Impact of Deletion 17p On the Outcome of Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3099-3099
Author(s):  
Caitlin L. Costello ◽  
Edward D. Ball ◽  
Sue Corringham ◽  
Hongying Li ◽  
Karen Messer

Abstract Abstract 3099 Background: The development of a risk-stratification model that relies on molecular cytogenetic markers to assess disease aggressiveness and provide therapeutic guidance would be beneficial for the management of patients with multiple myeloma (MM). High-risk cytogenetic abnormalities, including deletion 17p (del17p), are known to confer a poor prognosis. Intensified consolidation with high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) following induction therapy has been proposed as the preferred initial treatment for high-risk MM, such as del17p. With this background, we report the impact of del17p on the timing and outcome of transplant in patients with MM. Methods: We performed a retrospective review of 226 patients with MM who underwent HDT/ASCT at the University of California, San Diego Moores Cancer Center between 1/2000 and 7/2011. Conventional cytogenetic analyses were utilized for all patients either at diagnosis or at relapse, but prior to ASCT. Fluorescence in situ hybridization was also assessed when available. The primary objective was to evaluate the impact of del17p, a known high-risk chromosomal abnormality, on the overall survival (OS) and progression-free survival (PFS) after ASCT, compared with patients without chromosomal abnormalities. A secondary objective was to assess the OS and PFS for patients with del17p who received ASCT within a year of diagnosis, compared with those who underwent ASCT more than 12 months from diagnosis. Results: In 226 patients with conventional cytogenetic data prior to ASCT, chromosomal abnormalities were noted in 82 (36%) patients. Of these, 21 (25%) patients harbored a del17p abnormality. Table 1 shows the patient characteristics and ASCT outcomes. Prior to undergoing ASCT, 4 (19%)patients with del17p achieved a complete remission (CR) or stringent complete remission (sCR), and 6 (29%) achieved a CR or sCR after ASCT. In patients without chromosomal abnormalities, 19 (13%) achieved CR or sCR prior to ASCT, and 45 (31%) achieved it after ASCT. Median follow-up of surviving patients was 47 months (range 5–283). Median PFS after ASCT in patients with del17p and normal cytogenetics were 8.3 months (95%CI: 4.6-N/A) and 33 months (95%CI: 21.7–61.8), respectively (HR 2.15, 95%CI: 1.19–3.89; p=0.011) (Figure 1). Median OS after ASCT in patients with del17p and normal cytogenetics were 47.5 months (95%CI: 19.9-N/A) and 68 months (95%CI 51.1-N/A), respectively (HR: 2.27, 95%CI 1.15–4.48; p=0.018) (Figure 2). Median PFS in patients with del17p who received an ASCT after 12 months and within 12 months from diagnosis was 6.13 months (95%CI: 2.7-NA) and 22.6 months (95%CI: 5.4-NA), respectively (HR=1.22, 95%CI 0.40–3.82; p=0.71). Median OS in del17p patients who received an ASCT after 12 months and within 12 months from diagnosis was 65.6 months (95%CI: 19.3-NA) and 47.5 months (95%CI: 19.9-NA), respectively (HR=0.97, 95%CI 0.26–3.62; p=0.96). Conclusions: In this single center study with long follow up, we demonstrate that a del17p abnormality in MM confers a shorter PFS and OS after ASCT. Furthermore, the use of HDT/ASCT as part of the upfront treatment plan within 12 months of diagnosis does not significantly affect the outcome in patients with a del17p abnormality. Further studies are required to better define a risk-stratified treatment plan for this subset of high-risk multiple myeloma. Disclosures: No relevant conflicts of interest to declare.

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5884-5884 ◽  
Author(s):  
Ahmad Antar ◽  
Mohamed A Kharfan-Dabaja ◽  
Hussein Abou Ghaddara ◽  
Rami Mahfouz ◽  
Ali Bazarbachi

