Abstract
Abstract 2266
We conducted a national retrospective analysis on 63 patients (pts) with either myeloid or lymphoid BC CML who underwent a first allogeneic stem cell transplantation as ...consolidation therapy for BC, since 2000 in France and look at whether 1st and 2nd generation TKIs ±chemotherapy prior to transplant may impact on outcome. There were 46 males and 17 females, and the median age at transplant was 34 (range 3–63) years and the median delay between BC and transplant was 19.6 (2.3-113) months. Thirty six (57%) pts were in chronic phase (CP), 3 (5%) in accelerated and 24 (38%) in BC at CML diagnosis. Twenty three pts received 1 line of treatment, 26 pts 2 lines, and 14 pts 3 or more lines for CML treatment before BC. For BC treatment, 25/63 (39%) pts had chemotherapy without TKI and 29/63 (46%) had TKIs combined or not to chemotherapy (6 chemo+dasatinib, 4 chemo+imatinib, 8 dasatinib alone, 1 dasatinib and imatinib, 9 imatinib, 9 unknown). At transplant 35/63 (55%) were considered in 2nd CP and 28 (45%) still in BC. The majority of the pts had an identical sibling donor (42/63: 66%), 1 mismatched related, 7 matched unrelated, and 13 mismatched unrelated. Fifty-six (89%) pts had a standard conditioning regimen, 7 (11%) pts a RIC regimen and 39 (62%) had a TBI. The stem cell source was bone marrow in 33/63 (52%) pts, PBSC in 24/63 (38%) and cord blood for 6/63 (10%). Fourteen transplants were sex-mismatched (female donor for male recipient). The EBMT-Gratwohl score was low (1+2+3) for 35/63 (55%) pts, intermediate (4) for 14 pts and high (5) for 9 pts, (and 6) for 3 pts and undetermined for 2 pts. The median follow-up since transplant was 25 (range 0.43–109) months. The overall median time for neutrophil recovery (neutrophils > 0.5 109/l) was 20 days. Fourty-one (65%) pts had an aGVHD (29 grade i-II and 12 grade III-IV) with no statistical differences between stem cell sources (p=0.4 for cord vs BM and 0.58 for PBSC vs BM). The cumulative incidence of chronic GVHD (14 extensive, 10 limited) was 43% at latest follow-up, more frequent in RIC transplant. The cumulative incidence of CML relapse was 38% at 2 yrs and multivariate analysis demonstrated the significant impact on relapse of the status at transplant in favour of disease control prior to transplant HR 2.22 (1-4.93, p=0.05 and unexpectedly, no impact of BC treatment with or without TKIs prior to transplant and of other variables. The median overall survival (OS) was 22 months (see Figure 1).
The TRM was 33% at latest follow-up, and it was significantly negatively influenced by the EBMT score (p=0.0077 for scores ≥ 4), BC status at diagnosis (p=0.04). The OS was not improved when using standard conditioning regimens (p=ns), but was improved by disease status at transplant (2nd CP better than persistent BC, p=0.01) and transplant with cord blood and BM stem cell sources over PBSC (p=0.011). Multivariate analysis on OS detected as significant adverse prognosis factors EBMT score ≥5 (HR=4.63 EBMT 5, and 4.77 EBMT 6). The types of treatment of BC CML had no significant impact (with or without stratification on chemotherapy). The median progression-free survival (PFS) was 5.8 months (see Figure 2).
The PFS was not significantly improved by standard conditioning regimens but again was improved by disease control prior to transplant (2nd CP better than persistent BC, p=0.001) and with cord blood and BM stem cell sources over PBSC (p=0.057). Multivariate analysis on PFS detected as significant adverse prognosis factors EBMT score ≥5 (HR=5.82 EBMT 5, and 3.82 EBMT 6), but again, the types of treatment of BC CML prior to transplant had no significant impact.
In conclusion, this analysis suggests that OS and PFS rates are significantly improved when compared to figures from the pre-TKI era. The use of 1st or 2nd generation TKIs alone or combined to chemotherapy does not seem to influence transplant results. CML status and the EBMT score are the major factors that can significantly influence transplant outcome.
Disclosures:
No relevant conflicts of interest to declare.
