Quantitative Real-Time PCR Detection of Wilms' Tumor Gene (WT1) Transcript in Autologous Peripheral Blood Stem Cell (PBSC) Products Predict the Risk of Acute Myeloid Leukaemia (AML) Relapse After Autologous Transplantation (ASCT).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4690-4690
Author(s):  
Carlo Messina ◽  
Cristina Tresoldi ◽  
Alessandro Crotta ◽  
Michela Tassara ◽  
Simona Malato ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Complete Remission ◽  
Preliminary Data ◽  
Peripheral Blood ◽  
Autologous Transplantation ◽  
Conditioning Regimen ◽  
Rt Pcr ◽  
Free Survival ◽  
Transcript Levels ◽  
Increased Risk

Abstract Abstract 4690 Introduction when allogeneic transplantation is not feasible, ASCT is an alternative option as post-remission therapy for patients (pts) with AML, as it can prolong their disease-free survival (DFS). Relapse is the main cause of AML treatment failure after initial complete response; AML relapse after ASCT is partly due to contamination with leukemic blasts of the PBSC products, although neither morphological nor genetic evidence of disease are detected in the bone marrow before leukapheresis. Thus, identification and quantification of a reliable minimal residual disease (MRD) marker in the collected PBSC could be relevant in determining the relapse risk after ASCT. The WT1 gene is overexpressed in leukemic blasts of most AML cases; several studies have shown that quantification with RT-PCR of WT1 in the bone marrow and peripheral blood of AML pts in complete remission has prognostic value. We have determined the WT1 transcript levels in autologous PBSC of AML pts autografted for complete remission (CR) consolidation; preliminary results and data interpretation are here presented. Aim to evaluate quantitative WT1 transcript levels in autologous PBSC collections and to compare results with outcome in AML patients who received an ASCT as consolidation of CR, at our Institute. Patients and Methods 9 pts, period 06/2006-03/2009, median age 68 years (range 41-76). At diagnosis cytogenetic prognostic risk was intermediate for all pts. All pts were in morphological and genetic CR at the time of PBSC collection and before ASCT. Eight patients were in first and 1 in second CR. PBSC collection by leukapheresis (COBE Spectra cell separator): median count of CD34+ 9.75 ×106/kg (3.79-32). Conditioning regimen: Treosulfan 30 mg/sqm, Fludarabine 150 mg/sqm and Cytarabine 5 g/sqm. Median count of CD34+ cells infused: 5×106/kg (range 3.3-8.5×106/kg). RT-PCR quantification of WT1 transcript was performed using TaqMan technology starting from 1 μg of RNA extracted from mononucleated cells of fresh (4) or cryopreserved (5) PBSC samples. The housekeeping gene ABL was used as the control gene for these quantifications with WT1 level being normalised to 104 copies of ABL per sample. We used the Mann-Whitney-U-test to determine if median WT1 levels in the PBSC products of relapsed and not-relapsed pts was statistically different. Than we used the log-rank test to compare RFS and median WT1 value in the PBSC products. Results at last follow-up 4 pts relapsed and 5 were still in CR. The WT1 levels in the autologous PBSC of the 4 relapsed pts were 89.96, 193.87, 779.43 and 839.63, of the 5 CR pts were 8.40, 16.96, 36.45, 74.89 and 82.49. Overall median WT1 in the PBSC products was 82,49 copies. The median WT1 levels in the PBSC products of relapsed and not-relapsed pts were 486.65 (89.96–839.63) and 36.35 (8.40–82.49) copies, respectively; this difference was statistically significant (p<0.05). Overall, median relapse free survival (RFS) from ASCT was 534 (93-1096) days. Median RFS was 360 days for pts with a WT1 level > 82,49 copies (n=4), and has not been reached for pts with a WT1 level ' 82,49 (n=5) (p=ns). Conclusions these results suggest that RT-PCR quantification of the WT1 transcript in autologous PBSC could predict AML relapse in pts who receive ASCT in CR. Higher WT1 levels should reflect higher PBSC product contamination with leukemic blasts, indicating an increased risk of relapse after ASCT. These last pts could probably benefit of other strategies than ASCT. We conclude that, if our preliminary data will be confirmed in a larger number of pts, RT-PCR quantification of WT1 transcripts should be used for MRD detection and quantification in autologous PBSC, before proceeding to ASCT; according to our preliminary data the cut-off level could be about 80 WT1 copies to discriminate which pts should receive the ASCT and which should not. Disclosures: No relevant conflicts of interest to declare.

