Post-Transplant Therapy Is More Important Than Induction Regimen Choice in Autologous Hematopoietic Cell Transplantation (AHCT) Recipients for Multiple Myeloma (MM)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 396-396 ◽  
Author(s):  
Robert Frank Cornell ◽  
Luciano J Costa ◽  
Adetola A. Kassim ◽  
Racquel Inns-Shelton ◽  
Amrita Krishnan ◽  
...  
Keyword(s):  
High Risk ◽  
Hematopoietic Cell Transplantation ◽  
Chromosomal Abnormalities ◽  
Conditioning Regimen ◽  
Patient Characteristics ◽  
Chromosome 1 ◽  
Disease Stage ◽  
Similar Response ◽  
Induction Regimen

Abstract Background: Modern therapies incorporating bortezomib (V), lenalidomide (R), cyclophosphamide (C) and dexamethasone (D) constitute the most common doublet (RD, VD) or triplet (VRD, CVD) initial induction regimens for transplant eligible MM in the US. These regimens produce an overall response rate of >80% but their impact on longer term post-AHCT outcomes are largely unknown. Patient and Methods: We evaluated the relative impact of pre- and post-AHCT treatment on 693 patients receiving upfront AHCT after induction with RD (178), VD (161), CVD (84) or VRD (270) using data prospectively reported to the CIBMTR from 2008-2013. Analysis was limited to those receiving one line of induction chemotherapy and a single transplant with 200 mg/m2 melphalan as conditioning regimen no later than 12 months from treatment initiation. Survival endpoints were evaluated from time of AHCT and the planned use of post-AHCT maintenance incorporating R or V was also considered. Results: The table shows patient characteristics. Median number of induction cycles were 4 (range, 2 to 16) and median time to transplant was 6.5 months. Median follow up was 36 months (3 to 82) from time of transplant. Age, disease stage, disease status at transplant and cytogenetic risk were similar between the 4 cohorts. Fourteen percent had high-risk chromosomal abnormalities [17pdel, t(4;14), t(14;16), chromosome 1 abnormalities and hypodiploidy]. CVD and VD were used more frequently in patients with renal failure. Doublet use was more common before 2010 (55%) and triplets after 2010 (85%). Use of R or V post-AHCT chemotherapy was higher in with VRD (79%) and CVD (81%) cohorts vs. RD (53%) and VD (67%). No differences in pre- or post-AHCT responses were seen with regard to choice of induction agents. Pre-AHCT responses ≥VGPR were 57% for VRD vs. 45/42/51% for CVD/RD/VD respectively. Corresponding post AHCT responses at day 100 were 65% for VRD and 58/63/65% respectively. In multivariate analysis of relapse, progression free (PFS) and overall survival (OS), there was no overall difference in these outcomes based on induction regimen. High risk cytogenetics (HR = 0.57, p=0.0004 for non-high risk) and absence of planned maintenance (HR=1.55, p=0.0008) were associated with higher risk of relapse. VRD was associated with a marginal benefit in relapse risk vs. CVD (HR=0.68, p=0.04). Non-relapse mortality was similar across cohorts. Those not receiving planned post-AHCT maintenance (HR 1.69, p<0.001) and high-risk MM had higher risk of progression/death (HR in non-high risk 0.58, p<0.001); OS was lower in those with low stage (DSS or ISS I/II) vs. stage III (HR 0.6, p=0.006) and with non-high risk cytogenetics (HR 0.5, p=0.001). Patients receiving planned post-AHCT therapy had significantly improved 3-year PFS vs. no post-AHCT therapy (55% vs. 39%, log-rank p=0.0001) (figure). Conclusions: Modern induction doublets and triplets induce similar response rates and post AHCT outcomes at a median follow-up of 36 mo. Although there is an increase in use of triplets after 2010 in transplant eligible patients, our analysis suggests that the choice of induction regimen is less important than the decision to use vs. not use planned post-AHCT maintenance therapy. Figure 1. Patient characteristics. Figure 1. Patient characteristics. Figure 2. PFS by planned post-AHCT therapy vs. not: Figure 2. PFS by planned post-AHCT therapy vs. not: Disclosures Krishnan: Janssen: Consultancy; BMS: Consultancy; Jazz: Consultancy; Millenium: Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Onyx: Speakers Bureau. Gasparetto:Millennium: Honoraria, Other: Export Board Committee, Speakers Bureau; Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Hari:Celgene: Consultancy; Takeda: Consultancy; BMS: Consultancy; Janssen: Consultancy; Novartis: Consultancy; Spectrum: Consultancy; Sanofi: Consultancy.

