scholarly journals Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) with Different Intensity Conditioning Regimens in Children with Very High Risk Acute Lymphoblastic Leukemia (VHR ALL): A Single-Center Experience

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2050-2050
Author(s):  
Elena Vladimirovna Semenova ◽  
Olesia V Paina ◽  
Zhemal Zarifovna Rakhmanova ◽  
Polina Valerievna Kozhokar ◽  
Anastasia S Frolova ◽  
...  
Keyword(s):  
High Risk ◽  
Performance Status ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Unrelated Donor ◽  
Reduced Intensity Conditioning ◽  
Myeloablative Conditioning ◽  
Hematopoietic Stem ◽  
Very High ◽  
Reduced Intensity

Background: Allo-HSCT with myeloablative conditioning (MAC) has traditionally been performed in patients with ALL and has been associated with significant transplant-related morbidity and mortality. Reduced-intensity conditioning (RIC) is used in patients not eligible for conventional conditioning therapy due to poor performance status and severe toxic complications after previous chemotherapy. RIC is a well-established treatment strategy in adult patients with comorbidities or in elderly patients. In contrast to the adults, the RIC pediatric experience is still sparse. The aim: to compare efficacy of reduced intensity conditioning (RIC) and myeloablative conditioning (MAC) for allo-HSCT in children suffering from very high risk (VHR) ALL. Patients and methods: This was a retrospective analysis performed in 233 patients (pts) with ALL (age - from 4 month till 18 y.o. (mediana 11 y.o.)), who received allo-HSCT at R.M. Gorbacheva Memorial Institute of Children Oncology, Hematology and Transplantation between 12/2000 and 12/2017. MAC (busulfan or treosulphan containing) was used in 159 pts: 1st CR - 26 pts, 2nd CR -57 pts, 3rd or 4th CR 23 - pts, relapse -53 pts. Allo-HSCT with RIC was performed in 74 pts: 1st CR - 14 pts, 2nd CR -29 pts, 3rd or 4th CR - 12 pts, relapse -20 pts. RIC consisted of fludarabine (30 mg/m2/d x 5 days) + melfalan (70 mg/m2/d x 2 days) or fludarabine (30 mg/m2/d x 5 days) + busulfan (4 mg/kg/d x 2 days). The disease status was not different between groups (p=0.674) Indication for RIC allo-HSCT was poor performance status (Lanskoy/Karnovsky<70%), organ dysfunction due to previous therapy or infectioous complications at the moment of allo-HSCT. Allo-HSCT from matched related donor was performed in 41 pts, from matched unrelated donor - in 131 pts, haploidentical - in 61 pts. Post-transplant Cy was included in GVHD prophylaxis regimens in 102 pts (44%). Results: Median follow-up was 5 years for МАС, 4.5 years for RIC. In both groups the median time to neutrophil engraftment >=0,5x109/l was D+18 (range D+8-48). Transplant engraftment was observed in 64 pts (86%) after RIC and 150 pts (93%) after MAC (p=0,224). OS pts after RIC allo-HSCT performed in 1 CR 70% and after MAC - 85% (p=0,043), in 2 CR 56% after RIC and 49% after MAC (p=0,436), in 3 or 4 CR 34% after RIC and 25% after MAC (p=0,394). OS in patients with active disease was 16% in RIC-group and 18% in MAC-group (p=0,432). The transplant-related mortality rate was 18% after RIC and 20% after MAC (p=0,40). Risk of relapse was 37% after RIC and 42% after MAC (p=0,39). Acute GVHD II-IVgr developed in 32% pts after RIC and 33% after MAC (p=0,883), early infections were diagnosed in 63% in RIC-group, and 59% in MAC-group (p=0,356). Early toxic complications were observed (CTC): mucositis III-IV gr in 13% pts after RIC and in 54% pts after MAC (p=0,001), nephrotoxicity in 7% pts and in 21% pts (p=0,042), hepatitis gr II-III in 24% pts and in 57% pts, respectively (p=0,034), neurological complications in 22% pts and 42% pts, resp. (p=0,046). Conclusion: RIC allo-HSCT of VHR ALL in 2,3 or 4 CR pts ≤ 18 y.o. is effective and comparable with MAC allo-HSCT. Early toxic complications after RIC were less frequent. Possibly, the use of RIC can maintain efficacy while minimizing regimen-related toxicity in children who have undergone previous intensive treatment. Disclosures Moiseev: Pfizer: Other: Travel grants; BMS: Other: Travel grants; MSD: Other: Travel grants; Novartis: Consultancy, Honoraria, Other: Travel grants, Speakers Bureau; Celgene: Consultancy, Other: Travel grants; Takeda: Other: Travel grants.