The Addition of Rituximab to High Dose Sequential Chemotherapy (HDS) Programs with Autologous Transplantation Significantly Improves the Outcome of Patients with Refractory or Relapsed B-Cell Non Hogkin’s Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2084-2084
Author(s):  
Sergio Cortelazzo ◽  
Andrea Rossi ◽  
Emanuela Carlotti ◽  
Piera Viero ◽  
Alessandro Rambaldi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Complete Remission ◽  
Peripheral Blood ◽  
Response Rate ◽  
Autologous Transplantation ◽  
Conditioning Regimen ◽  
Event Free Survival ◽  
Free Survival

Abstract The aim of the present study was to evaluate retrospectively the clinical outcome of 2 consecutive cohorts of relapsed/refractory NHL patients treated with HDS chemotherapy with and without Rituximab and autologous peripheral blood stem cell (PBSC) transplantation. A total of 110 relapsed or refractory NHL patients with different histology (SLL n= 4, FL n=24, Low grade-transformed n=31, DLBCL n=51) entered this analysis. From October 1992 up to November 2004, patients were treated with the original HDS program (n= 33, HDS: cyclophosphamide 7 gr/sqm, methotrexate 8 gr/sqm, etoposide 2 gr/sqm) (Gianni AM et al.: N.Engl.J.Med., 1997) or a modified version (n= 15) in which methotrexate was replaced by HD-Ara-C (2 g/sqm every 12 hours for 6 days). Because the addition of Rituximab could improve the antitumor activity and the response rate before transplantation, from June 1999, Rituximab (375 mg /sqm) was given twice after HD-CTX and twice after HD-Ara-C. Following the HDS chemotherapy program, a BEAM (carmustine BCNU, 300 mg/sqm; etoposide, 200 mg/sqm; Ara-C, 4000 mg/sqm; L-PAM 140 mg/sqm) conditioning regimen with autologous PBSC transplantation was planned. By quantitative PCR analysis of BCL2/IgH chimeric gene, a molecular evaluation of minimal residual disease was performed before transplantation and during follow up on bone marrow or peripheral blood obtained from 21 patients. At enrollment, 69 patients (63%) were high risk being primary refractory (39), early relapsed (7) after first line treatment or relapsed more than twice (23). Moreover, an IPI >1 was documented in 62 patients (56%) and a bone marrow infiltration in 42 (38%). Sixteen patients (15%) had received 2 or 3 lines of conventional chemotherapy and 29 (26%) involved field Radiotherapy. At the end of HDS chemotherapy, before the conditioning regimen, the Response Rate was 82% with 76 patients achieving complete remission (CR, 69%) and 14 patients partial remission (PR, 13%). After autologous transplantation, 76 patients remained in CR (69%), 5 in PR (5%), 25 (23%) showed no response or progressive disease. Four patients (3%) died during treatment. Ninety-four patients (85%) could complete the planned program and underwent autologous transplantation and a median number of 6.3 x 10^6 cells CD34+/Kg was transplanted. After transplantation, 24 patients relapsed, 1 patient developed secondary MDS and 1 patient died because of a secondary GI tract solid tumor. With a median follow-up of 28 months (range 3–146), the 5-year estimate overall survival (OS) and event-free survival (EFS) of the whole group of patients is 48% and 39%, respectively. However, the EFS of patients not receiving Rituximab was 27% as compared to 55% registered in the R-HDS program (p= 0.005). The Cox multivariate analysis confirmed an improved OS (p=0.0000) and EFS (0.001) for patients treated with R-HDS. The achievement of a durable molecular remission was achieved in 11 out of 21 analyzed and was strongly associated with the R-HDS program. In conclusion: the response rate of relapsed or refractory NHL after HDS chemotherapy is high and more than 70% of patients can undergo conditioning regimen and autologous transplantation being in complete remission. The addition of Rituximab to HDS chemotherapy allows the collection of tumor free PBSC in most patients and significantly correlates with an improved Event Free Survival and Overall Survival.

scholarly journals Nonmyeloablative Alternative Donor Transplantation for Hodgkin and Non-Hodgkin Lymphoma: From the LWP-EBMT, Eurocord, and CIBMTR

2020 ◽  
Vol 38 (14) ◽  
pp. 1518-1526 ◽  
Author(s):  
Giancarlo Fatobene ◽  
Vanderson Rocha ◽  
Andrew St. Martin ◽  
Mehdi Hamadani ◽  
Stephen Robinson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Hodgkin Lymphoma ◽  
Peripheral Blood ◽  
Marrow Transplantation ◽  
Conditioning Regimen ◽  
Progression Free Survival ◽  
Free Survival ◽  
Blood Transplantation ◽  
Haploidentical Transplantation ◽  
Non Hodgkin Lymphoma