Long-Term Outcomes of Myeloablative Conditioning and Matched-Related Donor Hematopoietic Cell Transplantation for Patients with High-Risk and Advanced-Stage Hematolymphoid Malignancies

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4383-4383
Author(s):  
Jonathan E. Benjamin ◽  
Ginna G. Laport ◽  
Laura J. Johnston ◽  
Sally Arai ◽  
Wen-Kai Weng ◽  
...  
Keyword(s):  
High Risk ◽  
Graft Versus Host Disease ◽  
Hematopoietic Cell Transplantation ◽  
Conditioning Regimen ◽  
Free Survival ◽  
Host Disease ◽  
Graft Versus Host ◽  
Related Donor

Abstract Patients with high-risk hematolymphoid malignancies who relapse or who do not achieve a complete remission to induction chemotherapy generally do not achieve long-term survival when treated with the best available non-transplant therapies. The benefit of allogeneic hematopoietic cell transplantation has been well described for patients in first complete remission, but less so for patients with advanced disease. We report the long-term follow-up of 131 patients with leukemia or lymphoma who received an HLA-matched related donor transplant following myeloablative conditioning with fractionated total body irradiation (1320cGy), etoposide (60mg/kg), and cyclophosphamide (60mg/kg). Eligibility for transplantation under this protocol included induction failure or high-risk disease that was beyond first remission. All patients were treated at a single institution. Diagnosis at the time of transplantation included ALL (n=57), AML (n=38), NHL (n=20), CML (n=10), MDS (4), JMML (n=2). Of the 95 patients with acute leukemia, 62 (65%) were not in remission at the commencement of the conditioning regimen. The median age at transplantation was 29 years (range 2–55). Seventy-four (56%) patients received unmanipulated bone marrow and the remainder received filgrastim-mobilized peripheral blood. Median follow-up of surviving patients was 8 years (range 0.3–17). The estimated five-year overall survival and event-free survival were 34% (95% confidence interval: 22–42%) and 32% (95% confidence interval: 24–39%), respectively. Leading causes of death included relapse (n=43), infection (n=11), acute graft-versus-host disease (n=8), respiratory failure (n=5) and hepatic veno-occlusive disease (n=4). Grade II–IV acute graft-versus-host disease occurred in 26% of patients. The cumulative incidence of extensive chronic graft-versus-host disease among those patients who survived beyond day 100 was 32%. These results indicate that patients with high-risk or advanced disease can experience long-term disease-free survival following an aggressive conditioning regimen that combines radiotherapy, etoposide, and cyclophosphamide. Relapse remains the most significant cause of mortality, and future efforts should focus on augmenting the graft-versus-malignancy effect.

FLAMSA Conditioning Regimen for Allogeneic Hematopoietic Cell Transplantation in High Risk Myeloid Malignancies Is Also Feasible with Partially Mismatched Donors.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3068-3068
Author(s):  
Michael Stadler ◽  
Elke Dammann ◽  
Stefanie Buchholz ◽  
Bernd Hertenstein ◽  
Juergen Krauter ◽  
...  
Keyword(s):  
High Risk ◽  
Complete Remission ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Conditioning Regimen ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Myeloid Malignancies