Abstract Background: 5-Azacidine (5-AZA) is a DNA hypomethylating agent with proven clinical activity in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). A recent non-randomized study reported promising results with the use of lower doses of 5-AZA as maintenance therapy after hematopoietic stem cell transplantation (HSCT). It is important to note that 5-AZA has an immunomodulatory effect and might enhance the graft-versus-leukemia (GVL) effect. Here, we report the successful use of 5-AZA maintenance following allogeneic HSCT in patients with high risk AML and MDS. Patients and methods: Nine patients (M=6, F=3; median age=49 (36-65) years ) with high-risk AML (n=6 including 2 abnormal karyotypes) or MDS (n=3 including 1 abnormal karyotype) received 5-AZA as post-transplant maintenance at a dose of 32mg/m2 daily for 5 days every 4 weeks starting at a median time of 100 (30-210) days post-transplant. All patients were in complete remission at initiation of 5-AZA. A median of 12 cycles (1-18) were delivered. Patients’ characteristics, treatment details, response and side effects are summarized in Table I. Results: After a median follow-up of 19 months post HSCT and 15 months after starting 5-AZA treatment, five patients with normal karyotype are still in CR. Conversely, all three patients with abnormal karyotype rapidly developed disease recurrence while they were receiving 5-AZA after a median of 3 months. Overall, the actuarial 1-year progression free and overall survival rates were 65% and 90%, respectively. 5-AZA was generally well tolerated with only mild thrombocytopenia observed in 2 patients. No clinically evident graft-versus-host disease exacerbation was observed. Conclusion: These results suggest that Low-dose 5-AZA is an effective maintenance therapy post- allogeneic SCT in high-risk AML and MDS particularly when a normal diploid karyotype is present. The relative lack of efficacy in the presence of an abnormal karyotype is intriguing and questions whether these subjects might benefit from higher doses of 5-AZA or other novel therapies within the context of a well-designed clinical trial. Prospective clinical trials and longer follow-up are needed to confirm these observations. Abstract 5884 TABLE I.Patients characteristics and Outcomes After Azacitidine maintenanceSubject #123456789Age at transplant655848433649495851genderMMFMFMFMMDiseaseAMLAMLAMLAMLSecondary AMLSecondary AMLMPD/MDSMDS (RAEB-2)MDS (RAEB-2)cytogeneticnormalnormalT(6,9)normalDel 5normalnormalnormalHypoploidy(43-45)Molecular abnormalityNoneNoneNoneFLT3 ITDNoneNoneNoneNoneNoneDisease status at HSCTCR2CR3CR1CR1RefractoryCR1PRPRCR1Donor typeMRDMRDMRDMRDMUDMRDMRDMRDMRDConditioningFB2+ATGFB3+ATGFB3+ATGFB4+ATGFB3+ATG+ TBI (4Gy)FB4+ATGFB4+ATGFB3+ATGFB2+ATGGVHD prophylaxisCSACSACSACSACSACSACSACSACSA, mycophenolate mofetilTime from HSCT to 5-AZA (days)37701001503021010055104Disease status at 5-AZACRCRCRCRCRCRCRCRCRnb of cycles12131241218129ToxicityNoneNoneNoneNoneGrade II thrombocytopeniaGrade II thrombocytopeniaNoneNoneNoneGVHD after 5-AZANoNoYesYesYesNoYesNoNoDisease recurrencenonoyesnoyesnononoyesSalvage therapy if recurrenceN/AN/AChemotherapy followed by DLIN/ANoneN/AN/AN/AChemotherapy followed by DLIProgression free survival, months13+24+124+319+21+18+10Status at last follow upCRCRCRCRdiedCRCRCRCRSurvival, months13+24+18+24+519+21+18+34+ Stem cell source for all patients: peripheral blood; CR: complete remission; PR: partial remission; CSA: cyclosporine A; MRD: matched related donor; MUD: matched unrelated donor; PBSC: peripheral blood stem cell; CCR: continuous complete remission; FB4: 5 days fludarabine plus 4 days busulfan (130 mg/m2/day); FB3: 5 days fludarabine plus 3 days busulfan (130 mg/m2/day); FB2: 5 days fludarabine plus 2 days busulfan (130 mg/m2/day) ATG: anti-thymoglobuline; DLI: donor lymphocyte infusion. Disclosures Off Label Use: Azacitidine maitenance post HSCT.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8040-8040
Author(s):  
Koji Sasaki ◽  
Gary Lu ◽  
Chitra Hosing ◽  
Uday R. Popat ◽  
Sairah Ahmed ◽  
...  