scholarly journals Risk Factors for Overall Survival in Children with High Risk Acute Myeloid Leukemia (HR AML) after Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) with Different Intensity of Conditioning Regimens

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 29-29
Author(s):  
Elena Vladimirovna Semenova ◽  
Olesia V Paina ◽  
Zhemal Zarifovna Rakhmanova ◽  
Polina Valerievna Kozhokar ◽  
Anastasia S Frolova ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Performance Status ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Hematopoietic Stem ◽  
Factors Influencing ◽  
Remission Status ◽  
Conditioning Regimens ◽  
The Moment

Background: Traditionally, children with AML undergo аllo-HSCT with myeloablative conditioning (MAC). It is known that MAC is associated with significant transplant-related morbidity and mortality. Reduced-intensity conditioning (RIC) is used in patients not eligible for conventional conditioning therapy due to poor performance status and severe toxic complications after previous chemotherapy. RIC is a well-established treatment strategy in adult patients with comorbidities. But there is no conclusive evidence to support efficacy of RIC allo-HSCT in children suffering from different malignant diseases including AML. The aim: To compare efficacy of different intensity conditioning regimens in children with high risk (HR) AML (according to AML-BFM protocols 1998 and 2004) and to identify factors which have a prognostic significance for overall survival (OS). Patients and methods: Retrospective analysis was performed in 192 patients (pts) with AML (median age of 10 years (0.5-18 y.o.), who received allo-HSCT at R.M. Gorbacheva Research Institute between 08/2000 and 09/2019. MAC (busulfan- or treosulfan-based) were used in 109 pts: 1st CR - 46 pts (MRD+ n=11), 2nd CR - 18 pts, 3rd CR - 1 pt, relapse - 44 pts. Allo-HSCT with RIC were performed in 83 pts: 1st CR - 32 pts (MRD+ n=13), 2nd CR -19 pts, 3rd CR - 4 pts, relapse -28 pts (p=0,674). RIC consisted of fludarabine (30 mg/m2/d x 5 days) + melphalan (70 mg/m2/d x 2 days) or fludarabine (30 mg/m2/d x 5 days) + busulfan (4 mg/kg/d x 2 days). Indication for RIC allo-HSCT was poor performance status (Lansky/Karnofsky score ≤70%), or organ dysfunction due to previous therapy, or infectious complications at the moment of allo-HSCT. Allo-HSCT from matched related donor was performed in 30 pts (16%), from matched unrelated donor - in 98 pts (51%), haploidentical - in 64 pts (33%) and the donor distribution was not different between groups (p=0,878). Post-transplant Cy was included in GVHD prophylaxis regimens in 102 pts (53%). OS were estimated using Kaplan-Meier curves. Univariate analyses were performed using the log rank test for OS, Grey test for cumulative incidences. Multivariate analyses were performed using the Cox proportional-hazard model. Results: Median follow-up was 5 years for МАС, 4.5 years for RIC. In both groups the median time to neutrophil engraftment &gt;=0,5x109/l was D+16 (range D+8-52). Engraftment was observed in 67 pts (81%) after RIC and 94 pts (86%) after MAC (p=0,231). OS after RIC allo-HSCT in the 1st CR was 76% and after MAC - 68% (p=0,014), in 2nd CR 50% after RIC and 54% after MAC (p=0,058), in advanced disease 14% after RIC and 16% after MAC (p=0,394). The transplant-related mortality rate was 19% after RIC and 22% after MAC (p=0,546). Risk of relapse was 28% after RIC and 26% after MAC (p=0,456). Factors influencing OS after MAC were: 1) Remission status at the moment of allo-HSCT (р=0.001); 2) Presence of aGVHD grade I-II (р=0,005); 3) Relapse or MRD+ status after allo-HSCT (р=0.012); 4) Lansky score &gt;70% (р=0,024). Factors influencing OS after RIC were: 1) Remission status at the moment of allo-HSCT (1st remission) (p=0,001); 2) Lansky score &gt;70% (р=0,004). Conclusion: The effectiveness of RIC and MAC is comparable in children with HR AML, but RIC demonstrated better results in 1st CR. The presence of I-II grade aGVHD had positive effect in MAC. Factors influencing OS in both groups were disease status at the moment of allo-HSCT and performance status before allo-HSCT The use of RIC can be effective in patients, especially those who have undergone allo-HSCT in the 1st remission, while minimizing regimen-related toxicity in children who have undergone previous intensive treatment. Multicenter studies are warranted, especially for patients in the first CR, where long-term complications are of most importance. Disclosures No relevant conflicts of interest to declare.

