonstrate that grafts composed of PB + BM had superior overall outcomes compared to CB + BM grafts, as evidenced by faster engraftment and lower TRM of the former despite substantially lower aGVHD and cGVHD rates of the latter. The mixed stem cell populaitons and the high cell dose achieved with the use of 2 different graft sources, toghether with the conditioning regimen used likely contributed to the superior outcomes seen with this regiem. This strategy could be of great benefit for the treatment of patient with TM and other benign hematologic disease. Disclosures No relevant conflicts of interest to declare.

scholarly journals Multivariate analysis of risk factors in stage 4 neuroblastoma patients over the age of one year treated with megatherapy and stem-cell transplantation: a report from the European Bone Marrow Transplantation Solid Tumor Registry.

1998 ◽  
Vol 16 (3) ◽  
pp. 953-965 ◽  
Author(s):  
R Ladenstein ◽  
T Philip ◽  
C Lasset ◽  
O Hartmann ◽  
A Garaventa ◽  
...  
Keyword(s):  
Risk Factors ◽  
Bone Marrow ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Bone Marrow Transplantation ◽  
Stem Cell Transplantation ◽  
Solid Tumor ◽  
Partial Remission ◽  
Bone Marrow Involvement ◽  
Tumor Registry

PURPOSE The European Bone Marrow Transplantation (EBMT) Solid Tumor Registry (STR) contains detailed information on children with advanced neuroblastoma who, after standard-dose induction chemotherapy and surgery, received myeloablative megatherapy (MGT) followed by stem-cell transplantation (SCT). This data base was analyzed to identify factors that predict event-free survival (EFS). PATIENTS AND METHODS Eligibility criteria were stage IV neuroblastoma, age over 1 year at diagnosis, and no relapse before MGT/SCT. Between February 1978 and July 1992, 549 patients were registered by 36 European transplant centers. The median age at diagnosis was 36 months (range, 13 to 216 months) and the male-female ratio was 1:45. Before MGT, 157 patients were in complete remission (CR), 156 in very good partial remission (VGPR), and 208 in partial remission (PR), whereas 24 had had only a minor response (MR). One hundred ten of 546 patients had undergone two successive MGT procedures. The median observation time was 60 months (range, 12 to 187 months). RESULTS Actuarial EFS is 26% at 5 years. Multivariate analysis by the Cox proportional hazards regression model included 529 patients with complete data sets. After adjustment for treatment duration before MGT and double MGT procedures, two adverse, independent risk factors that influenced EFS were identified: (1) persisting skeletal lesions before MGT as defined by technetium (99TC) scans and/or meta-iodobenzylguanidine (mIBG) scans (P = .004) and (2) persisting bone marrow involvement before MGT (P = .03). CONCLUSION After induction treatment, persisting skeletal disease as defined above and persisting bone marrow involvement may be predictive of a particularly poor outcome. Physicians may consider this an additional important tool to decide the patient's management.

Allogeneic bone marrow transplantation for children with acute myeloblastic leukemia in first complete remission: impact of conditioning regimen without total-body irradiation--a report from the Société Française de Greffe de Moelle.

1994 ◽  
Vol 12 (6) ◽  
pp. 1217-1222 ◽  
Author(s):  
G Michel ◽  
E Gluckman ◽  
H Esperou-Bourdeau ◽  
J Reiffers ◽  
J L Pico ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Multivariate Analysis ◽  
Bone Marrow Transplantation ◽  
High Risk ◽  
Complete Remission ◽  
Total Body Irradiation ◽  
Conditioning Regimen ◽  
Total Body ◽  
First Complete Remission ◽  
Risk Of Relapse

PURPOSE To analyze the French experience of chemotherapeutic preparation before human leukocyte antigen (HLA)-identical bone marrow transplantation (BMT) in children with acute myeloblastic leukemia (AML) in first complete remission (CR). PATIENTS AND METHODS The data base used for this study was a French BMT registry for childhood AML. Twenty-three children were conditioned with busulfan and 120 mg/kg cyclophosphamide (Bu-Cy 120 group). Nineteen received busulfan and 200 mg/kg cyclophosphamide (Bu-Cy200 group). During the same time period, 32 patients were prepared with total-body irradiation (TBI group) most often in combination with 120 mg/kg of cyclophosphamide. RESULTS The probability of relapse was 54%, 13%, and 10% for the Bu-Cy120, Bu-Cy200, and TBI groups, respectively (P < .05 in the univariate analysis, log-rank test, 2 df). In the multivariate analysis, a conditioning regimen with Bu-Cy120 was significantly associated with a higher risk of relapse (P = .02; relative risk, 3.62). The probability of transplant-related mortality (TRM) was 0% for Bu-Cy120, 5% for Bu-Cy200, and 10% for TBI. Kaplan-Meier estimations of event-free survival (EFS) were 46% +/- 24%, 82% +/- 18%, and 80% +/- 14%, respectively, for the three groups, with median follow-up durations of 28 months (range, 3 to 78), 31 months (4 to 68), and 48 months (2 to 73). In the multivariate analysis, two factors adversely affected EFS: a conditioning regimen with Bu-Cy120 (P = .07) and a long interval from diagnosis to BMT (> or = 120 days, P = .08). CONCLUSION Bu-Cy120 is a well-tolerated preparation, but results in a high risk of relapse for children with AML in first CR. This high risk of relapse is not observed when the dose of cyclophosphamide is increased to 200 mg/kg.