PURPOSE To compare the outcomes of patients with Hodgkin or non-Hodgkin lymphoma undergoing nonmyeloablative haploidentical or unrelated cord blood (UCB) hematopoietic cell transplantation. PATIENTS AND METHODS We retrospectively studied 740 patients with Hodgkin lymphoma (n = 283, 38%) and non-Hodgkin lymphoma (n = 457, 62%) age 18-75 years who received transplantations from 2009 to 2016. Data were reported to the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation, Eurocord, or Center for International Blood and Marrow Transplant Research. Of the 526 patients who received haploidentical transplantation, 68% received bone marrow and 32% received peripheral blood. All patients received a uniform transplantation conditioning regimen (2 Gy of total-body irradiation, cyclophosphamide, and fludarabine) and graft-versus-host disease prophylaxis (calcineurin inhibitor and mycophenolate). In addition, patients who received a haploidentical transplantation received posttransplantation cyclophosphamide. RESULTS Compared with haploidentical bone marrow and peripheral-blood transplantations and adjusted for age, lymphoma subtype, and disease status, survival was lower after UCB transplantation (hazard ratio [HR], 1.55; P = .001; and HR, 1.59; P = .005, respectively). Similarly, progression-free survival was lower after UCB transplantations compared with haploidentical bone marrow and peripheral-blood transplantations (HR, 1.44; P = .002; and HR, 1.86; P < .0001), respectively. The 4-year overall and progression-free survival rates after UCB transplantation were 49% and 36%, respectively, compared with 58% and 46% after haploidentical bone marrow transplantation and 59% and 52% after peripheral-blood transplantation, respectively. Lower survival was attributed to higher transplantation-related mortality after UCB transplantation compared with haploidentical bone marrow and peripheral-blood transplantation (HR, 1.91; P = .0001; and HR, 2.27; P = .0002, respectively). CONCLUSION When considering HLA-mismatched transplantation for Hodgkin or non-Hodgkin lymphoma, the data support haploidentical related donor transplantation over UCB transplantation.

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 Treatment of Familial Hemophagocytic Lymphohistiocytosis With Bone Marrow Transplantation From HLA Genetically Nonidentical Donors

Blood ◽  
1997 ◽  
Vol 90 (12) ◽  
pp. 4743-4748 ◽  
Author(s):  
Nada Jabado ◽  
Elizabeth R. de Graeff-Meeder ◽  
Marina Cavazzana-Calvo ◽  
Elie Haddad ◽  
Françoise Le Deist ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
T Cell ◽  
Graft Rejection ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Marrow Transplantation ◽  
Conditioning Regimen ◽  
Free Survival ◽  
Familial Hemophagocytic Lymphohistiocytosis ◽  
Disease Free

Abstract Familial hemophagocytic lymphohistiocytosis (FHL) is a rare genetic disorder associated with the onset early in life of overwhelming activation of T lymphocytes and macrophages invariably leading to death. Allogeneic bone marrow transplantation (BMT) from an HLA-identical related donor is the treatment of choice in patients with this disease. However, fewer than 20% of patients have a disease-free HLA-identical sibling. BMT from HLA-nonidentical related donors has previously met with poor results, with graft rejection a major obstacle in all cases. We describe BMTs from HLA-nonidentical related donors (n = 13) and from a matched unrelated donor (n = 1) performed in two centers in 14 consecutive cases of FHL. Remission of disease was achieved before BMT in 10 patients. Marrow was T-cell–depleted to minimize graft-versus-host disease (GVHD). Antiadhesion antibodies specific for the α chain of the leukocyte function–associated antigen-1 (LFA-1, CD11a) and the CD2 molecules were infused pre-BMT and post-BMT to help prevent graft rejection, in addition to a conditioning regimen of busulfan (BU), cyclophosphamide (CP), and etoposide (VP16) or antithymocyte globulin (ATG). Sustained engraftment was obtained in 11 of 17 transplants (3 patients had 2 transplants) and disease-free survival in 9 patients with a follow-up period of 8 to 69 months (mean, 33). Acute GVHD greater than stage I was not observed, and 1 patient had mild cutaneous chronic GVHD that resolved. Toxicity due to the BMT procedure was low. Results obtained using this protocol are promising in terms of engraftment and event-free survival within the limitations of the small sample. We conclude that an immunologic approach in terms of drugs used to obtain disease remission and a conditioning regimen that includes antiadhesion molecules in T-cell–depleted BMT from HLA genetically nonidentical donors is an alternative treatment that warrants further study in FHL patients who lack a suitable HLA genetically identical donor.