8040 Background: Approximately 15-20% of patients with multiple myeloma (MM) present with t(11;14)(q13;q32) involving IgH and CCND1-XT genes. In this study, we report the impact of the t(11;14) on the outcome of patients with MM. Methods: We performed a retrospective chart review on patients with MM who underwent high-dose chemotherapy followed by auto-HCT at the M.D. Anderson Cancer Center between 2/2000 and 8/2010, and had conventional cytogenetic (CC) or fluorescent in situ hybridization (FISH) results available before transplant. The primary objective was to compare the progression free survival (PFS) and overall survival (OS) of patients with t(11;14) to patients without chromosomal abnormalities. Results: CC or FISH studies were available for 1239 patients: 863 normal, 28 with t(11;14), 348 with other abnormalities. Concurrent high-risk abnormalities on CC or FISH were seen in 15/28 patients with t(11;14): del(13q) in 11 , del(17p) in 3, and t(14;16)(q32;q23) in 1. Induction treatment in patients with t(11;14) was: bortezomib + dexamethasone +/- thalidomide/lenalidomide : 15 (53%), thalidomide or lenalidomide + dexamethasone: 11 (39%), others 2 (8%); they received auto-HCT after a median of one line (1-7) of therapy. Median follow up in surviving patients was 39 months. There was no significant difference in median time from diagnosis to auto-HCT from diagnosis (6.9 vs. 7.7 months, p=1.0), disease status at auto HCT (>PR1: 82 vs. 76%, <PR1: 7 vs. 11%, relapsed 10 vs. 13%), complete remission (CR: 21% vs. 32%; p=0.30), very good partial remission (VGPR: 29% vs. 21%; p=0.23) or overall response (75% vs. 85%; p=0.18) between patients with t(11;14) and normal karyotype. Median PFS in patients with t(11;14) and normal karyotype was 15.7 months and 35.9 months, respectively (p=0.017). Median OS in patients with t(11;14) and normal karyotype was 51.4 months and 88.4 months, respectively (p=0.03). There was no difference in PFS (p=0.25) or OS (p=0.71) in patients with t(11;14), with or without other high-risk chromosomal abnormalities. Conclusions: In this large single center study with a long follow up, we demonstrated that t(11;14) in MM is associated with a shorter PFS and OS in the context of auto-HCT.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 333-333 ◽  
Author(s):  
Sairah Ahmed ◽  
Heather Lin ◽  
Veera Baladandayuthapani ◽  
Mubeen A Khan ◽  
Gary Lu ◽  
...  

Abstract Abstract 333 Impact of Non High-Risk Chromosomal Abnormalities on the Outcome of Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma Background: Despite novel therapeutic agents and high-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HCT), most patients eventually progress and die of their disease. Recent advances in cytogenetic, molecular and genomic studies have led to identification of several chromosomal and molecular abnormalities. These abnormalities are important predictors of response to therapy, progression-free survival (PFS) and overall survival (OS). On conventional cytogenetic (CC) analyses, del 13, t(4;14), t(14;16) and del 17p are considered high-risk (HR). On Fluorescence in situ hybridization (FISH) analysis, all except del 13 are considered HR (Munshi, N et al. Blood 2011 117: 4696–4700). However there are a number of chromosomal abnormalities whose significance is not clearly identified (non-HR). In this study we report the impact of these non-HR chromosomal abnormalities on the outcome of patients who received high-dose chemotherapy and auto-HCT. Methods: We performed a retrospective review of patients with multiple myeloma who underwent high dose chemotherapy followed by auto-HCT at the M.D. Anderson Cancer Center. Between 10/1991 and 12/2010, 1570 patients received auto-HCT. The results of CC studies were available for 1329 patients, either at diagnosis or at relapse, but before auto-HCT. The primary objective was to study the impact of non-HR chromosomal abnormalities on PFS and OS, and to compare them to patients without chromosomal abnormalities. Results: Patient characteristics and major outcomes are summarized in the attached Table. In 1329 patients with available CC analyses before auto-HCT, chromosomal abnormalities were identified in 405 (30%) patients. One-hundred and seven (7%) patients had known HR chromosomal abnormalities, while 298 (23%) patients had non-HR chromosomal abnormalities. Fifty (17%) patients with non-HR chromosomal abnormalities and 296 patients (32%) with normal CC achieved complete or stringent complete responses (CR + sCR) (p=0.0001). Median follow up in surviving patients was 36 months. Median PFS in patients with non-HR chromosomal abnormalities and normal CC were 18.2 months (95%CI: 16–22.7) and 32.7 months (95% CI: 27.8–36.3), respectively (p= <.0001) (Figure 1). The OS in patients with non-HR chromosomal abnormalities and with normal CC were 56.5 months (95% CI: 43.2–66.9) and 87.2 months (95%CI: 80.1–102.4), respectively (p= <.0001) (Figure 2). Conclusions: In this large single center study with a long follow up, we demonstrated that non-HR chromosomal abnormalities in myeloma are associated with a lower CR rate and shorter PFS and OS after auto-HCT. Further studies are needed to better define these non-HR abnormalities and their impact on prognosis. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1988-1988
Author(s):  
Prashant Kapoor ◽  
Morie A Gertz ◽  
Angela Dispenzieri ◽  
Martha Q Lacy ◽  
David Dingli ◽  
...  