Abstract BACKGROUND: A conditioning regimen for HLA-identical allogeneic hematopoietic cell transplantation in relapsed, refractory, or otherwise high risk myeloid malignancies has been developed, called FLAMSA (Schmid et al.; J Clin Oncol2005; 23: 5675–5687). This protocol combines a four-day salvage chemotherapy consisting of daily fludarabine 30 mg/m2, amsacrine 100 mg/m2, and cytarabine 2000 mg/m2, followed by three days of pause, with a reduced-intensity conditioning in the subsequent week, comprising total body irradiation 4 Gy (or busulfan 8 mg/kg), cyclophosphamide 80 or 120 mg/kg and antithymocyte globulin 30 or 60 mg/kg (for related / unrelated donors, respectively). Tapering of immunosuppression until day 90 and prophylactic donor lymphocyte infusions for patients without GvHD are integral parts of FLAMSA. This protocol has since enjoyed widespread use due to its tolerability even in patients of older age or reduced performance, as well as its salvage effect and curative potential even in patients without remission before transplantation. However, the lack of a fully HLA-matched donor might render this last chance unsuitable. Our purpose was to compare outcome after FLAMSA with HLA-identical versus partially HLA-mismatched donors. PATIENTS AND METHODS: We have employed the FLAMSA protocol in 90 patients between March 2004 and June 2007, of whom 69 (the ident group) had a fully HLA-matched related (8/8 loci) or unrelated (10/10 loci) donor and 21 (the nonident group) a partially HLA-mismatched donor (1 locus in sixteen patients, 2 loci in four and haplo-identical in one). Half were females and half males, with a median age of 54 years (range: 19 to 71 years). 39 had been diagnosed with de novo acute myeloid leukemia (AML), 39 with secondary AML, 11 with myelodysplasia and one with acute lymphoblastic leukemia. 12 were in first and 4 in subsequent complete remission, whereas 74 were untreated, refractory or in relapse. Both the ident and the nonident groups were comparable regarding gender, age, diagnoses, cytogenetic risk group, remission status at transplant, as well as cytomegalovirus and sex match with their respective donor. RESULTS: With 9.2 months (range: 0.3 to 38.2 months) median follow-up of all patients, 11/21 (52%) nonident patients are alive and 10/21 (48%) in complete remission, as compared to 39/69 (57%) ident patients (not significant). Probabilities of overall and disease-free survival at 2.5 years after allogeneic hematopoietic cell transplantation (Figure) are 43% and 35% for nonident and 45% and 41% for ident patients, respectively (p = 0.54 and p = 0.56; not significant). Treatment related mortality among nonident patients was 6/21 (29%) versus 12/69 (17%) in ident patients, whereas relapse related death occurred in 18/69 (26%) in the ident group with compared to 4/21 (19%) in the nonident group. CONCLUSION: In our single-center, retrospective comparison with limited median follow-up, both fully HLA-identical and partially HLA-mismatched donors were suitable for the FLAMSA protocol. Confirmation of this finding in a prospective study is warranted. Figure Figure

Jumping Translocations of the Long Arms of Chromosome 1 (1qJT) in Myeloproliferative Neoplasms (MPNs) and Myelodysplastic Syndromes (MDS) Are Associated with High Risk of Transformation to Acute Myelogenous Leukemia (AML).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1567-1567
Author(s):  
Vesna Najfeld ◽  
Joseph Tripodi ◽  
Steven Fruchtman ◽  
Lewis R. Silverman ◽  
Richard T. Silver ◽  
...  
Keyword(s):  
High Risk ◽  
Copy Number ◽  
Conflicts Of Interest ◽  
Myeloproliferative Neoplasms ◽  
Chromosomal Rearrangements ◽  
Patient Characteristics ◽  
Myelogenous Leukemia ◽  
Chromosome 1 ◽  
Genetic Event