Results of the MRC pilot study show autografting for younger patients with chronic lymphocytic leukemia is safe and achieves a high percentage of molecular responses

Blood ◽  
2005 ◽  
Vol 105 (1) ◽  
pp. 397-404 ◽  
Author(s):  
Donald W. Milligan ◽  
Savio Fernandes ◽  
Ranjit Dasgupta ◽  
Faith E. Davies ◽  
Estella Matutes ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Complete Remission ◽  
Autologous Transplantation ◽  
Disease Free Survival ◽  
Lymphocytic Leukemia ◽  
Chain Gene ◽  
Free Survival ◽  
Number Of Patients ◽  
Disease Free

Abstract We have assessed autologous stem cell transplantation after treatment with fludarabine in previously untreated patients with chronic lymphocytic leukemia (CLL). This study is the first to enroll previously untreated patients and follow them prospectively. The initial response rate to fludarabine was 82% (94 of 115 patients). Stem cell mobilization was attempted in 88 patients and was successful in 59 (67%). Overall 65 of 115 patients (56%) entered into the study proceeded to autologous transplantation. The early transplant-related mortality rate was 1.5% (1 of 65 patients). The number of patients in complete remission after transplantation increased from 37% (24 of 65) to 74% (48 of 65), and 26 of 41 patients (63%) who were not in complete remission at the time of their transplantation achieved a complete remission after transplantation. The 5-year overall and disease-free survival rates from transplantation were 77.5% (CI, 57.2%-97.8%) and 51.5% (CI, 33.2%-69.8%), respectively. None of the variables examined at study entry were found to be predictors of either overall or disease-free survival. Sixteen of 20 evaluable patients achieved a molecular remission on a polymerase chain reaction (PCR) for immunoglobulin heavy-chain gene rearrangements in the first 6 months following transplantation. Detectable molecular disease by PCR was highly predictive of disease recurrence. It is of concern that 5 of 65 (8%) patients developed posttransplant acute myeloid leukemia/myelodysplastic syndrome. (Blood. 2005;105:397-404)

scholarly journals QBC® for the diagnosis of human and canine american visceral leishmaniasis: preliminary data

2001 ◽  
Vol 34 (6) ◽  
pp. 577-581 ◽  
Author(s):  
Daniel B. Liarte ◽  
Ivete L. Mendonça ◽  
Francisco C.O. Luz ◽  
Elza A.S. de Abreu ◽  
Gustavo W.S. Mello ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Visceral Leishmaniasis ◽  
Preliminary Data ◽  
Peripheral Blood ◽  
Buffy Coat ◽  
Promising Method ◽  
Blood Parasites ◽  
Leishmania Chagasi ◽  
Asymptomatic Carriers ◽  
Fluorescent Method

"Quantitative Buffy Coat" (QBC®) is a direct and fast fluorescent method used for the identification of blood parasites. Since Leishmania chagasi circulates in blood, we decided to test it in American visceral leishmaniasis (AVL). Bone marrow (BM) and peripheral blood (PB) of 49 persons and PB of 31 dogs were analyzed. QBC® was positive in BM of 11/11 patients with AVL and in 1/6 patients with other diseases. Amastigotes were identified in PB of 18/22 patients with AVL and in none without AVL. The test was positive in 30 out of the 31 seropositive dogs and in 28/28 dogs with Leishmania identified in other tissues. QBC® is a promising method for diagnosis of human AVL, and possibly for the exam of PB of patients with AVL/AIDS, for the control of the cure and for the identification of asymptomatic carriers. Because it is fast and easy to collect and execute, QBC® should be evaluated for programs of reservoir control.

Childhood acute myeloid leukemia: outcome in a single center using chemotherapy and consolidation with busulfan/cyclophosphamide for bone marrow transplantation.