scholarly journals Increased incidence of solid malignant tumors after bone marrow transplantation for severe aplastic anemia [see comments]

Blood ◽  
1991 ◽  
Vol 78 (2) ◽  
pp. 277-279 ◽  
Author(s):  
G Socie ◽  
M Henry-Amar ◽  
JM Cosset ◽  
A Devergie ◽  
T Girinsky ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Aplastic Anemia ◽  
Marrow Transplantation ◽  
Malignant Tumors ◽  
Conditioning Regimen ◽  
Severe Aplastic Anemia ◽  
Male Patients

Abstract From May 1980 to December 1989, 107 consecutive patients with non- constitutional severe aplastic anemia underwent bone marrow transplantation at our institution using cyclophosphamide and thoraco- abdominal irradiation as conditioning regimen. During the same period, 40 patients with Fanconi anemia were also grafted after a similar conditioning, giving a total series of 147 patients. With a mean follow- up of 64 months, four male patients developed a solid malignant tumor, a number that leads to an 8-year cumulative incidence rate of 22% (eg, relative risk to general population = 41, P less than .001). These results should be considered as a warning to clinicians who follow these successfully grafted long-term patients.

Serum Neutrophil Extracellular Traps (NETs) Are a Potential Predictive Marker for Thrombotic Microangiopathy (TMA) After Allogeneic Stem Cell Transplantation

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1919-1919
Author(s):  
Yasuyuki Arai ◽  
Soichiro Sakamoto ◽  
Kouhei Yamashita ◽  
Kiyomi Mizugishi ◽  
Toshiyuki Kitano ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Thrombotic Microangiopathy ◽  
Cumulative Incidence ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Neutrophil Extracellular Traps ◽  
Blood Type ◽  
Extracellular Traps ◽  
Activated Neutrophils