Abstract 2266
We conducted a national retrospective analysis on 63 patients (pts) with either myeloid or lymphoid BC CML who underwent a first allogeneic stem cell transplantation as consolidation ...therapy for BC, since 2000 in France and look at whether 1st and 2nd generation TKIs ±chemotherapy prior to transplant may impact on outcome. There were 46 males and 17 females, and the median age at transplant was 34 (range 3–63) years and the median delay between BC and transplant was 19.6 (2.3-113) months. Thirty six (57%) pts were in chronic phase (CP), 3 (5%) in accelerated and 24 (38%) in BC at CML diagnosis. Twenty three pts received 1 line of treatment, 26 pts 2 lines, and 14 pts 3 or more lines for CML treatment before BC. For BC treatment, 25/63 (39%) pts had chemotherapy without TKI and 29/63 (46%) had TKIs combined or not to chemotherapy (6 chemo+dasatinib, 4 chemo+imatinib, 8 dasatinib alone, 1 dasatinib and imatinib, 9 imatinib, 9 unknown). At transplant 35/63 (55%) were considered in 2nd CP and 28 (45%) still in BC. The majority of the pts had an identical sibling donor (42/63: 66%), 1 mismatched related, 7 matched unrelated, and 13 mismatched unrelated. Fifty-six (89%) pts had a standard conditioning regimen, 7 (11%) pts a RIC regimen and 39 (62%) had a TBI. The stem cell source was bone marrow in 33/63 (52%) pts, PBSC in 24/63 (38%) and cord blood for 6/63 (10%). Fourteen transplants were sex-mismatched (female donor for male recipient). The EBMT-Gratwohl score was low (1+2+3) for 35/63 (55%) pts, intermediate (4) for 14 pts and high (5) for 9 pts, (and 6) for 3 pts and undetermined for 2 pts. The median follow-up since transplant was 25 (range 0.43–109) months. The overall median time for neutrophil recovery (neutrophils > 0.5 109/l) was 20 days. Fourty-one (65%) pts had an aGVHD (29 grade i-II and 12 grade III-IV) with no statistical differences between stem cell sources (p=0.4 for cord vs BM and 0.58 for PBSC vs BM). The cumulative incidence of chronic GVHD (14 extensive, 10 limited) was 43% at latest follow-up, more frequent in RIC transplant. The cumulative incidence of CML relapse was 38% at 2 yrs and multivariate analysis demonstrated the significant impact on relapse of the status at transplant in favour of disease control prior to transplant HR 2.22 (1-4.93, p=0.05 and unexpectedly, no impact of BC treatment with or without TKIs prior to transplant and of other variables. The median overall survival (OS) was 22 months (see Figure 1).
The TRM was 33% at latest follow-up, and it was significantly negatively influenced by the EBMT score (p=0.0077 for scores ≥ 4), BC status at diagnosis (p=0.04). The OS was not improved when using standard conditioning regimens (p=ns), but was improved by disease status at transplant (2nd CP better than persistent BC, p=0.01) and transplant with cord blood and BM stem cell sources over PBSC (p=0.011). Multivariate analysis on OS detected as significant adverse prognosis factors EBMT score ≥5 (HR=4.63 EBMT 5, and 4.77 EBMT 6). The types of treatment of BC CML had no significant impact (with or without stratification on chemotherapy). The median progression-free survival (PFS) was 5.8 months (see Figure 2).
The PFS was not significantly improved by standard conditioning regimens but again was improved by disease control prior to transplant (2nd CP better than persistent BC, p=0.001) and with cord blood and BM stem cell sources over PBSC (p=0.057). Multivariate analysis on PFS detected as significant adverse prognosis factors EBMT score ≥5 (HR=5.82 EBMT 5, and 3.82 EBMT 6), but again, the types of treatment of BC CML prior to transplant had no significant impact.
In conclusion, this analysis suggests that OS and PFS rates are significantly improved when compared to figures from the pre-TKI era. The use of 1st or 2nd generation TKIs alone or combined to chemotherapy does not seem to influence transplant results. CML status and the EBMT score are the major factors that can significantly influence transplant outcome.
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No relevant conflicts of interest to declare.
Goal: Compare results after allogeneic HSCT for AML in CR1 in pediatric population after myeloablative conditioning regimen either based on TBI or busulfan.