Abstract Abstract 1988 Background With the utilization of novel agent-based combination therapies and autologous stem-cell transplantation (ASCT) in multiple myeloma (MM), the rigorous response category of stringent complete remission (sCR) in the international uniform response criteria is increasingly becoming attainable. In addition to the standard criteria for complete remission (CR), sCR requires normalization of the free light chain ratio and disappearance of clonal cells as determined by the marrow immunofluorescence or immunohistochemistry. We have previously validated the new response category of sCR created in by the International Myeloma Working Group and demonstrated that sCR represents a deeper level of response, translating into a superior OS. Herein we report the survival outcomes of patients attaining sCR or standard CR, from a 2-year landmark after ASCT in a cohort of patients with extended follow-up. Additionally, we report the outcome of patients who remained in sCR for at least 6 months (sustained-sCR) after ASCT. Patients and Methods Maximal response rates of four hundred and forty-five consecutive patients who underwent ASCT within 12 months of diagnosis of MM were determined. The population achieving varying degrees of complete remission (n=237) is the focus of this study. We performed a landmark analysis 2 years after ASCT to ensure that all the patients attaining at least CR had sufficient time to reach the response levels being studied. Patients were categorized as having sustained sCR (sus-sCR) if the duration of sCR was at least 6 months. Overall survival (OS) was estimated by the Kaplan Meier method and the survival curves were compared by log-rank test. Results The median follow-up of the entire cohort was seventy-seven months (95% CI: 73–82 months). The sCR rate after ASCT was 24% (n=109). Median time to progression (TTP) of patients attaining sCR was 50 months from ASCT, and median overall survival (OS) is not reached, in contrast to those attaining standard CR (n=37, TTP=20 months, OS=81 months) or near CR/nCR (n=91; TTP= 19 months, OS=60 months, p<0.0001 for both TTP and OS). OS of patients surviving at least 2 years from ASCT (Figure 1a) continued to remain superior for those attaining sCR (n=105, median: not reached) versus 70 months for the CR group (n=32; p=0.004). Among patients achieving sCR (n=109), OS of patients with sus-sCR (n= 75) at 6 months from ASCT is not reached (5-year OS=91%, 7-year OS=86%) versus median OS of 66 months (5-year OS=49%, 7-year OS=37%; p<0.0001) for those who had non-sustained-sCR (n=34) after ASCT (Figure 1b). Conclusion In our landmark analysis of patients with MM who survived at least 2 years from ASCT, those attaining sCR have a markedly superior outcome compared to those attaining standard CR. However, among patients attaining sCR, those with sustained sCR of 6 months or greater had the best outcome. Myeloma trials reporting response rates should identify patients achieving sCR and CR separately owing to markedly disparate outcomes of the two categories. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5882-5882
Author(s):  
Claudia Lucia Sossa Melo ◽  
Sara Sanguino Jimenez ◽  
Angela Peña Castellanos ◽  
Luis Antonio Salazar Montaño ◽  
Sonia Osma ◽  
...  