1994 ◽  
Vol 12 (10) ◽  
pp. 2138-2145 ◽  
Author(s):  
P J Shaw ◽  
M E Bergin ◽  
M A Burgess ◽  
L Dalla Pozza ◽  
S J Kellie ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Bone Marrow Transplantation ◽  
Survival Rate ◽  
Complete Remission ◽  
Relapse Rate ◽  
Marrow Transplantation ◽  
Myeloid Leukemia ◽  
Free Survival ◽  
Acute Myeloid

PURPOSE To report the impact of bone marrow transplantation (BMT) with busulfan/cyclophosphamide (BuCy) as end consolidation in a cohort of consecutively diagnosed children with acute myeloid leukemia (AML). PATIENTS AND METHODS Between May 1987 and November 1992, 43 patients were diagnosed with AML. Tissue typing at diagnosis determined whether patients would proceed to autologous or allogeneic BMT as end consolidation after six cycles of chemotherapy. Conditioning for BMT was with BuCy, followed by allogeneic or unpurged autologous marrow infusion. RESULTS Of 37 patients who received chemotherapy, 35 achieved remission (95%) after one to six courses of treatment and 34 (92%) were transplanted. Five relapsed before BMT, four were subsequently transplanted in second complete remission (CR2) (n = 3) or untreated first relapse (n = 1), and one failed to respond to further therapy. All other patients proceeded to BMT in first complete remission (CR1). Eleven patients received allografts: one relapsed and one died of graft-versus-host disease (GvHD), for a leukemia-free survival rate of 90% at a median of 41 months after BMT (range, 3 to 60). For 23 autografts, there were two toxic deaths and eight relapses, with a leukemia-free survival rate of 61% at a median of 11 months after BMT (range, 0 to 66). The high relapse rate following autologous BMT led us to escalate the dose of Bu from 16 mg/kg to 600 mg/m2 using a single daily dose of Bu. CONCLUSION With modern supportive therapy, most newly diagnosed children with AML will enter remission and are eligible for intensification therapy. BuCy is well tolerated in children, which allowed us to escalate the dose of Bu in recent patients. Further follow-up is needed to determine whether this has an impact on the relapse rate following autologous BMT.

Busulfan/etoposide--initial experience with a new preparatory regimen for autologous bone marrow transplantation in patients with acute nonlymphoblastic leukemia

Blood ◽  
1993 ◽  
Vol 81 (2) ◽  
pp. 319-323 ◽  
Author(s):  
NJ Chao ◽  
AS Stein ◽  
GD Long ◽  
RS Negrin ◽  
MD Amylon ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Complete Remission ◽  
Median Time ◽  
Relapse Rate ◽  
Disease Free Survival ◽  
Autologous Bone Marrow ◽  
Free Survival ◽  
Acute Nonlymphoblastic Leukemia ◽  
Disease Free

Abstract Current intensive chemotherapy for acute nonlymphoblastic leukemia (ANLL) results in a complete remission in the majority of patients. Unfortunately, the duration of remission is short and most of the patients will experience a relapse of their underlying disease. Autologous bone marrow (BM) transplantation is being explored as a treatment modality designed to improve relapse-free survival. We have conducted a phase II trial exploring the combination of busulfan (16 mg/kg) and etoposide (60 mg/kg) in an attempt to improve antitumor efficacy using this novel preparative regimen. To date, 50 patients (48 with ANLL and 2 patients with biphenotypic acute leukemia) have been treated. The first 20 patients received unmanipulated BM; 28 patients subsequently received 4-hydroperoxycyclophosphamide (4–HC) (60 micrograms/mL)-purged bone marrow, and 2 patients with biphenotypic acute leukemia received both 4–HC (60 micrograms/mL) and etoposide (5 micrograms/mL)-purged BM. Thirty-four patients were in first complete remission (CR1), 12 patients in second complete remission (CR2), and 4 patients in relapse. The median time from first complete remission to BM harvest was 3 months (range, 0.8 to 4) compared with median time of 2 months (range, 1.5 to 5.0) for patients in second complete remission. The median time from harvest to transplant was 1 month for both groups (range, 0.4 to 36). A median of 0.7 x 10(8) (range, 0.2 to 1.4) mononuclear cells were infused. Patients achieved an absolute neutrophil count of > or = 500/microL at a median of 26 days (range, 13 to 96), an untransfused platelet count > or = 20,000/microL at a median of 56 days (range, 15 to 278) and a sustained hematocrit > or = 30% at a median of 50 days (range, 19 to 116). Twenty-six patients are alive and in continued CR. Follow-up of the surviving patients ranged from 6 months to 66 months with a median follow-up of 31 months. Patients receiving purged BM have an actuarial disease-free survival of 57% with a relapse rate of 28% compared with patients receiving unpurged BM whose actuarial disease-free survival is 32% with a relapse rate of 62% (P = .06 for relapse rate). The most significant extramedullary toxicities for this regimen are hepatic and cutaneous (including mucositis). The BU/VP-16 regimen is associated with a significant proportion of patients surviving disease free, especially in the group receiving purged BM. Whether this regimen offers a substantial improvement in disease-free survival over currently used regimens will require a prospective randomized study.

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.

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