Abstract Abstract 1567 Poster Board I-591 Jumping translocations (JT) are rare cytogenetic events where by a part of one chromosome is translocated to several recipient chromosomes creating multiple related clones within a single patient (pt). Over two-thirds of the already ∼70 reported cases with JTs had multiple myeloma (JR Sawyer et al, 2005). The most frequent donor chromosome involved in JT is the long arm of chromosome 1 (+1q). Although abnormalities of 1q are the 4th most common recurrent rearrangements in both MPN and MDS, 1qJT have been rarely reported in these disorders. Their role in the pathogenesis of MPN and MDS remains unknown. We report a study of 23 pts with myeloid malignancies to determine the role of 1qJT in MPN and MDS. Patient characteristics are shown in Table 1. Of 512 MPN pts (PV=361, PMF=151) cytogenetically evaluated at our institution, we identified 3 pts (PV=2, PMF=1) at diagnosis with 1qJT (0.6% incidence). Additionally 4 of 169 (PV=96, PMF=69) pts with MPN acquired 1qJT during the serial follow up studies over a period of 11 years (the overall incidence was 1.3%, and 4.2% in pts with cytogenetically abnormal karyotypes). Table 1 Characteristics of 23 pts with 1qJT at baseline and sequential studies *One patient had stem cell transplantation The median follow up time was 78 months (mos) and the average time to acquire 1qJT was 58 mos. usually only one or two cells with +1q were initially identified but over time the number of partner chromosomes increased. In 4 pts who acquired 1qJT, this genetic event occurred an average after 5 years while in 1 pt it occurred after 11 years. However, once 1qJT was acquired, 3 of 4 pts developed AML, within an average time of 8 months. The transformation to AML was associated with an increased 1q translocated copy number, suggesting that 1qJT may be a marker of disease progression. By contrast, the incidence of 1qJT at diagnosis of MDS was 0.04% (4 of 1,000). Each of 4 pts, who presented with 1qJTs, had up to three different related clonal populations, all characterized by +1q translocated to 3 different chromosomes. The presence of 1qJT at diagnosis was associated with transformation to AML (3 of 4 pts) after less than 4 mos. Additionally of the 300 pts who were sequentially studied for over a period of 34 mos, 12 pts acquired 1qJT within 27 months (the overall incidence 4%, or 8% among the cytogenetically abnormal). Once 1qJT was acquired, transformation to AML occurred after 8 months (range 0-32) in 10 of 12 pts (83%). This was accompanied with an increased number of JT partner chromosomes. Overall, trisomy 1q, was “jumping” to as many as 11 different chromosomes, creating 11 related clonal populations. All chromosomes except 2, 10 and 12, were recipients of 1qJT, with a greater frequency affecting acrocentric chromosomes (55%). More importantly, 81% of the breakpoints in recipient chromosomes were in the pericentromeric regions. This study represents the largest series of pts with MPN and MDS characterized by 1qJT. The presence of 1qJT at diagnosis or the subsequent acquisition of 1qJT was associated with transformation to AML in 86% of MPN cases and 83% of MDS cases after an average of 8 months. The prognosis of pts with 1qJT tends to be dependent on the translocated 1q copy number: the higher the number of “jumping” 1q being translocated to different partner chromosomes the shorter the time to transformation to AML. These data strongly indicate that 1qJT in MPN and MDS patients represents clonal chromosomal rearrangements associated with a high risk of imminent transformation to AML. Disclosures No relevant conflicts of interest to declare.

scholarly journals Allogeneic Hematopoietic Cell Transplantation with Myeloablative Conditioning Regimen of Reduced Toxicity Is Associated with Favorable Survival in Patients with Secondary Acute Myeloid Leukemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 21-22
Author(s):  
Eleni Gavriilaki ◽  
Chrysavgi Lalayanni ◽  
Ioanna Sakellari ◽  
Christos Varelas ◽  
Despina Mallouri ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Conditioning Regimen ◽  
Transplant Recipients ◽  
Myeloablative Conditioning ◽  
Comorbidity Index ◽  
Reduced Toxicity ◽  
Reduced Intensity

Background: Secondary or treatment-related acute myeloid leukemia (sAML) is associated with poor outcomes. Although allogeneic hematopoietic cell transplantation (alloHCT) is the treatment of choice, patient eligibility criteria and optimal conditioning regimen remain under study. We have previously shown an advantage of a myeloablative conditioning regimen with reduced toxicity (Fludarabine 150mg/m2, Treosulfan 42g/m2, FluTreo) compared to a reduced intensity regimen. However, the long-term effects of this regimen remain unknown, especially in comparison to patients not receiving alloHCT. Aims: We hypothesized that patients transplanted with FluTreo would have a long-term survival advantage over other treatment alternatives. Methods: We retrospectively studied consecutive patients treated for sAML in our center over the last two decades (1998-2018). Exclusion criteria were: age&gt;70 years, ECOG performance status≥3 at presentation, induction regimens≤2, and autologous or haploidentical HCT because these were performed in individual patients. Since 2013, we have introduced FluTreo for patients with a suitable donor that would have been previously eligible only for reduced intensity conditioning/RIC. The following factors were studied in the whole cohort: age, type of disease (treatment-related or post myelodysplastic syndrome/MDS), previous intensive chemotherapy cycles, cytogenetic risk, overall (OS) and disease-free survival (DFS). In transplant recipients, we also recorded HCT-comorbidity index/CI score, cumulative incidence (CI) of graft-versus-host disease (GVHD), and treatment-related mortality (TRM). Follow-up was calculated from diagnosis in the whole cohort; and from date of transplant in the sub-group analysis of transplant recipients. Results: We studied 19 FluTreo recipients compared to 46 recipients of other conditioning regimens (38 myeloablative and 8 RIC), and 52 patients treated only with chemotherapy. Complete remission (CR) had been achieved in all FluTreo recipients before HCT, compared to 53% of other transplants, and 44% of chemotherapy only patients (p&lt;0.001). As expected, median age was increased in FluTreo and chemotherapy only patients (59 and 58 years respectively), compared to other transplants (48 years, p&lt;0.001). There was no other difference in baseline characteristics. With a median follow-up of 43 (range 13-204) months in surviving patients, 4-year OS was 40.3% in FluTreo versus 31.3% in other transplants and 11.8% in chemotherapy only patients (p&lt;0.001, Figure 1A). In the multivariate analysis, achieving CR (p&lt;0.001) and the FluTreo group (p&lt;0.001) were associated with favorable OS, independently of age and cytogenetic risk. 4-year DFS was 32.3% in FluTreo, versus 29.3% in other transplants and 10.2% in chemotherapy only patients (p=0.001, Figure 1B). Within transplanted patients, there was no significant difference in GVHD, relapse and TRM between FluTreo and other transplants. Within the FluTreo group, acceptable rates of CI in severe acute and extensive chronic GVHD were observed (15.2% and 18.4%, respectively). Similarly, 4-year CI of TRM reached 30.4%, despite a median HCT-CI of 3 (0-7), age of 59 (51-67) years, 4 lines of treatment (3-6), and a majority of matched unrelated donors (13/19). Conclusion: Our real-world study confirms that alloHCT with FluTreo expands the transplant population with similar safety and efficacy to previous transplant modalities in sAML patients. Achievement of CR remains a major predictor of OS in these patients. The choice of alloHCT in this unique patient population of a rather older age and comorbidity index needs to be revisited. Figure 1 Disclosures Gavriilaki: Omeros Pharmaceuticals: Consultancy.

