Autologous Stem Cell Transplantation (ASCT) for the Treatment of Patients with Waldenstrom’s Macroglobulinemia / Lymphoplasmacytic Lymphoma (WM/LPL). a Risk Factor Analysis By the European Society for Blood and Marrow Transplantation (EBMT) Lymphoma Working Party

Abstract WM/LPL is a rare distinct indolent lymphoma and the optimal management of the disease remains a major challenge. Combination therapies with old and novel agents have markedly improved the response rates and the quality of response but still the CR rates remain low and so far there is no cure. The role and timing of ASCT in the management of patients with WM/LPL has not been well established. The aim of the present study was to investigate the outcome of ASCT in early vs late WM/LPL. Methods: Eligible for this retrospective study were all patients who had a first ASCT for WM/LPL between 1995 and 2011 and were registered with the EBMT database. Baseline patient, disease, and transplant data were collected from MED-A forms. Statistical analysis used log rank tests to assess the impact of baseline characteristics on survival endpoints. Overall survival (OS) and disease-free survival (DFS) was estimated from the time of ASCT using Kaplan-Meier product-limit estimates. Curves of cumulative of non-relapse mortality (NRM) and incidence of relapse (IR) were compared by Gray’s test in a competing risk framework. Results: Altogether 615 patients fulfilling the inclusion criteria were identified in the database. The median age at ASCT was 53 years (range 19-76), and 428 patients (70%) were male. The median time from diagnosis to ASCT was 19 months (interquartile range: 10-51 months). 537 patients (71%) underwent ASCT after 2002. Disease status at ASCT was first partial (PR1), very good partial (VGPR1) or complete remission (CR1) in 325 patients, whilst 176 patients were autografted in second, third or later response, and 47 patients (4%) had primary refractory or progressive disease at ASCT. High-dose therapy was TBI-based in 82 patients (14%), and stem cell source was from peripheral blood in 598 patients (97%). With a median follow-up of surviving patients of 53 months, the 5-year OS was 65%, DFS was 46%, IR was 47% and NRM was 7%. IR was significantly lower in patients receiving ASCT in first response (CR1, VGPR1, PR1) compared to transplantation in subsequent complete or partial responses or with refractory disease (39% vs 53%; p=0.001), translating into a significant DFS (50% vs 40%, p= 0.004) and OS benefit (71% vs 63%; p= 0.033) for the patients transplanted early. DFS was significantly better for patients receiving ASCT after year 2000 compared to the patients transplanted before (p=0.031) and although the year of ASCT had influence on the OS this did not reach statistical significance (p=0.068). Multivariate analysis considering age, sex, disease status at ASCT, and ASCT year confirmed ASCT beyond 1st remission (HR 1.37, 95%CI 1.04-1.79), along with female gender (HR 0.73, 95%CI 0.54-0.97) and ASCT between 2001-2005 (vs before 2001; HR 0.66, 95%CI 0.47-0.92) as significant predictors of DFS. Conclusions: These results suggest that ASCT is a feasible and effective treatment for WM/LPL. Factors predicting for a favourable DFS are female gender, transplantation in the rituximab era, and ASCT in first remission. However, with DFS and OS of 40% and 63% at 5 years, even the outcome of patients undergoing ASCT with advanced disease is still encouraging. As single-hit ASCT can induce long term response with relatively low toxicity and economic burden, it may serve as benchmark for the upcoming novel targeted therapeutics entering the WM / LPL treatment arena. Disclosures No relevant conflicts of interest to declare.

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Impact of Amotosalen/UVA Pathogen Inactivated Platelet Components on Outcomes after Allogeneic Hematopoetic Stem Cell Transplantation: A Single Center Analysis

Blood ◽

10.1182/blood-2019-122330 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1167-1167

Author(s):

Andreas S. Buser ◽

Laura Infanti ◽

Andreas Holbro ◽

Joerg Halter ◽

Sabine Gerull ◽

...