Abstract BACKGROUND: The scarce of unrelated donors and high costs hamper this treatment modality in Colombia. Alternative donors, such as related haploidentical donors, might contribute to a desired increase in transplant activity. OBJECTIVE: Describe sociodemographic and clinical characteristics of patients taken to haploidentical hematopoietic stem cell transplantation (HHSCT) in Fundación Oftalmológica de Santander (FOSCAL), Santander Colombia and report de early outcomes for overall survival (OS) at 100 days and 1 year of follow up. METHODS: We reviewed 11 patients taken to (HHSCT) at our institution between January 2014 and April 2016. Patients were eligible for (HHSCT) if they did not have an HLA matched related or 10/10 matched unrelated donor (MUD). Conditioning therapy included a thiotepa, fludarabine and busulfan, Graft-versus-host disease (GVHD) prophylaxis was with post-transplantation cyclophosphamide, calcineurin inhibitor and mycophenolate. OS was estimated at 100 days and at 1 year of follow up. RESULTS: Since January 2014 we have conducted eleven haploidentical T-cell repleted transplants. The median age was 25 (range 16-57) years with a HCT-CI score of 0 in 9/11 (81%) of patients and score 1 in 2/11 (19%). The ECOG performance status was 0 in 9/11 (81%) and 2/11 (status 1-2). Seven patients (63%) were male and 4 (37%) were female. Conditioning therapy with thiotepa, fludarabine, busulfan was utilized in 10/11 (90%) of patients and fludarabine, busulfan without thiotepa was utilized in 1/11 (10%) patient. The majority of patients had acute lymphoblastic leukemia 7 (63%), followed by acute myeloid leukemia 2 (18%), myelodysplastic syndrome 1 (9%) and 1 patient (9%) had acute leukemia mixed phenotype and the other one Hodgkin disease. At the time of transplant 10 patients (90%) were in complete remission, whereas 1 patient (9%) with myelodysplastic syndrome was treated with intent to achive remission, but no complete remission was achived. The majority of patients (90%) achieved 100% donor chimerism at day +28. The median time to neutrophil ≥ 0,5 x 109/L was 18 days (range 13-29) and platelets ≥ 20 x 109/L was 22 (range 10-110). Acute GVHD was seen in seven patients. Five were classified as grade II, one patient as grade I and other one as grade III. Chronic GVHD of mild severity was observed in five patients. The major post transplant complication causing significant morbidity and prolonged hospitalization was hemorrhagic cystitis (HC). It appeared as complicated grade III disease in two patients and both had evidence of co-infection with polyomavirus, adenovirus and CMV. Evidence of CMV reactivation was detected in 7 patients successfully eradicated. Evidence of EBV viremia/reactivation was found in 6 patients of whom three patients were treated with rituximab (Table 1). The OS within a median follow up of 12 months was 100%. Two patients with B-ALL and Hodgkin disease relapsed, 13 and 10,7 months post-transplantation respectively. CONCLUSION Although few patients, this type of transplant is an alternative for our patients without HLA-matched donor available, with low mortality and similar complications and outcomes to those using other donor types in high-risk hematologic disease. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1126-1126
Author(s):  
Philippe Moreau ◽  
Frederic Garban ◽  
Michel Attal ◽  
Mauricette Michallet ◽  
Gerald Marit ◽  
...  

Abstract The IFM99-03 and IFM99-04 trials were conducted from April 2000 to August 2004. Patients younger than 66 years with high-risk (b2microglobulin &gt; 3 and chromosome 13 deletion by FISH analysis at diagnosis) de novo multiple myeloma (MM) were included and prospectively treated. In both protocols, induction regimen consisted of VAD (4 courses) followed by melphalan 200 mg/m2 (HDM200) plus autologous peripheral blood stem cell transplantation (ASCT). When a HLA-sibling donor was available, ASCT was followed by reduced-intensity conditioning regimen (RIC) allograft (fludarabine, antithymocyte globulin and low dose busulfan): IFM9903 protocol (Garban et al, Blood2006;107:3474–3480). When no donor was available, patients were randomised to receive a second ASCT with HDM220 +/− anti-IL6 monoclonal antibody (BE-8, 250 mg total dose, Diaclone Besançon, France): IFM99-04 protocol (Moreau et al, Blood2006;107:397–403).284 patients met eligibility criteria and received at least one course of VAD. 65 had an available HLA-identical sibling donor and were included in the IFM99-03 trial, and 219 were included in the IFM 99-04 trial. Patients were older in the tandem ASCT trial (median age, 58 vs 54 years; P = .006) and the b2-microglobulin level was also higher in the latter group (median, 4.9 mg/L vs 4.1 mg/L; P = .049). At the reference date of July 1st, 2008, on an intent-to-treat basis, considering the entire population of 284 patients, with a median follow-up of 56 months, the EFS did not significantly differ from tandem ASCT to single autograft followed by allo-RIC (median 22 vs 19 months, P = 0.58). Nevertheless, there was a trend for a superior OS in the double ASCT trial (median 48 vs 34 months, P = 0.07). When considering the comparison of the results of the 166 patients /219 who completed the whole tandem ASCT protocol with those of the 46 patients /65 who underwent the entire auto/allo-RIC program, no difference was observed regarding EFS (median 25 vs 21 months, P = 0.88), but there was again a trend for a superior OS in favour of double ASCT (median OS, 57 vs 41 months, P = 0.08), due to a longer survival after relapse in the tandem ASCT arm. These long-term results indicate that, in a subgroup of high-risk patients with de novo MM, a tandem autologous transplant procedure is at least equivalent or even superior to a combination of autologous followed by RIC allogeneic stem cell transplantation.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1992-1992 ◽  
Author(s):  
Guenther Koehne ◽  
Heather Landau ◽  
Hani Hassoun ◽  
Alex Lesokhin ◽  
Nikoletta Lendvai ◽  
...  