Voriconazole in Primary Prophylaxis Reduces the Incidence of IFI in High Risk Hematologic Patients.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5349-5349 ◽  
Author(s):  
R. Rojas ◽  
J. Serrano ◽  
C. Martin ◽  
S. Tabares ◽  
M. Capote ◽  
...  
Keyword(s):  
High Risk ◽  
Bacterial Infections ◽  
Hematopoietic Cell Transplantation ◽  
Fungal Infections ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Primary Prophylaxis ◽  
Antifungal Treatment ◽  
Severe Neutropenia ◽  
Severe Mucositis

Abstract OBJETIVE: To analyse the eficacy and safety of voriconazole as primary prophylaxis in hematologic patients with high risk of invasive fungal infections (IFI) due to severe neutropenia after induction/intensification chemotherapy for acute myeloid leukemia (AML) and allogeneic hematopoietic cell transplantation (allo-HCT). PATIENTS AND METHODS: between June-04 and May-05 we prospectively included 31 episodes of severe neutropenia (&lt;0,5x109/l, &gt;10 days) after chemotherapy for AML and 24 patients submitted to an allo-HCT in a primary prophylaxis treatment with voriconazole (200 mg po/12 h) from the starting of chemotherapy until the neutrophils recovery (&gt;0,5x109/l) in AML and from the starting of the conditioning regimen until the withdrawal of immunossupression in allo-HCT (by three months after transplantation) and we compared both groups with historic controls (63 episodes of neutropenia after AML and 31 allo-HCT) treated between January-03 and May-04 with fluconazole as primary prophylaxis (400 mg po/24 h) in the same way. Drugs were adjusted to weight in children. In case of severe mucositis voriconazole or fluconazole were temporarily used intravenously. EORTC/MSG criteria for IFI definitions were used and galactomanane antigen determinations were done twice a week. In case of neutropenic fever, empiric antifungal treatment was started in the fith day with lyposomal amfotericin B the primary prophylaxis was stopped. RESULTS: AML GROUP: We didn’t find statistical differences among groups of VORI (n=31) and FLUCO (n=63) when we analyse age (VORI mean 49y, 18–64;FLUCO mean53y,21–72), sex, FAB classification, disease status, number of broad spectrum antibiotics, bacterial infections, days of neutropenia (19 vs 18) and days of fever (5.8 vs 7.2). The number of detected IFI was superior in the fluconazole group in spite of no statistical differences (VORI 3 vs FLUCO 11; 9,6% vs 17,4%, p=NS) with a sum of proven+probable 2 vs 5 (6,4% vs 8%, p=NS). Interestingly, the number of fatal IFI was statistical superior in the fluconazole group (VORI 0 vs FLUCO 4, p&lt;0,05) and the need for empiric antifungal treatment was superior in the fluconazole group (VORI 19,3% vs FLUCO 50,8%, p=0,004). None patient had to interrupt voriconazole due to toxicity. ALLO-HCT GROUP: we didn’t find statistical differences among groups of VORI (n=24) and FLUCO (n=31) when we analyse age (VORI mean 37y, 2–64 and FLUCO mean 30y, 5–56), sex, diagnosis and status at transplantation. In spite of differences in the conditioning regimen with more reduced-intensity conditioning regimen in the voriconazole group, both groups were similar when we analyse incidence of aGVHD II–IV grades, steroids use, VOD, number of bacterial infections, CMV infections and cGVHD. The days of fever were superior in the fluconazole group (VORI 4 vs FLUCO 7, p=0,04) and so the need for empiric antifungal treatment (VORI 6 vs FLUCO 16, p=0,042). The number of IFI was superior in the fluconazole group (VORI 2 vs FLUCO 10, p=0,04) and the number of fatal events due to IFI was superior in the fluconazole group (VORI 1 vs FLUCO 5, p&lt;0,05). Voriconazole was temporarily stopped in two patients with hepatic aGVHD and one patient with VOD. Three patients developped hepatic colestasis by day +75 wich was reversible after discontinuating voriconazole one week. CONCLUSSIONS: voriconazole as primary prophylaxis of IFI is a safety and well tolerated efective drug wich reduces the need for empiric antifungal treatment and the fatal events due to IFI in AML and allo-HCT.