Keyword(s):

Stem Cell ◽

Cox Regression ◽

Univariate Analysis ◽

Conditioning Regimen ◽

Disease Status ◽

Risk Scores ◽

Employment Equity ◽

Stem Cell Source ◽

Equity Ownership ◽

The Impact

Background: Platelet component (PC) transfusion is required for allogeneic hematopoietic stem cell transplantation (HCT) recipients. Contamination with infectious pathogens (bacteria, viruses, or protozoa) and T-cells is a risk factor for transfusion-transmitted infection (TTI) and transfusion associated graft-versus-host disease (TA-GVHD). Pathogen inactivation (PI) treatment of PC with amotosalen-UVA (PI-PC, INTERCEPT Blood System, Cerus Corp) in platelet additive solution (PAS) without bacterial screening, gamma irradiation, CMV serology, and with 7-day storage has been the standard of care in Switzerland since 2011 to manage risk of TTI and TA-GVHD. PI-PC have replaced conventional PC (C-PC) prepared in PAS with gamma irradiation and 5 day storage. We previously reported platelet usage in two consecutive five year periods at the University Hospital of Basel. Mean PI-PC dose was higher (3.0 vs. 2.8 x 1011, p=0.001) and mean storage duration longer (4.2 vs. 3.4 days: p=0.001) than with C-PC. PC expiration wastage was reduced with 7-day PI-PC storage vs. 5-day storage (1.5% vs. 8.7%). For HCT recipients, days of PC support; PC use per patient; and RBC use per patient were similar, despite 24.3% lower corrected count increments (CCI) with PI-PC. Now, we report the impact of these observations on treatment related mortality (TRM) and overall survival (OS) 100 days after HCT. Patients and Methods: A two-period retrospective cohort study was conducted to evaluate PI-PC impact on outcomes of consecutive first allogeneic HCT recipients from January 2006 to December 2010 (Period 1, P1), when gamma-irradiated apheresis C-PC were used, and Period 2 (P2) from January 2011 to December 2017, when apheresis and whole blood-derived PI-PC were used. The review utilized 100-day OS and 100-day TRM to determine the impact of PI-PC on HCT outcomes. Descriptive statistics were used for continuous variables and log-rank analysis for survival outcomes. Univariate analysis was performed using Pearson χ2 statistics. Multivariate Cox regression modelling analyses included: PC period (P1, P2), donor match (HLA identical/twin, matched related, matched unrelated), disease state (early, intermediate, late), and conditioning regimen (reduced intensity, myeloablative) with TRM as the outcome. This was an IRB approved single-center analysis. Results: In P1 and P2, 256 and 557 consecutive first-time allogeneic HCT recipients were included, respectively. By univariate analysis, the distribution of European Group for Bone Marrow Transplantation (EBMT) risk scores (grouped 0-2, 3-4, 5-7) and mean patient age were higher during P2 (p = 0.001 and p <0.001, respectively). Primary disease status (p = 0.039); stem cell source (p <0.001); GVHD prophylaxis with ATG (p <0.001); total body irradiation (p <0.001); and conditioning regimen (p <0.001) were different between P1 and P2. Donor match (p=0.084) and disease status (p = 0.628) were similar in P1 and P2. TRM at day 100 post HCT was significantly less (31/557, 5.5%) for PI-PC recipients in P2 vs. C-PC recipients in P1 (37/256, 14.5%, p<0.001). Overall proportion of survivors at day 100 post HCT was significantly greater for PI-PC recipients (507/557, 91.0 %) compared to C-PC recipients (209/256, 81.6%, p <0.001). By multivariate Cox regression analysis, P2 with PI-PC component support was associated with improved TRM (p = 0.001; adjusted hazard ratio 0.433; 95% confidence interval: 0.262, 0.716). Donor match (p = 0.019), disease state (p = 0.022), and myeloablative conditioning (p = 0.034) were associated with significantly poorer TRM (Table). Stem cell source was not significant (p=0.157) in the model. Hemorrhage was reported as cause of death in 1/50 (2.0%) patients during P2 with PI-PC and 4/47 (8.5%) patients during P1 with C-PCs. Conclusions: Universal implementation of PI-PC in routine with extended storage to 7 days in P2 was associated with reduced TRM and better overall survival 100 days post HCT, despite transplantation of older patients with higher EBMT risk scores. Multivariate analysis revealed an adjusted hazard ratio of 0.433 (95% C.I. 0.262, 0.716) for TRM by 100 days, suggesting better outcomes in P2. This retrospective analysis at a single site indicated that PI-PC treated with amotosalen /UVA stored up to 7 days did not have a negative impact on TRM and OS in HCT recipients, and was an integral part of improving clinical outcomes at our institution. . Table. Disclosures Heim: Novartis: Research Funding. Irsch:Cerus Corporation: Employment, Equity Ownership. Lin:Cerus Corporation: Employment, Equity Ownership. Benjamin:Cerus Corporation: Employment, Equity Ownership. Corash:Cerus Corporation: Employment, Equity Ownership.

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Allogeneic Stem Cell Transplantation from Unrelated Donors after Reduced Intensity Conditioning in Patients with MDS/sAML. A Report from the Chronic Leukemia Working Party (CLWP) of the EBMT.