Abstract Abstract 1992 Allogeneic hematopoietic stem cell transplantation (allo HSCT) is a curative therapy for patients (pts) with multiple myeloma, but conventional allo HSCT has been associated with unacceptably high rates of mortality. Non-myeloablative allo HSCT has resulted in high rates of acute and chronic graft-versus-host disease (GvHD) and progression. We report results of a pilot study of 13 pts, using T-cell depleted allo HSCT (allo TCD HSCT) from HLA compatible (matched related = 8, matched unrelated = 3, and mismatched unrelated = 2) donors. All 13 pts had relapsed myeloma within 12 mos following auto HSCT, and 12/13 pts also had high-risk cytogenetics at diagnosis [t(4;14), t(14;16), del17p by FISH and/or del13q by karyotyping]. All pts achieved at least a partial response from preceding chemotherapy or second auto HSCT. Pts underwent allo TCD HSCT with busulfan (0.8mg/kg × 10 doses), melphalan (70mg/m2 × 2 days), fludarabine (25mg/m2 × 5 days) and rabbit ATG (2.5mg/kg × 2 days). T-cell depletion was performed by positive CD34 selection (Isolex) followed by rosetting with sheep erythrocytes, achieving < 103CD3+/kg for all grafts. All pts engrafted promptly (median d+11, range d+10 to +12). Pts were eligible to receive low doses of donor lymphocyte infusions (DLI) (5×10e5 – 1×10e6 CD3+/kg) no earlier than 5mos post allo HSCT. 9/13 pts are alive and now 19–45months (mos) post TCD HSCT. Four pts are in complete remission (CR) at 19, 22, 33 and 39mos following allo TCD HSCT. Two of these pts reentered CR following DLI. Two pts had stable VGPR for 24 and 26mos before progression and reentered VGPR following treatment with Rev/Vel/Dex (RVD) + DLI; they are now 36 and 45mos post TCD HSCT. Two pts with refractory myeloma, who were transplanted with residual 16% and 10% plasma cells in marrow, achieved CR for 8 and 12mos post allo TCD HSCT before they developed progression. Following salvage chemotherapy + DLI, these pts are 20 and 21mos post transplant, respectively. One pt remained in CR for 9mos post TCD HSCT before progression with soft tissues plasmacytomas. With salvage radiation + chemotherapy, the pt is now 20mos post TCD HSCT. The 1 and 2 year probability estimates for overall survival and progression free survival with their 95% confidence intervals are: 1-yr OS 0.69 (95% CI: 0.48, 1.0); 2-yr OS 0.69 (95% CI: 0.48, 1.0); 1-yr PFS 0.46 (95% CI: 0.26, 0.83), 2-yr PFS 0.35 (95% CI: 0.15, 0.78). 12/13 pts were without signs of GvHD, but one pt had possible superimposed gut GvHD following fulminant C diff colitis. Four pts died early post TCD HSCT (between 2–6 mos), due to oseltamivir-resistant H1N1 infection (N=1); respiratory failure secondary to infection of unknown etiology (N=1), status epilepticus (N=1), and acute cerebral hemorrhage (N=1). In summary, these results demonstrate that long-lasting disease control can be achieved with TCD HSCT in pts with multiply relapsed and refractory myeloma including those with high-risk cytogenetics. Administration of calculated, low dose donor lymphocyte infusions can induce complete remission without inducing GvHD. Pts who failed to respond to standard chemotherapy pretransplant responded to reuse of this therapy post TCD HSCT. Based on these results, we are performing a phase II clinical trial at Memorial Sloan-Kettering Cancer Center for pts with relapsed multiple myeloma following auto SCT who had high-risk cytogenetics at diagnosis or at relapse as well as for patients with high-risk cytogenetics in the upfront setting following preceding auto SCT. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3428-3428
Author(s):  
Hao Zhao ◽  
Xufei Huang ◽  
Hao Cai ◽  
Lu Zhang ◽  
Jun Feng ◽  
...  