Efficacy of Reduced Intensity Conditioning (RIC) with FLU-BU-ATG and Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for Pediatric ALL.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2314-2314 ◽  
Author(s):  
Reggie Duerst ◽  
David Jacobsohn ◽  
William T. Tse ◽  
Morris Kletzel
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Chronic Gvhd ◽  
High Dose ◽  
Reduced Intensity Conditioning ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Pediatric All ◽  
Very High ◽  
Reduced Intensity

Abstract Reduced Intensity Conditioning (RIC) regimens prior to allogeneic HSCT have gained acceptance in the treatment of adults with myelodysplasia, leukemia and multiple myeloma. RIC reduces the risk for regimen related morbidity and mortality enabling patients with pre-existing medical conditions that would have been precluded from allogeneic HSCT to attempt a curative approach. The resilience of pediatric patients (pts) following high-dose conditioning regimens and the concern that ALL cells are inherently more resistant to a graft-vs-leukemia effect have limited accrual of pediatric ALL pts to RIC protocols despite the potential benefit for reduced long-term morbidity. We report the experience of 10 pediatric ALL pts (6 M, 4 F, median age 9.5 years) treated for recurrent ALL with RIC and allogeneic HSCT. A uniform RIC regimen comprised of fludarabine, 30 mg/m2 for 6 consecutive days (days −10 through −5), followed by intravenous busulfan, 0.8 – 1 mg/kg for 8 doses or targeted AUC 4000 μMol*min for 2 doses (days −5 and −4) and equine ATG, 40 mg/kg or rabbit ATG, 2 mg/kg for 4 days (days −4 through −1) was administered. Pts with prior CNS involvement received whole brain (2400 cGy) and spinal (1800 cGy) irradiation immediately prior to the RIC. Stem cell sources included 7 unrelated donors and 3 matched sibs. 9 of 10 stem cell donations were peripheral blood stem cells (PBSC). The median cell doses infused were 6.5 x 108 MNC/kg and 4.2 x 106 CD34+ cells/kg. Graft-versus-host disease (GVHD) prophylaxis was cyclosporin A (CsA) alone in 5 patients, CsA and mycophenolate mofetil in 5 pts. Growth factor support was not used. Each of the pts had at least two very high-risk features--prior HSCT (n = 6), CR > 3/refractory disease (8), prior CNS disease (6), Ph+ (2), pre-exisiting neurologic (1) or cardiac (1) dysfunction or aspergillous infection (1). Full donor chimerism was achieved in 9 of 10 with a median time to reach an ANC >500/μl of 16 days (range 11–62) and an unsupported platelet count > 20,000/μl was achieved in 8 of 10 at a median of 25 days (15–67). 2 pts developed Gr IV acute GVHD, 2 of 5 pts surviving more than 100 days developed chronic GVHD. Only 3 patients have relapsed: 1 refractory T-ALL pt recurred day +27 and 2 Ph+ pts had a molecular relapse day +61 and +196. The latter pt is in subsequent continuous molecular remission for over 1 year on imatinib therapy. 6 pts have died, 5 in the first 100 days of HSCT from complications of GVHD (2), relapse (1), pulmonary failure (in 1 pt S/p 3 prior allogeneic HSCT) and PTLD (1). 1 pt succumbed from complications of chronic GVHD day +756. The RIC regimen and supportive care are primarily an outpatient experience. During the first 30 days post HSCT, pts spent an average of only 9 days in hospital (23 of the first 100 days). Despite very high-risk features, 4 of 10 pts survive (3 CCR) at a median of 500 days post HSCT. Thus, RIC and allogeneic HSCT also offers promise for efficacy in pediatric ALL.