Patients and Methods: Retrospective ...analysis from French registry including all consecutive patients under 18 years of age (n=131) from Dec'1979 and Oct'2004 transplanted for AML in CR1 with either sibling (n=104) or matched unrelated donor and given either multi-fractionated TBI 12Gy and cyclophosphamide 120mg/kg (TBI-Cy) or Busulfan 16mg/kg and Cyclophosphamide 200mg/kg (BuCy200). Results were analysed according to EBMT statistical analysis guidelines i.e. OS and EFS were analyzed by KM method and Log-rank test for comparison where TRM and relapse incidence were analyzed by cumulative incidence method and Gray test for comparison. Multivariate analyses were performed using proportional hazard model for the distribution of competitive risks defined by Fine and Gray.
Results: 131 patients (female: 51.5%) were included. Median age at initial diagnosis was 11y (0.5 to 17.8). Median time from diagnosis to transplantation was 4.2 months. Eighty-three patients received BuCy200 and 48 patients were transplanted after TBI-Cy. Patient subgroups were comparable for age, gender, sex mismatch, source of graft (BMT vs PBSC), donor type (geno-identical vs 10/10 matched unrelated donor vs other), cytogenetical analysis and WBC at initial diagnosis, and for donor-recipient CMV status (−/+ vs others). Both 5 year-overall and event-free survival rates appeared significantly better in BuCy200 group than in TBI-Cy group with 73.3% vs 56.1% (p=0.02) and 67+/−7% vs 38+/−9% (p=0.002), respectively. TRM incidence at day 365 was dramatically better in BuCy200 group than in TBI-Cy group with 4,7% vs 26.1% of TRM rate (p=0.002), respectively. Even though there were no statistical significant differences for both acute and chronic GVHD cumulative incidences whatever given conditioning regimen, there was a trend for obtaining lesser GVHD in BuCy200 group: day 100 grade II-IV aGVHD cumulative incidence was 13% vs 37% and 2 year extensive cGVHD was 9 vs 19% for BuCy200 and TBI-Cy group, respectively. At 5 years, there was a trend for less relapse in BuCy200 group than in TBI-Cy 16+/−3% vs 32+/−6% (p=0.09), respectively.
Conclusion: This study demonstrates the superiority of BuCy200 on TBI-Cy conditioning regimen for paediatric patients presenting with AML in CR1 and undergoing allogeneic hematopoietic stem cell transplantation from either matched related or unrelated donor. These results, obtained from a larger cohort, confirm and update those published by our group in 1994.
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Impaired linear growth has been reported in patients treated during childhood with allogeneic stem cell transplantation and fractionated total body irradiation (fTBI). The objective of this study was ...to determine the final height and body mass index (BMI) achieved. Forty-nine patients with leukemia were included and surveyed for more than 5 years. Median age at follow-up was 24.3 years (range, 18.9-35.8) and median follow-up time from allograft was 14.4 years (range, 4.5-21.9). Mean height standard deviation score (s.d.s.) at final examination (−1.1 ± 1.3,) was significantly lower than at fTBI (0.3 ± 1.2; P = .001). Final height s.d.s. was significantly correlated with age at diagnosis, age at fTBI, and target height (P = .001; P < .001; P < .001, respectively). Final height was significantly lower in children transplanted before age 5 (P = .006). Growth hormone treatment (n = 6) had only a modest effect on growth velocity. Mean BMI at follow-up was normal at 19.6 kg/m2 for boys and 21.2 for girls, but with a significant decrease since allograft only for boys (−1.2 ± 1.5 s.d.s.) (P = .003). In conclusion, final height is decreased; BMI is normal but decreased from fTBI in boys.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Rasburicase (Fasturtec), a recombinant urate oxidase, is highly effective in preventing and treating hyperuricemia in children with hematologic malignancies. We conducted a prospective, multicenter ...observational study in 174 patients at 8 pediatric hemato-oncology centers to establish whether the SFCE (Société Française de Lutte contre les Cancers et Leucémies de l'Enfant et de l'Adolescent) recommendations for the use of rasburicase in the management of pediatric patients at risk of tumor lysis syndrome (TLS) are valid in routine clinical practice. Patients were classified as being at high or low risk of TLS according to the Children's Oncology Group criteria and were treated in accordance with the SFCE recommendations. The primary end point was the number of patients requiring a higher dose of rasburicase or a longer duration of treatment than advised in the SFCE recommendations. Of the 135 patients at high risk of TLS, 27 patients received a higher dose and 35 patients received a longer duration of treatment. Some patients received treatment with rasburicase for less than the recommended duration (median 4 d for high-risk patients). One patient required hemodialysis. Only minor adjustments to the SFCE recommendations were required to ensure the optimal use of rasburicase in pediatric patients at risk of TLS.