Abstract OBJECTIVE: POEMS syndrome is a rare plasma cell dyscrasia and there is currently no standard treatment. Current treatments include melphalan, autologous stem cell transplantation (ASCT) and novel regimens. However, the efficacy of these treatments has not previously been retrospectively compared in large cohorts. Therefore, this study aims to compare the efficacy and survival of three treatment regimens in patients with POEMS syndrome in our 18-year cohort. METHODS: We retrospectively analyzed the clinical records of 347 patients with newly diagnosed POEMS syndrome who were diagnosed and treated in our hospital from January 2000 to December 2017 with complete treatment and follow-up data. Patients were divided into three groups according to the initial first-line treatment regimen: melphalan + dexamethasone (MDex, N = 79) for 9 months, autologous stem cell transplantation (ASCT, N = 165), or lenalidomide + dexamethasone for 1 year (LDex, N= 103). Hematologic complete remission rates (CRH), vascular endothelial growth factor (VEGF) complete remission rates (CRV), and neurological remission rates (RN) were compared for three regimens, as well as progression-free survival (PFS) and overall survival (OS). Hematologic complete remission was negative IFE and no FLC in serum or urine. The VEGF complete remission was normalized VEGF (<600 pg/ml). The neurological response was defined as the reduction of ONLS by more than 1 point. Remission rates were compared by Pearson ӽ 2 test or Fisher's exact test. Survival curves were plotted by the Kaplan-Meier method and tested using a log-rank test. Subgroup analyses were based on risk stratification and heterogeneous baseline characteristics between treatment groups. RESULTS: Patients in the ASCT group achieved significantly higher rates of CRV (66.2%), which were superior to the MDex group (38.5%, p = 0.001) and the LDex group (47.7%, p = 0.006). There were no significant differences in CRH and RN between the three groups: CRH (MDex 37.7% vs ASCT 49.7% vs LDex 47.5%, p = 0.244) and RN (MDex 100% vs ASCT 91.% vs LDex 93.8%, p = 0.234). However, the proportion of low risk patients in the ASCT group was significantly higher than that in the MDex and LDex groups (44.2% vs 22.8% & 26.2%, p=0.001). Therefore, we performed a subgroup analysis. Subgroup analysis showed that the CRV in the ASCT group was similar to that in MDex and LDex groups in the low-risk group (p = 0.222), but there was a significant advantage in the middle- and high-risk patients (p = 0.001). After a median follow-up of 45 months, a total of 49 deaths occurred and 50 patients developed disease progressions but remained alive. The 3-year PFS was 83.7% for MDex group, 87.9% for ASCT group, and 65.2% for LDex groups. The 3-year OS was as follows: MDex group 90.6%, ASCT group 94.4%, and LDex group 81.6%. The ASCT group achieved a better PFS than the LDex group (p = 0.003), while the three groups had no significant differences in 3-year OS (p = 0.069). CONCLUSION: All three treatment regimens have achieved good efficacy and survival in the treatment of POEMS syndrome. Compared with melphalan and lenalidomide-based regimens, patients at medium to high risk may benefit more from autologous transplantation. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1233-1233
Author(s):  
Susanne Hofmann ◽  
Lisa Müller ◽  
Stephanie Harsdorf ◽  
Christian Langer ◽  
Peter Liebisch ◽  
...  

Abstract Introduction The role of allogeneic stem cell transplantation (allo-HSCT) in the treatment algorithms for patients with multiple myeloma remains controversial although it is the only potentially curative approach currently available. Here we present the retrospective analysis of 95 allo-HSCT performed between 1994 and 2013 at Ulm University Hospital. We focused on the impact of cytogenetics, graft-versus-host disease (GvHD) and intensity of conditioning on overall survival (OS), progression- free survival (PFS), relapse and non-relapse mortality (NRM). Study population Median age at initial diagnosis was 49 years (range 25-64), median age at time of allo-HSCT was 51 years (range 26-65). Median time from initial diagnosis to allo-HSCT was 13 months (range 3-106). Indications for allo-HSCT were 1) primary allo-HSCT after induction therapy (11 pts), 2) planned tandem auto-allo-HSCT (44 pts), 3) relapse after single allo-HSCT (25 pts), 4) relapse after tandem-auto-HSCT (15 pts). The conditioning regimen in 60 pts was a reduced intensity conditioning (RIC), in 35 pts myeloablative conditioning (MAC). In 68 pts cytogenetic data were available: 13 pts were stratified into standard-, 39 pts into the intermediate- and 16 pts into the high-risk group according to the mSMART recommendations. Results: Median follow-up was 70 months (95% CI, 64,5-75,5). The estimate 1-, 2- and 5-year OS was 87,4 %, 74,7 % and 46,4 % with a median OS of 36 months (95 % CI, 19,7 -52,2). For both, RIC and MAC median OS was 36 months (95% CI, 24,4–47,6 versus 95% CI, 0-108,4). The cumulative incidence of TRM was not different for RIC and MAC but there was a trend for lower relapse in patients receiving MAC (p=0,0612). With respect to the indication for allo–HSCT outcomes were as follows: Median OS was 89 months for primary allo-HSCT, 47 months for tandem auto-allo-HSCT, 20 months for relapse after auto-HSCT and 26 months for relapse after double auto-HSCT. OS did not differ significantly. Median OS in the standard risk group was 20 months (95% CI, 6,7-33,3), in the intermediate group 41 months (95% CI, 17,3-64,7) and in the high-risk group 7 months (95% CI, 0-14,8), showing no statistical significance. 1-year OS was 61,5% vs 66,7% vs 43,8%, 2-year OS was 35,9% vs 66,7% vs 43,8% and 5-year OS was 35,9% vs 43,2% vs 11,7% (standard vs intermediate vs high risk). The median PFS was 12 months (95% CI 8,4-15,6). 1-year PFS was 49,2%, 2-year PFS 32,9% and 5-year PFS was 21,8%. PFS according to the cytogenetic aberration showed a median PFS of 20 vs 14 vs 5 months, 1-year PFS was 53,8% vs 51,3 % vs 30 %, 2-year PFS with 35,9% vs 30,8% vs 7,5%, and 5-year PFS with 26,9% vs 11,5 % vs 7,5% (standard vs intermediate vs high risk). These differences are not statistically significant. Considering the impact acute GvHD, OS significantly differed between the groups with no aGvHD or aGvHD grade I and aGvHD grade II-IV with inferior survival for patients suffering from aGvHD grade II-IV. Chronic GvHD had no impact on outcome. Conclusion Our data of a 19 year experience in treatment of patients with advanced multiple myeloma with allo-HSCT showed an effective treatment option with a curative potential even for patients after intensive pretreatment including autologous stem cell transplantation. Patients who received MAC had a trend for lower cumulative incidence of relapse compared to RIC without increasing TRM in our study. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1133-1133
Author(s):  
Purvi Gada ◽  
Todd Defor ◽  
Daniel J. Weisdorf ◽  
Jeffrey S. Miller ◽  
Paul J. Orchard ◽  
...  