Gemtuzumab Ozogamicin as Maintenance Therapy after Autologous Stem Cell Transplantation (ASCT) in Patients with Acute Myeloid Leukemia (AML).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4380-4380
Author(s):  
Nicola Cascavilla ◽  
Carlo Bodenizza ◽  
Angelo Michele Carella ◽  
Matteo Dell’Olio ◽  
Antonietta Pia Falcone ◽  
...  
Keyword(s):  
High Risk ◽  
Maintenance Therapy ◽  
Conditioning Regimen ◽  
Gemtuzumab Ozogamicin ◽  
Tolerability Profile ◽  
Platelet Recovery ◽  
Small Series ◽  
Number Of Patients ◽  
Induction Regimen

Abstract The role of ASCT in AML appears to be appropriate in patients with favorable cytogenetic features whereas allogeneic SCT is appropriate in those with high-risk cytogenetic features. Gemtuzumab ozogamicin (GO), a monoclonal antibody conjugated to the calicheamicin, targets the CD33+ cell surface marker that is expressed on cells in the majority of AML patients. Clinical trials currently underway are investigating the role of GO in consolidation therapy. We hypothesized that GO could have beneficial effects as maintenance therapy after hematopoietic SCT in high-risk patients. Here we report data on 4 AML patients in CR who received 4 doses of GO as maintenance therapy following ASCT. Our approach differs from previous reports in the literature in that, instead of using GO to induce a first remission or re-induce a second remission after relapse, we administered GO to patients while they remained in remission, two months after undergoing ASCT. Patient #1 was a 64 year-old male with 88% CD33 expression at diagnosis. This patient had previously undergone an ASCT using a conditioning regimen of Bu+Cy. He was in second CR following an induction regimen of 2 cycles of fludarabine + cytarabine + idarubicin. Patient #2 was female, aged 67 years and had 90% CD33 expression at diagnosis. She was in first CR following an induction regimen of 2 cycles of etoposide + cytarabine + idarubicin. Patient #3 was a 69-year old male with 95% CD33 expression at diagnosis. He was in first CR following an induction regimen of 2 cycles of fludarabine + cytarabine. Patient #4 was a 59 year-old male with 93% CD33 expression. He was in first CR after a second line treatment with mitoxantrone, cytarabine and etoposide. Histocompatible donors were not available for any of the patients. Three months after attaining CR, all 4 patients received a myeloablative conditioning regimen with B(A)VC, Bu+Cy, Bu+Cy and TBI+Melphalan, respectively, and underwent ASCT. Two months after the ASCT procedure, patients initiated treatment with GO: GO was administered alone for 4 doses with 28 days between doses (two patients received 6 mg/mq for the two first doses and 3 mg/mq for the two last doses; two patients received 3 mg/mq for four doses). All four patients remain alive and in CR at +17, +13, +11and + 5 months. Overall survival at the time of reporting is +35, +15, +13 and +8 months in patients 1, 2, 3 and 4, respectively. There were no cases of grade 3 or 4 liver toxicity and bleeding was not observed in any of the patients. Thrombocytopenia (50,000–100,000 cells/μL) occurred in all four patients and neutropenia (500–1000 cells/μL) in two patients. In conclusion in our small series GO demonstrated good efficacy when administered in fractionated doses as maintenance therapy after ASCT in patients with CD33+ AML in first or second CR. GO showed an acceptable tolerability profile, with no severe hepatotoxicity and no bleeding. Thrombocytopenia occurred in all three patients and in all cases there was a rapid platelet recovery. A GO dose of 3 mg/m2 appeared to be better tolerated than the higher dose (6 mg/m2) and will be used in future studies. If confirmed in a study involving a larger number of patients, our results could support a new therapeutic role for GO, namely as a maintenance therapy for patients in CR following hematopoietic SCT.