Abstract 3460
Autoimmune diseases (AD) have been reported after haematopoetic stem cell transplantation (HSCT) and most commonly autoimmune cytopenias (AIC) are observed. Proposed risk factors are ...unrelated donor HSCT and presence of chronic graft-versus-host disease (GVHD). Use of CB cells is increasing as an alternative source of adults HSC for allotransplant however incidence and risk factors of AD after CBT have not been described. Since CB lymphocytes are immature and most of the CBT are HLA mismatched, we hypothesize a high incidence and diversity of secondary AD and. Therefore, we conducted a retrospective study in order to describe incidence, nature and risk factors for secondary AD after CBT. We include CBT recipients reported to EUROCORD up to December 2008. All centres were asked to participate to the survey even if they did not observe any case of AD after CBT. For those with AD, detailed information on diagnosis, treatment and outcome were asked. Median follow-up was 44 months (3.2-217). 42 out of 651 patients (pts) from 35 centres had developed at least one secondary AD at a median of 198 days (27-4267) after CBT. The remaining 609 pts without secondary AD served as control group (nonAD). Characteristics of both groups are given in table 1. Cumulative incidence of secondary AD after CBT was 5±1% after 3 years and 6.5±1% after 10 years. Diagnosis of secondary AD were autoimmune haemolytic anemia (AIHA) in 16, autoimmune thrombopenia (ITP) in 9, EVANS syndrome in 6, autoimmune thyroiditis in 3, glomerulonephritis in 2, Graves disease, psoriasis, psoriasis arthritis, immune neutropenia, ulcerative colitis and vasculitis in 1 patient each. Three pts developed ITP followed by AIHA. Median time to develop a AIC was 180 days (27-4267) and non-hematological AD was 322 days (70-1117), respectively (p=0.13). At onset of AD, 3 pts had acute GvHD, 6 chronic GvHD and in 10 pts an infection. In multivariate analysis adjusted for differences between the two groups, the following factors were associated with higher incidence of secondary AD: 1) age<10 years (8.8% vs 3.6%, HR:2.5; p=0.01); 2) CBT after 2006 (8.5% vs 3.4%, HR:2.23; p=0.01) and 3) non-malignant haematological disorders (12.5% vs 4.2%, HR 2.5, p=0.008). There was a trend of higher incidence of AD after unrelated compared to related CBT (6.7% vs 1.6%, HR: 3.71, p=0.07). Number of HLA disparities, cell dose, single or double CBT or use of ATG were not associated with incidence of AD. At last assessment, 317 of overall 651 pts and 35 of 42 pts with secondary AD were alive, respectively. Of 32 pts with AIC, all received immunosuppression as first line therapy (systemic steroids associated or not to CsA, cyclophosphamide) and in 14 ptsrituximab was added. Of those 14 pts receiving anti-CD20, 8 had a complete remission (CR), 3 a partial remission (PR) and 3 did not respond (died due to haemorrhage or infection associated to AIC). Of the 18 remainders 9 had a CR, 5 a PR and 4 did not respond (1 died). Among 6 patients without CR to first line treatment with rituximab, 1 responded to a second line with rituximab, 2 were alive after a different treatment and 3 died. Twenty-five patients with AIC were alive at last follow-up. Of 10 patients with other AD (non AIC), 7 were treated with immunosuppressive treatment (systemic steroids, CsA, tacrolimus), 2 with replacement therapy (thyroid hormone) and 1 treatment was not given (Graves disease); of those 9 patients treated, 7 achieved a CR and 2 a PR. All pts with non-AIC were alive at last follow-up. In conclusion, AD occur in more than 6% of 651 pts after CBT. Most often AIC (n=32) was diagnosed and it is associated with morbidity and mortality (7 pts died of 32). Younger age at transplantation and CBT for non-malignant disease are important risk factors for secondary AD.
Table 1:Characteristics of pts developing AD or not (nonAD)Pts characteristicsAD ptsnonAD ptsPfemale sex36%45%age at HSCT2.23 (0.2–43.24) years10.7 (0.11–66.5) years0.0001year of HSCT2006 (95–08)2006 (92–08)0.04Type of donorunrelated95%90%0.26Indication for HSCT (n)ALL10184AML2150MDS467AA552SCID651CML324NHL021Hemoglobinopathy015Histiocytosis214Metabolic diseases919others111GraftSingle cord85%77%0.25Double cord14%23%HLA compatibility5/6+6/668%48%0.02ConditioningRIC80%73%0.34TBI20%43%0.0004Serotherapy73%74%0.86Host CMV statuspositive45%58%0.11
No relevant conflicts of interest to declare.