Abstract Abstract 1919 Background: Neutrophil extracellular traps (NETs), originally discovered as a component of innate antimicrobial immunity, are chromatin and granule proteins released from activated neutrophils to form extracellular fibrillar matrices. Recently, NETs have been proven to contribute to inflammation and thrombosis and are elevated during such diseases as systemic lupus erythematosus, sepsis, and thrombotic thrombocytopenic purpura. Following allo-SCT, patients are often prone to infectious and thrombotic episodes, especially those complicated with SCT-associated thrombotic microangiopathy (TMA). However, the relevance of serum NETs to the incidence of TMA after allo-SCT has not been reported. This study aimed to analyze serum NET trends during allo-SCT and define their effects on the risks of TMA. Patients and Methods: We retrospectively reviewed the clinical history of patients who underwent allo-SCT in our department between Sept 2007 and Apr 2012. Patients' serum specimens were collected at 3 different times (before conditioning regimen [PRE], on Day0, and Day 28 [4WK]). TMA was diagnosed according to the EBMT criteria (schistocytes increase, thrombocytopenia, LDH elevation, and decrease of hemoglobin and haptoglobin levels). Patients who met these criteria at least once were included in the TMA group. The serum specimens were analyzed using PicoGreen dsDNA Quantitation Kits (Invitrogen). Univariate analyses for the cumulative incidence of TMA were carried out using Gray's methods considering death as a competing risk. Factors associated with at least borderline significance (p < 0.10) were subjected to a multivariate analysis, using Fine-Gray proportional hazards models. Results: Ninety patients were included (M:F, 50:40), whose age ranged from 17 to 66 years (median, 48.5). The underlying diseases were AML in 34; MDS, 10; ALL, 16; ML, 21; and others, 9 patients. Disease status at SCT was progressive (less than PR) in 36 cases. Donors were related in 20 cases. Myeloablative conditioning (MAC) was performed in 39 cases. Prophylaxis for aGVHD comprised a calcineurin inhibitor (CNI, CyA; 16, FK506; 74) plus MTX (47 cases) or MMF (7 cases). With the median follow-up of 700 days (range, 98–1660), TMA was reported in 11 cases, at a median of 42 days (range, 19–78) after SCT, and the cumulative incidence was 12.2% (95% CI, 6.5–19.9%). The serum NET values of PRE (102.7 ± 4.9 ng/mL, mean ± standard error mean) or Day0 (102.6 ± 4.4) for SCT patients were almost similar to those for healthy donors (107.0 ± 5.2, n = 10). In contrast, the values at 4WK for SCT patients were apparently elevated (123.6 ± 5.9), especially in the TMA group (150.3 ± 13.3). Interestingly, the ratio of Day0 to PRE values (Day0/PRE) and 4WK to PRE (4WK/PRE) were significantly higher in the TMA group, compared with non-TMA group (1.18 ± 0.05 vs 1.03 ± 0.02 in Day0/PRE [p = 0.03], and 1.76 ± 0.13 vs 1.23 ± 0.06 in 4WK/PRE [p < 0.01]). Univariate analysis showed that the incidence of TMA was significantly higher in patients with Day0/PRE > 1.1 (36 cases) than those with a ratio ≤ 1.1 (54 cases) (22.2 vs 5.6%, p = 0.01). Other risk factors of TMA were blood-type minor mismatch (incidence of TMA; 17.2 vs 3.1%), and progressive disease (22.2 vs 5.6%). Non-significant factors included donor source, sex, older age, underlying disease, MAC, TBI, and type of CNI (p > 0.10). Multivariate analysis showed that Day0/PRE > 1.1 was significant (hazard ratio 4.55, p = 0.04). The 1-year OS was significantly lower (31.2 vs 69.8% [p < 0.01]) and TRM was higher (39.0 vs 9.3% [p = 0.03]) in the TMA group than in the non-TMA group. Day0/PRE ratio did not have a significant impact on the incidence of other early complications such as aGVHD (38.9 vs 55.6%) or bacterial infections (55.6 vs 37.0%) in the Day0/PRE > 1.1 and ≤ 1.1 groups. Conclusion: Higher 4WK/PRE ratios of serum NETs showed the possible contribution of NETs to the pathogenesis of TMA. Elevation of Day0/PRE ratios was shown to significantly increase the incidence of TMA after SCT. Increased amounts of intravascular NETs released from activated neutrophils following conditioning regimens may cause endothelial damage and thrombotic tendencies associated with platelet aggregation, resulting in TMA coupled with other post-transplant factors such as infection, CNI administration, and GVHD. A Day0/PRE serum NET ratio > 1.1 is a risk factor for TMA, and prophylactic strategies should be attempted to improve the outcomes of allo-SCT. Disclosures: No relevant conflicts of interest to declare.

Second Malignancies After Autologous Hematopoietic Cell Transplantation (AHCT) for Multiple Myeloma (MM): A Center for International Blood and Marrow Transplant Research (CIBMTR) Analysis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 591-591
Author(s):  
Girindra Raval ◽  
Anuj Mahindra ◽  
Xiaobo Zhong ◽  
Ruta Brazauskas ◽  
Robert Peter Gale ◽  
...  
Keyword(s):  
Risk Factors ◽  
At Risk ◽  
Multivariate Analysis ◽  
General Population ◽  
Cumulative Incidence ◽  
Incidence Rates ◽  
High Dose ◽  
Risk Of Death ◽  
Age And Sex