Fludarabine Is Superior to Cladribine When Added to Busulfan and Low Dose TBI as Reduced Intensity Conditioning for Allogeneic Hematopoietic Cell Transplantation (HCT): A Prospective Randomized Trial.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1825-1825
Author(s):  
M. Markova ◽  
Juliet N. Barker ◽  
John E. Wagner ◽  
Jeffrey S. Miller ◽  
Mukta Arora ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Cell Transplantation ◽  
Cumulative Incidence ◽  
Unrelated Donor ◽  
Reduced Intensity Conditioning ◽  
Purine Analogues ◽  
Hematopoietic Stem ◽  
Platelet Recovery ◽  
Reduced Intensity

Abstract Purine analogues have been combined with alkylator/irradiation as immunosuppressive and anti-tumor conditioning prior to allogeneic hematopoietic stem cell transplantation (HCT) though differing purine analogues have not been compared. We prospectively tested Fludarabine (F) 40 mg/m2/d x 5d vs. Cladribine (C) 10 mg/m2/d x 5d plus Busulfan (Bu) (2mg/kg q12h x 2d) and total body irradiation (T) 200cGy followed by cyclosporine and mycophenylate mofetil in 19 recipients of matched sibling peripheral blood stem cell and 13 unrelated donor (URD) marrow HCT. Patients in each randomly assigned cohort [FBuT vs. CbuT] were similar in age (median 52 years in both groups), diagnosis (leukemia/MDS 38 vs. 31%; lymphoid malignancy 57 vs 69%), extensive pre-HCT therapy (56 vs. 63%), high risk disease status (81 vs. 93%) and Karnofsky (median 90 in each)[all p= NS] though fewer FBuT were URD recipients 25% vs. CBuT 56%, p=0.07. Engraftment was prompt in both groups (median 11 vs. 12 days), but the cumulative incidence of neutrophil engraftment was 75% (95% C.I. 54–96%) using CBuT vs. 100% with FBuT (p<0.01) and randomization was halted. Platelet recovery was prompt (median FBuT 18 vs CBuT 24 days) and after FBuT 75% (95% C.I. 49–100) vs. CBuT 69% (43–95) recovered platelets > 50,000/μL by day +180, p=0.19. The cumulative incidence of GVHD after FBuT vs. CbuT was similar (acute grade II/IV 56 vs. 69%, p=0.26) and (chronic 50 vs. 31%, p=0.27). Transplant related mortality at day +180 was also similar [FBuT 25% (4–46) vs. CbuT 38% (14–61), p=0.47]. Survival was equivalent: at 1 year 50% in each group; at 3 years FBuT 25% vs. CBuT 38%, p=0.55. Multivariate analyses adjusted for age, donor type, diagnosis and stage as well as conditioning regimen showed lower relative risk (RR) of engraftment with CBuT (RR 0.6 (95% C.I. 0.2–1.3) p=0.16) and with URD RR 0.4 (0.2–1.0) p=0.04). RR of Platelet recovery was equivalent with FBuT (RR 0.7 (0.3–1.7) p=0.45) but inferior with URD (RR .16 (.05–.5) p<0.01). RR of GHVD II/IV similar with FBuT RR 1.1, p=0.95, but more frequent with URD RR 2.0, p=.2 and high risk status patients (RR 4.5, 1.5–13.5, =<0.01). Prevalence of remission (CR or PR) at 18 months was high and was similar in both groups (FBuT 100% vs CBuT 86%, p=NS). These data suggest that older patients with advanced hematologic malignancies can achieve satisfactory post-transplant outcomes using either of these combination/reduced intensity conditioning regimens. Fludarabine may be superior to cladribine as a component of pre-HCT conditioning with Bu/TBI due to reduced risks of graft failure. Further modifications of the regimen may confirm universal engraftment with even lower peri-transplant morbidity.