Abstract Burkitts Lymphoma (BL) is a highly aggressive form of non-Hodgkins lymphoma (NHL) that accounts for 50% of childhood cases of NHL, yet is rare in adults. B symptoms, advanced stage and extranodal disease are risk factors previously associated with poor survival. Hematopoietic stem cell transplantation (HCT) is often used because of either incomplete or short duration of remission with standard therapy yet little published data for HCT and BL exists. We evaluated the comparative safety and efficacy of a cyclophosphamide/total body irradiation-containing myeloablative conditioning regimen followed by either an autologous HCT (autoHCT) or allogeneic related donor HCT (alloHCT) in 38 patients who received transplants between October 1975 and June 2004. Twenty-five patients (median age 16 years [range, 4–65]) underwent an autoHCT; 13 patients (median age 13 [range, 4–62]) received an alloHCT. The median number of conventional chemotherapy regimens prior to transplant was 2 (range 1–4); the median duration of first complete remission (CR) was 0.4 years (range, 0–8.8). The majority of patients were in a complete remission (CR) at transplant (auto HCT - 16 [64%] [40% CR1]), alloHCT - 9 [69%] [23% CR1]). Patient demographics, disease characteristics at diagnosis, at relapse and at transplant were comparable between the two groups except for a greater incidence of high risk factors, including B symptoms, advanced stage at diagnosis, and extranodal (bone marrow and central nervous system) disease in the alloHCT group. The median follow up is 7 years (range 1–12) and 24 years (range 2–27) for the autoHCT and alloHCT groups, respectively. Post-transplant, 71% of auto-HCT and 75% of the alloHCT recipients obtained a CR. The 1-year treatment related mortality (TRM) was comparable in the two groups: 8% and 15% for the autoHCT and alloHCT groups, respectively (p=NS). Ten-year progression free survival (PFS) was 21% (95% CI, 4–38%) and overall survival (OS) 23% (95% CI, 5–41%) after autoHCT compared to 31% (95% CI, 6–66%) and 31% (95% CI, 6–66%) for alloHCT (p=NS). Six patients in autoHCT group and 3 in alloHCT survive disease free between 1 and 27 years; 5 survive beyond 10 years and 3 beyond 15 years from HCT. Donor choice did not significantly alter PFS. Two factors were predictive of superior PFS: fewer chemotherapy regimens prior to transplantation (1 vs ≥ 2) and CR (vs relapsed/persistent disease) at time of transplant. Patients with high risk factors more commonly underwent alloHCT, yet outcomes were comparable to autoHCT, suggesting that a powerful and durable graft versus lymphoma effect exists. These results demonstrate that prolonged remissions can be obtained with either auto or alloHCT, especially for high risk patients in CR. New approaches for patients in relapse are needed to improve these outcomes.


Sign in / Sign up

Export Citation Format

Share Document