Abstract Abstract 591 Background: Survival of patients with MM has improved over the past two decades, in part due to the use of AHCT. Increasingly, second primary malignancies (SPMs) are observed in MM survivors. Determining the baseline incidence and risk factors associated with SPMs after AHCT is important to assess risk and to evaluate the risk-benefit ratio of newer therapies. Methods: We analyzed the incidence of SPMs in 3784 MM patients receiving (“upfront”) AHCT for MM within 18 months of diagnosis between 1990 and 2010 and reported to the CIBMTR. Cumulative incidence rates of SPMs were estimated taking into account the competing risk of death. For each transplant recipient, the number of person-years at risk was calculated from the date of transplantation until date of last contact, death, or diagnosis of SPM, whichever occurred first. Incidence rates for all invasive cancers in the general population were obtained from the SEER database. Age-, sex-, and race- specific incidence rates for overall SPMs and particular anatomical sites were applied to the appropriate person-years at risk to compute the expected numbers of cancers. Observed–to –expected (O/E) ratios were calculated, and Poisson distribution 99% confidence intervals (CIs) were generated. Poisson regression model was used to analyze risk factors for overall SPMs and AML/MDS. Results: Pre-transplant therapy included novel agents in 56% including thalidomide (35%), lenalidomide (9%), bortezomib (16%) or their combinations (11%). Majority (80%) received high dose melphalan conditioning. Post-transplant maintenance therapy included thalidomide (16%), lenalidomide (8%), bortezomib (9%) and interferon (6%). Median follow-up of survivors was 52 months (range 3 to 192 months).With 12707 person years of follow up, 153 new malignancies were reported with a crude rate of 1.2 SPM per 100 person years of follow up. Observed/Expected [O/E] ratio for all SPMs was 0.99 (99% CI, 0.80–1.22). Cumulative incidence of SPM overall was 2.48% (95% CI, 1.96–3.05) at 3 years and 6.0% (95% CI, 4.96–7.10) at 7 years [Figure 1]. Individual SPMs observed significantly more frequently than expected are summarized in Table 1. The cumulative incidence of MDS/AML was 0.5% (95% CI, 0.28–0.78) at 3 years and 1.3 (95% CI, 0.85– 1.9%) at 7 years. Majority had MM progression prior to diagnosis of SPM (65 of 102 patients overall and 15 of 23 patients for MDS/AML). In multivariate analysis, significant risk factors for development of SPMs included: obesity [Hazard ratio = HR 1.89(95%CI, 1.21–2.93), p=0.0047 for BMI>30 vs. BMI<25], older age: [HR10.53 (95%CI, 1.46–75.82), p=0.0195] for 60–69 year olds and HR14.4 (95%CI, 1.89–109.75), p=0.01 for 70+ year olds compared to the 18–39 year old group. Specific conditioning regimens did not correlate with the risk of SPM. The low number of MDS/AML (33 events out of 3784 cases) limited the power of multivariate analysis. Increasing age was significantly associated with development of MDS (HR10.77, (95%CI,92.09–55.51), p=0.004 for 70+ year old vs. 40–49 year olds). Conclusion: In this large cohort of AHCT recipients for MM, the incidence of MDS/AML, melanoma and other skin cancers was significantly higher compared to age and sex matched general population. However the overall risk of SPM was similar to that expected for age and sex matched population. It was also similar to the placebo arms of recent reports by McCarthy Pl et al and Attal M et al (N Engl J Med. 10; 366(19):1770–91). Lenalidomide (8%) or thalidomide maintenance (16%) used in a small subset of patients with comparatively short follow up, was not associated with risk of SPM in the analysis of the overall cohort. Disclosures: Gale: Celgene: Employment. Brandenburg:Celgene: Employment, Equity Ownership. Lonial:Millennium, Celgene, Novartis, BMS, Onyx, Merck all Consultancy. Krishnan:Celgene and Millennium: Consultancy, Speakers Bureau. Dispenzieri:Celgene and Millennium: Research Funding. Hari:Celgene: Consultancy, Honoraria.

scholarly journals 52Fe for additional marrow ablation before bone marrow transplantation

Blood ◽  
1993 ◽  
Vol 81 (12) ◽  
pp. 3435-3439 ◽  
Author(s):  
A Ferrant ◽  
M Cogneau ◽  
N Leners ◽  
F Jamar ◽  
P Martiat ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Conditioning Regimen ◽  
Absorbed Dose ◽  
Hematologic Malignancies ◽  
Whole Body ◽  
Median Percentage ◽  
Preparative Regimen

Abstract The effectiveness of bone marrow transplantation (BMT) for malignant blood diseases remains limited by the inability of the preparative regimen to eliminate the disease without causing toxicity to normal organs. We have used 52Fe to deliver radiotherapy selectively to the BM. Fourteen patients with hematologic malignancies received 52Fe before a conventional BMT conditioning regimen. The median 52Fe dose was 58 mCi (range, 32 to 85 mCi). As evaluated by quantitative scanning, the median percentage of 52Fe taken up by the BM was 82% (range, 36% to 90%). This resulted in a median radiation-absorbed dose to the BM of 632 rad (range, 151 to 1,144 rad). The median uptake of 52Fe by the liver was 18% (range, 10% to 64%) and the median radiation-absorbed dose to the liver was 239 rad (range, 82 to 526 rad). The median whole body radiation-absorbed dose was 46 rad (range, 22 to 68 rad). No untoward effects were noted after the injections of 52Fe. The patients recovered hematopoiesis without toxicity in excess of that expected with conventional conditioning alone. The median follow-up was 8 months and three patients have relapsed. 52Fe should provide a way to boost the radiation dose to marrow-based diseases before marrow transplantation without increasing toxicity.