Age Does Not Predict Outcomes For Elderly Patients With Myelodysplastic Syndromes Undergoing Hematopoietic Stem Cell Transplantation With Reduced-Intensity Conditioning

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2147-2147
Author(s):  
Gregory A. Abel ◽  
Haesook T. Kim ◽  
Philippe Armand ◽  
Corey S. Cutler ◽  
Joseph H. Antin ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Hematopoietic Stem Cell Transplantation ◽  
Older Patients ◽  
Prognostic Score ◽  
Reduced Intensity Conditioning ◽  
Hematopoietic Stem ◽  
Gvhd Prophylaxis ◽  
Very High ◽  
Reduced Intensity

Background The National Care Determination for allogeneic hematopoietic stem cell transplantation (allo HSCT) for the treatment of myelodysplastic syndromes (MDS) stated that there is an absence of convincing evidence that allo HSCT improves health outcomes. A prospective data-gathering trial sponsored by the CIBMTR is ongoing; however, until such results are available, retrospective methods specifically comparing older populations are illustrative. Methods We analyzed outcomes for older patients with MDS undergoing HSCT with reduced intensity conditioning (RIC) at the Dana-Farber/BWH with uniform conditioning and graft versus host disease (GVHD) prophylaxis regimens from 2001 to 2011. Patients with CMML were excluded. Those aged 60-65, and those ≥ 66 were compared to assess overall survival (OS), progression free survival (PFS), and other HSCT-related outcomes. Aiming to build a better prognostic score using its significant components, we also assessed the association of the IPSS-R at transplantation as well as each of its components with OS, and fit multivariable Cox regression models with the new prognostic score as well as age. Results We identified 67 patients aged 60 or older who underwent RIC HSCT for MDS. All patients received fludarabine and intravenous busulfan as conditioning, and peripheral blood stem cells. GVHD prophylaxis included tacrolimus/rapamycin +/- MTX. The median age was 64 (60-74) years, and the majority (64%) had unrelated donors. 60% had advanced MDS (IPSS-R high risk or very high risk), 46% had poor risk cytogenetics, and 67% had high or very high disease risk index (DRI). The median age for the 60-65 group was 63; the median age for the ≥ 66 group was 69. We found no significant differences in PFS or OS by age category, as shown below (also see figure): In addition, rates of 6-month grade III-IV GVHD (p=.45) and 2-year incidence of cGVHD (p=0.78) did not significantly differ. The IPSS-R performed only modestly in predicting 4-year OS for this older cohort (p=.20); however, a new 3-level score (including collapsed cytogenetic categories, dichotomous platelet count [ ≥ 50 or < 50], percent blasts in marrow and dichotomous ANC) performed better (p=.008; see figure). In two multivariable models, one that included the IPSS-R and another that included the new score, age was not a significant predictor of OS (p=.78 and .77 respectively). Conclusions Our data suggest that age alone should not limit availability of RIC HSCT for patients with MDS, as older patients in our elderly cohort faired similarly to younger ones with respect to important HSCT-related outcomes. Our new prognostic score, if validated, may be able to help risk-stratify patients. Finally, continued efforts are needed to reduce relapse in high-risk elderly MDS patients. Disclosures: No relevant conflicts of interest to declare.

Reduced Intensity Conditioning Compared With Myeloablative Conditioning Using Unrelated Donor Transplants in Patients With Acute Myeloid Leukemia

2009 ◽  
Vol 27 (27) ◽  
pp. 4570-4577 ◽  
Author(s):  
Olle Ringdén ◽  
Myriam Labopin ◽  
Gerhard Ehninger ◽  
Dietger Niederwieser ◽  
Richard Olsson ◽  
...  
Keyword(s):  
Conditioning Regimen ◽  
Multivariable Analysis ◽  
Unrelated Donor ◽  
Reduced Intensity Conditioning ◽  
Myeloablative Conditioning ◽  
Peripheral Blood Stem Cells ◽  
Hematopoietic Stem ◽  
Blood Stem Cells ◽  
Total Body ◽  
Reduced Intensity