Low Relapse without Excessive Transplant-Related Mortality Following Allogeneic Stem Cell Transplantation in Patients with High Risk Secondary Acute Myeloblastic Leukaemia and Myelodysplastic Syndromes, Long-Term Outcomes in a Single Centre Experience.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4308-4308
Author(s):  
Jean El-cheikh ◽  
Luca Castagna ◽  
Sabine Furst ◽  
Catherine Faucher ◽  
Benjamin Esterni ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Allogenic Stem Cell Transplantation ◽  
Related Mortality

Abstract Abstract 4308 Allogenic stem cell transplantation (Allo-SCT) as a therapy for secondary acute myeloid leukaemia (sAML) and myelodisplastic syndromes (MDS) is the most powerful treatment option. However, (Allo-SCT) is also complicated by a high risk for treatment-related morbidity and mortality. We analysed retrospectively the data of 70 patients transplanted at our institution from June 1995 to december 2008, 44 patients (63%) with sAML and 26 patients (37%) with MDS was treated with (Allo-SCT); median age at diagnosis was 41 years, (15-70), and the median age of 42, 5 years (16-70) at transplantation; The conditioning regimen was myeloablative combining (cyclophosphamide and TBI) in 16 patients (23%) and 54 patients (77%) was with a reduced intensity conditioning (RIC) regimens combining fludarabine, busulfan, and antithymocyte globulin; 11 patients (16%) were infused with bone marrow (BM), 55 patients (79%) peripherical blood stem cells (PBSC), and 4 patients (5%) cord blood cells; in 49 cases (70%) donor was a HLA identical sibling and in 21 (30%) was a matched unrelated donor; 41 patients (59%) carried high risk cytogenetic features, like (7q-, 5q-, > 3 alterations), while was normal in 24 patients (34%), and in 5 patients (7%) was unknown. Disease status at transplantation was as follow: CR in 24 patients (34%), 34 patients (49%) was refractory or in progression after treatment, and 12 patients (17%) was with a stable disease. With a median follow-up of 55 months (3-150), 30 patients (43%) are alive, the overall survival OS at 2 years and 5 years was 48 % and 39% respectively, and after ten years of follow up, OS was 30%, 95%CI [17.8-50.8]. We observed also that 26 % of refractory patients and 54% of patients in CR are alive at five years of transplantation. The probability of progression after transplantation at five and ten years was 31% with 95%CI [20.-46.5]. 2 years and 5 years treatment related mortality (TRM) was 23% and 26% respectively, and no modification at ten year, 95%CI [14.3-37.3]. TRM occurred in 16 patients (23%). Cause of death was; infections in 5 patients (7%), GvHD in 3 patients (4%), GvHD and infection in 3 patients (4%), multi organ failure (MOF) in 5 patients (7%). In multivariate analysis; OS, PFS or TRM, were not influenced by donor type (HLA id sibling vs others), conditioning regimen (RIC vs MAC), and stem cell source (bone marrow vs PBSC). Allogenic stem cell transplantation can be considered as a good option for the treatment of patients with high risk sAML and MDS when compared with the remission rate at five years of the other nonallogeneic SCT therapies. Disclosures: No relevant conflicts of interest to declare.