scholarly journals Bone marrow transplantation in 107 patients with severe aplastic anemia using cyclophosphamide and thoraco-abdominal irradiation for conditioning: long-term follow-up

Blood ◽  
1991 ◽  
Vol 78 (9) ◽  
pp. 2451-2455 ◽  
Author(s):  
E Gluckman ◽  
G Socie ◽  
A Devergie ◽  
H Bourdeau-Esperou ◽  
R Traineau ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Multivariate Analysis ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Long Term Follow Up ◽  
Abdominal Irradiation

Since 1980, 107 consecutive patients (pts) underwent bone marrow transplantation (BMT) for nonconstitutional severe aplastic anemia (SAA) at our institution. All received conditioning with Cytoxan (150 mg/kg) and thoraco-abdominal irradiation (6 Gy) from an HLA-identical sibling donor. Mean age was 19 years (5 to 46 years). Forty-nine pts had less than 0.2 x 10(9)/L PMN and 53 failed to respond to previous immunosuppressive therapy before BMT. Graft-versus-host disease (GVHD) prophylaxis consisted of methotrexate (22 pts), cyclosporine (52 pts), or both (33 pts). With a median follow-up of 45 months (12 to 120 months), overall actuarial survival was 68% (confidence interval 95%:9.7). Of 16 factors tested, five were shown to adversely influence survival by multivariate analysis: grade greater than or equal to 2 acute GVHD (relative risk [RR]: 5.5), prior immunosuppressive therapy (RR: 3.5), female as donor (RR: 2.4), nonidiopathic SAA (RR: 2), and more than 0.2 x 10(9)/L PMN AA (RR: 2). Because acute GVHD was the most potent factor for survival, we analysed risk factors for acute GVHD. By multivariate analysis, 2 of 14 factors tested were independent: male as recipient (RR: 3) and previous alloimmunization of the donor (RR: 4.3). On long-term follow-up, chronic GVHD was observed in 49 pts of 89 surviving more than 100 days (55%). Multivariate analysis showed that infection before transplant (RR: 1.3) and previous history of acute GVHD (RR: 1.8) were associated with an increased risk of chronic GVHD.

scholarly journals Bone marrow transplantation in 107 patients with severe aplastic anemia using cyclophosphamide and thoraco-abdominal irradiation for conditioning: long-term follow-up

Blood ◽  
1991 ◽  
Vol 78 (9) ◽  
pp. 2451-2455 ◽  
Author(s):  
E Gluckman ◽  
G Socie ◽  
A Devergie ◽  
H Bourdeau-Esperou ◽  
R Traineau ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Multivariate Analysis ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Long Term Follow Up ◽  
Abdominal Irradiation

Abstract Since 1980, 107 consecutive patients (pts) underwent bone marrow transplantation (BMT) for nonconstitutional severe aplastic anemia (SAA) at our institution. All received conditioning with Cytoxan (150 mg/kg) and thoraco-abdominal irradiation (6 Gy) from an HLA-identical sibling donor. Mean age was 19 years (5 to 46 years). Forty-nine pts had less than 0.2 x 10(9)/L PMN and 53 failed to respond to previous immunosuppressive therapy before BMT. Graft-versus-host disease (GVHD) prophylaxis consisted of methotrexate (22 pts), cyclosporine (52 pts), or both (33 pts). With a median follow-up of 45 months (12 to 120 months), overall actuarial survival was 68% (confidence interval 95%:9.7). Of 16 factors tested, five were shown to adversely influence survival by multivariate analysis: grade greater than or equal to 2 acute GVHD (relative risk [RR]: 5.5), prior immunosuppressive therapy (RR: 3.5), female as donor (RR: 2.4), nonidiopathic SAA (RR: 2), and more than 0.2 x 10(9)/L PMN AA (RR: 2). Because acute GVHD was the most potent factor for survival, we analysed risk factors for acute GVHD. By multivariate analysis, 2 of 14 factors tested were independent: male as recipient (RR: 3) and previous alloimmunization of the donor (RR: 4.3). On long-term follow-up, chronic GVHD was observed in 49 pts of 89 surviving more than 100 days (55%). Multivariate analysis showed that infection before transplant (RR: 1.3) and previous history of acute GVHD (RR: 1.8) were associated with an increased risk of chronic GVHD.

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