Purpose Reduced intensity conditioning regimen (RIC) is increasingly used in hematopoietic stem cell transplantation (HSCT). Unrelated donor (UD) transplants have more complications. We wanted to examine if RIC is a valid treatment option using UD in acute myeloblastic leukemia (AML). Patients and Methods Between 1999 and 2005, 401 patients with AML were treated with RIC and 1,154 received myeloablative conditioning (MAC), using UD and reported to the European Group for Blood and Marrow Transplantation Registry. Patients < and ≥ 50 years of age were analyzed separately. Results Patients receiving RIC were older, received transplants more recently, received peripheral blood stem cells more frequently, and were treated with total-body irradiation less often. In multivariable analysis, in patients younger than 50 years of age, nonrelapse mortality (NRM) was similar using RIC (hazard ratio [HR], 0.85; P = .41), relapse was increased (HR, 1.46; P = .02) and leukemia-free survival (LFS) was the same (HR, 0.88; P = .28), as compared with MAC. In patients ≥ 50 years of age, NRM was decreased in the RIC group (HR, 0.64; P = .04), relapse probability was not significantly different (HR, 1.34; P = .16) and LFS was similar (HR, 1.04; P = .79) compared with MAC. Conclusion RIC-UD transplants are associated with higher relapse in AML patients younger than 50 years of age and decreased NRM in those ≥ 50 years compared with MAC-UD. LFS was similar after both conditioning regimens, regardless of age. Therefore, RIC-UD extend the use of allotransplants for elderly patients and strategies that decrease relapse should be considered mainly in younger patients with AML.

Fractionated gemtuzumab ozogamicin combined with intermediate-dose cytarabine and daunorubicin as salvage therapy in very high-risk AML patients: a bridge to reduced intensity conditioning transplant?

2016 ◽  
Vol 96 (3) ◽  
pp. 363-371 ◽  
Author(s):  
Etienne Paubelle ◽  
Sophie Ducastelle-Leprêtre ◽  
Hélène Labussière-Wallet ◽  
Franck Emmanuel Nicolini ◽  
Fiorenza Barraco ◽  
...  
Keyword(s):  
High Risk ◽  
Salvage Therapy ◽  
Gemtuzumab Ozogamicin ◽  
Reduced Intensity Conditioning ◽  
Very High ◽  
Reduced Intensity ◽  
Intermediate Dose

Phase II Study of Gemtuzumab Ozogamycin (GO) and Cytarabine (ARA-C) in Patients with High Risk MDS and AML..

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4723-4723
Author(s):  
Peter Kang ◽  
Karen Seiter ◽  
Delong Liu ◽  
Muhammad Arshad ◽  
Anila Qureshi ◽  
...  
Keyword(s):  
High Risk ◽  
Performance Status ◽  
Poor Performance ◽  
Complete Response ◽  
Lung Damage ◽  
Poor Performance Status ◽  
High Cumulative Dose ◽  
History Of ◽  
M 12 ◽  
To Receive

Abstract To evaluate the efficacy of GO + ara-c in high risk pts, we treated 22 pts with MDS (10) and AML (12) with cytarabine 100 mg/m2/d x 7 d and GO 9 mg/m2 x 1 on d 4. Pts with MDS were eligible if they had [1] RAEB-1 and either hgb &lt; 8 gm/dl, platelet &lt; 50,000/mm3, neutrophils &lt; 1000/mm3, or cytogenetics other than 5q-, 20q-, -y, or normal, [2] RAEB-2, or [3] CMML. Pts with AML (newly diagnosed or relapsed) were eligible if they were ineligible for anthracycline-based therapy (poor performance status: 2 pts; low ejection fraction or high cumulative dose of anthracyclines: 6 pts, both reasons: 4 pts). The median age was 66, M:12, F:10. Diagnoses: RAEB-1: 4, RAEB-2: 5, CMML: 1, AML, newly dx’d: 7, AML relapsed: 5. Cytogenetics were high risk: 10, intermediate risk: 11 pts, low risk: 1 pt. Overall, 18% had a complete response (CR) after one cycle of therapy. Three pts (14%) had a partial response (PR), of which one had a CR after a second course of therapy. Of the pts with AML: CR: 2/12, PR: 2/12, Failure (F): 5/12, Toxic Death (TD): 3/12. For pts with MDS: CR: 2/10, PR: 1/10, F: 5/10, TD: 2/10. Toxicities included neutropenic fever/sepsis, mucositis, diarrhea, increased LFTs, hemorrhage. One pt with a history of ABVD and RT to chest for HD developed direct pulmonary toxicity due to chemotherapy (diffuse pulmonary infiltrates, biopsy proven toxic lung damage). Although overall response rate is modest, some pts had remarkable responses: One pt with RAEB-1, transfusion dependent and multiple high risk cytogenetics (−5, −7, multiple others) remains in CR (including cytogenetic CR) 7 months post treatment. A second pt with RAEB-1, transfusion dependent and multiple high risk cytogenetics (−5, −7, multiple others) had a PR after one course, but was unable to receive further chemotherapy due to toxicity. The latter pts suggest that this regimen should be studied further in pts with MDS, poor risk cytogenetics and low blast counts.