Purpose: Objective was to assess indication, feasibility and efficacy of double allograft with reduced intensity conditioning.
Patients and Methods: All double allogeneic hematopoietic stem cell ...transplantation (AHSCT) after reduced intensity regimen reported to Promise database were retrospectively studied. Because of the initial lack of clinical and biological data in the Registry, all centers were contacted to improve the database.
Results: 66 double mini-allografts were realized in 25 french transplant centers. At this time, 35 mini-allografts presented complete informations corresponding to 14 transplant centers. Diagnosis was LAM (n=15), aplasic anemia (n=5), MDS and/or MPS (n=5), LAL (n=2), Myeloma (n=2), ovarian cancer (n=1), LNH (n=2), LLC (n=1), LMC (n=1) and Hodgkin lymphoma (n=1). Median age at first transplantation was 49.3 years 12.75–64.9 with a median time from diagnosis to first transplant of 22.9 months 3.6–163.7. Disease status before transplant was progression (n=5), partial response (n=3), complete response (n=18), induction failure (n=2) and chronic phase (n=2). The 5 aplasic anemias were not evaluable for this status. Most patients received fludarabine (n=31), SAL (n=22), busulfan (n=15) based regimen. Graft source was PBSC in 74% of grafts. Median age of donor was 42 years 4–68. HLA relation of donor with patient was identical sibling (n=22), match unrelated (n=10) or mismatch unrelated (n=3). Second allograft indication was relapse (n=22), lost of graft (n=7), no engraftment (n=5) or residual disease (n=1). Eihgty percents of patients underwent a different conditioning. It was similar for only 7 patients (same n=1, increase SAL dose n=1, SAL addition n=2, dose reduction n=1). Median time between the two allografts was of 7.6 month 1.1–61.0. Source of stem cells and donor were changed in 13.6% and 37% of allograft respectively. The median time to reach an absolute neutrophil count of 0.5 × 109/l and platelet count of 50 × 109/l was shorter after second allograft (21.4 days 12.4–759.5 versus 16.8 days 6.2–105.4 and 16.3 days 9.3– 71.3 versus 14.26 3.1–83.7) with no significant difference. Overall incidence of acute GvH was similar after the two allografts (34% versus 43%). However, acute GvH grade III–IV proportion seems to be higher after second allograft (8% versus 40%). Similarly, proportion of chronic GvH was 23% versus 27% with an increase of extensive GvH after second allograft (50% versus 66%). Response was improved by second allograft in five patients (15%) and allowed to engraftment in 3 patients (7%). To date, 8 patients are still alive. 14 patients died from progression and 11 of TRM (3 multiple organ failure, 5 respiratory failure, 2 fungal infection and 1 rejection) giving a TRM proportion of 31%. With a median follow-up of 57.1 months 21.9–128.8, the median overall survival (OS) was of 24 months 2–71. Delay greater than 7.7 months and same source of stem cell between two mini-allografts improved OS (50 months versus 9 months, p = 0.0085 and 28 months versus 14 months, p=0.11).
Conclusions: Our preliminary results suggests response improvement after double AHSCT with reduced conditioning. However, TRM proportion was high.
A teenager was admitted with an iron-deficiency anemia. The gastroscopy found an atrophic body gastritis, which revealed a pernicious anemia. This diagnosis is rare in paediatric patients, the ...frequency of pernicious anemia increasing with age. Iron-deficiency anemia is mainly described in young people.
Short-term intensive chemotherapy regimens have substantially improved the prognosis of pediatric patients with Burkitt lymphoma (BL), which now has an excellent overall outcome. However, central ...nervous system (CNS) involvement at diagnosis remains a poor prognostic factor, and progressive or relapsed disease in the CNS is associated with even worse outcomes. We report 3 boys aged 4, 7, and 12 years treated under the French Société Française d'Oncologie Pédiatrique LMB 89/96 protocols who presented, respectively, with CNS-/bone marrow+ stage-IV BL; CNS+ stage-IV BL; and stage-I BL. Each experienced an isolated CNS relapse, which was treated with CNS-directed salvage chemotherapy. All 3 are alive after 11 years of median follow-up, indicating that this chemotherapy regimen can be curative in pediatric BL with isolated CNS relapse.
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