Allogeneic Hematopoietic Cell Transplantation From Combined Haploidentical Family Members and Unrelated Cord Blood (CB) Can Benefit High Risk Patients Lacking HLA-Identical Donors.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3378-3378 ◽  
Author(s):  
Elizabeth Shima Rich ◽  
Andrew Artz ◽  
Theodore Karrison ◽  
Lucy A Godley ◽  
Olatoyosi Odenike ◽  
...  
Keyword(s):  
High Risk ◽  
Cord Blood ◽  
Median Time ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Bone Marrow Cells ◽  
Cord Blood Transplantation ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Blood Transplantation

Abstract Abstract 3378 Poster Board III-266 Introduction: Haploidentical-cord blood transplantation is a promising approach for patients (pts) who lack HLA donors and may improve rates of early engraftment while allowing long term cord blood reconstitution with low rates of GVHD. We enrolled 29 pts (17 AML/MDS, 4 ALL, 3 CML, 4 NHL/HL, 1 severe aplastic anemia) lacking HLA identical donors. The median age was 40 years (range, 4-67), and median weight was 75 kg (range, 14-125). Twenty-two (76%) pts had active disease at time of transplant; 6 had prior autologous transplants. 14 pts were Caucasian; 15 were other race or ethnicity. The haploidentical donor was the mother in 4; father in 3; child in 10; sibling in 10; and half-sibling in 2 cases. The median haploidentical CD34+ dose was 2.51 × 106/kg (range, 1.25-10.95); CD3+ cells were 1.0 × 104/kg (range, 0.3-3.7). Single unrelated CB units were matched by low resolution at HLA-A and B and high-resolution at DRB1, and matched 6/6 in 2 pts; 5/6 in 18 pts; 4/6 in 9 pts. Median cord total nucleated cells equaled 1.93 × 107/kg (range, 1.07-9.36); CD34+ cells were 0.08 × 106/kg (range, 0.03-0.75). The conditioning regimen for 18 pts was fludarabine (Flu) (30 mg/m2 on d-7 through -3), melphalan (Mel) (70 mg/m2 on d -3 and -2), and Thymoglobulin (rATG) (1.5 mg/kg on d-7, -5, -3, -1). Eleven pts received Flu, thiotepa (5 mg/kg on d -7 and -6), total-body irradiation (TBI) (12 Gy lateral opposed fields in 2 Gy fractions BID on d-3 through -1), and rATG. GVHD prophylaxis consisted of tacrolimus (Tac) + methylprednisolone or Tac + mycophenolate. Engraftment: Two pts died early (sepsis, CVA). Three other pts failed to engraft with either haploidentical or CB and died of infection on d36, 43, and 63. One of these had anti-donor HLA antibodies. 24 pts engrafted with a median time to ANC >500/mL of 10 days (range, 9-31) and median time to sustained platelets >20,000/mL of 20 days (range, 15-63). In the majority of pts, early haploidentical engraftment was replaced by durable engraftment of CB by 100 days. However, 3 pts had persistent hematopoiesis associated with only the haploidentical donor, while a fourth pt engrafted with only CB on day 31. Late graft failure and death from sepsis occurred in one of the patients with haploidentical engraftment. In unfractionated peripheral blood or bone marrow cells, median haploidentical chimerism was 95% (range, 0-100) on d14; 76% (range, 0-95) on d30; 6% (range, 0-87) on d100. Median unfractionated cord chimerism was <5% (range, 0-100) on d14; 20% (range, 0-100) on d30; 85% (range, 0-100) on d100. In the CD3+ compartment, median haploidentical chimerism was 95% (range, 0-100) on d14; 86% (range, 0-95) on d30; 6% (range, 0-79) on d100. Median CD3+ cord chimerism was 5% (range, 0-100) on d14; 26% (range, 0-100) on d30; 90% (range, 1-100) on d100. Toxicities and outcome: Other fatal toxicities included VOD (1), EBV-associated PTLD (1), ARDS (1), cardiac arrest (1), intractable seizures (1). Two patients developed TTP and later died of complications related to sepsis. Five pts relapsed of whom 4 have died. Acute GVHD (aGVHD) grade II occurred in 3 pts, one of whom developed the only case of chronic GVHD after failing to continue prograf. No aGVHD grade III-IV was seen. Twelve pts are currently alive; 11 are without disease. The median follow up for survivors is 186 days (range, 16-642). Estimated one year survival is 26% (95%CI, 6-46), and PFS is 19% (1-36). Conclusions: Combined haploidentical and CB transplantation results in early haploidentical engraftment followed by durable CB predominance in a majority of pts. The median times to neutrophil engraftment are considerably shorter - and the range narrower - than with other methods of cord blood transplantation. Early haploidentical engraftment failed in four patients; cord blood engraftment also failed in three of these pts and in three others. Rates of acute and particularly of chronic GVHD are low. Durable remissions can be achieved even in high risk pts regardless of age or remission status at the time of transplant. Disclosures: Rich: Genzyme: Research Funding. Odenike:Genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees. van Besien:Genzyme: Research Funding.

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