Excessive Rate of Late Infections and Treatment Related Mortality Associated with the Use of Alemtuzumab in Reduced Intensity Conditioning for Allogeneic Hematopoietic Stem Cell Transplantation: Results of a Prospective Trial.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2230-2230
Author(s):  
Munira Shabbir ◽  
Luciano J Costa ◽  
Christine Schaub ◽  
Carrie Maxwell ◽  
Theo Fouts ◽  
...  
Keyword(s):  
Hematological Malignancies ◽  
Acute Gvhd ◽  
Infectious Complications ◽  
Unrelated Donor ◽  
Reduced Intensity Conditioning ◽  
Myeloablative Conditioning ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Group A ◽  
Related Mortality

Abstract Abstract 2230 Poster Board II-207 Background: Reduced intensity conditioning (RIC) for allogeneic hematopoietic stem cell (HSC) transplantation is a well established therapy for patients with advanced hematological malignancies who are not suitable candidates for fully myeloablative conditioning. The use of alemtuzumab as part of RIC has been associated with decrease in incidence and severity of graft versus host disease (GVHD), particularly in unrelated donor transplants. Methods: This is a single center, prospective study. Patients with relapsed or refractory hematological malignancies who were not candidates for fully myeloablative conditioning regimens received an non-alemtuzumab (nA) containing RIC regimen or an alemtuzumab-containing regimen (A) based on the use of a matched sibling or an allele-matched unrelated donor, respectively. Patients in the nA group were conditioned with either Fludarabine 30mg/m2/day for 5 days and total body irradiation 200cG or Fludarabine 25mg/m2/day for 5 days and Melphalan 70mg/m2/day for 2 days. Patients in the A group received alemtuzumab 20 mg/m2/day for 2 days, Fludarabine 30mg/m2/day for 5 days and Melphalan 70mg/m2/day for 2 days. All patients received peripheral blood HSC grafts. Prophylaxis against graft versus host disease with cyclosporine and mycophenolate mofetil as well as infectious disease prophylaxis and supportive care guidelines were standard across both groups. Results: From January 2003 to March 2009, 56 patients were enrolled in the study and 50 patients who actually received a HSCT are the subject of this analysis. Twenty nine patients were in group nA and 21 in group A. Median age of the patients in the entire cohort was 55 years (range 14-65). Eighteen patients had AML, 12 NHL, 8 MDS, 6 CML, 3 CLL and 3 MM. Twenty-three patients were considered to be at high-risk for post transplant relapse (45% of group nA vs. 47% of group A, P= 0.84). All patients in group nA had hematological engraftment while 2 patients in A (9.5%) failed to engraft. Despite the fact that all patients in group A received a transplant from an unrelated donor, the incidence of severe (grades C or D) acute GVHD was significantly higher in group nA (20.7% vs. 0%, P=0.03). Day 100 mortality was similar between the 2 groups (20.7% for nA vs 33.1% for A, P=0.31). Cumulative incidence of progression did not differ between the two groups (P=0.7) while the cumulative incidence of treatment related mortality was higher in group A (P=0.02, Figure 1). Both median overall survival (OS) (44.1 vs. 5.3 months; P=0.01, figure 2) and progression-free survival (PFS) (8.7 vs 5.3 months, P= 0.02) were superior in group nA. Cox regression analysis including conditioning regimen, age and risk of post-transplant relapse showed that conditioning with alemtuzumab was the only variable significantly associated with inferior OS (RR 2.8, P=0.009) and PFS (RR 2.42, P= 0.01). Group A had a higher incidence of late (after Day 100) infectious complications resulting in death (43% vs.10%, p=0.01). Conclusion: Even though alemtuzumab-based RIC in unrelated HSCT has a protective effect against acute GVHD and risk of D+100 TRM comparable with non-alemtuzumab containing RIC regimens in related donor transplant, its beneficial effect is overcome by excessive late infectious complications. Disclosures: Fouts: Genzime: Consultancy.

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