Blood ◽

10.1182/blood.v104.11.5176.5176 ◽

2004 ◽

Vol 104 (11) ◽

pp. 5176-5176 ◽

Cited By ~ 2

Author(s):

Nicolaus Kroeger ◽

Ronald Brand ◽

Rodrigo Martino ◽

Philippe Guardiola ◽

Anja van Biezen ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Univariate Analysis ◽

Conditioning Regimen ◽

Disease Free Survival ◽

Working Party ◽

Stem Cell Source ◽

Unrelated Donors

Abstract We analysed the results of 67 patients with MDS/sAML who were transplanted with allogeneic stem cell transplantation from unrelated donors after a reduced intenisity conditioning and reported to the EBMT. The median age was 52 years (range 17–70 years) and stem cell source was bone marrow (n = 30) or peripheral blood progenitor cells (n = 33).. The graft was HLA matched in 57 patients while 8 patients received SCT from HLA-mismatched donor. The MDS classification was as follows: RA/RARS: n=8, RAEB/CMML: n = 14, RAEB-t/sAML: n = 22. The conditioning regimen consisted of fludarabine/busulfan (n=15), fludarabine/melphalan (n=6), fludarabine and TBI (n=8) or fludarabine and others (n=36)At time of transplantation only 12 (18%) were in first complete remission. The Kaplan-Meier estimates of the probability of 2 years overall and disease free survival were 33 % (95% CI: 21–45 %) and 24 % (95% CI: 12–36 %), respectively. The probability of relapse at two years was 58 % (95% CI: 40–76 %) and of one year treatment-related mortality 37 % (95% CI %: 23–51 %). In an univariate analysis assessing source of stem cells, age, disease type, T-cell depletion, and HLA-matching no factor was significant for OS, EFS, TRM and Relapse. Allogeneic stem cell transplantation after a reduced intensified conditioning followed by unrelated SCT seems to be a feasible approach in those patients who were no candidates for a standard conditioning but is associated with a considerable number of relapses.

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Allogeneic but Not Autologous Stem Cell Transplant Attenuates the Negative Prognostic Impact Dictated By Pretransplant MRD Positivity

Blood ◽

10.1182/blood.v124.21.2363.2363 ◽

2014 ◽

Vol 124 (21) ◽

pp. 2363-2363

Author(s):

Francesco Buccisano ◽

Luca Maurillo ◽

Maria Ilaria Del Principe ◽

Gottardo De Angelis ◽

Raffaella Cerretti ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Stem Cell Transplant ◽

Conflicts Of Interest ◽

Disease Free Survival ◽

Autologous Stem Cell Transplant ◽

Poor Performance Status ◽

Prognostic Impact ◽

Cell Transplant ◽

The Impact

Abstract Multiparametric flow cytometry (MPFC) detection of minimal residual disease (MRD) represents a robust surrogate for the quality of complete remission (CR) and reliably predicts clinical outcome. In our experience, MRD detection provides prognostically relevant information when assessed at the post-consolidation time point. Ten years ago we demonstrated that the amount of MRD before autologous stem cell transplant (AuSCT) affected outcome. More recently, other authors have extended this observation to allogeneic stem cell transplant (ASCT) showing that pre-transplant MRD is a major determinant of prognosis regardless of graft-versus-leukemia (GVL) effect. The aim of our study was to evaluate, in an extended series of patients submitted to AuSCT or ASCT, the impact of a pre-transplantation MRD positive (MRDpos) or negative (MRDneg) status on overall survival (OS) and disease free survival (DFS). We analyzed 173 MRDpos and 53 MRDneg patients of whom 67 were submitted to AuSCT and 51 to ASCT. Eighty-two patients received no transplant because of age, poor performance status or insufficient stem cell harvest whereas 26, all in the MRDpos group, relapsed before transplant delivery. In the AuSCT group, before transplant, 32/67 (48%) were MRDneg and 35/67 (52%) MRDpos, with MRDneg group showing a superior OS (55% vs 20%, p=0.007). In the ASCT group, before transplant, 45/51 (88%) were MRDpos and 6/51 (12%) MRDneg. For 21 out of 51 (41%) sources of stem cells were matched unrelated donors (12) or haploidentical donors (9). In this subgroup, MRDpos and MRDneg patients shared a comparable 5-years OS (60% vs 56%, p=NS), with a 36% survival gain for those MRDpos who received ASCT as compared to AuSCT. Among MRDneg patients, no survival differences were demonstrated between those submitted to AuSCT or ASCT (55% vs 60%, p=NS). Such a lack of difference is likely due to the higher treatment related mortality (ASCT 3/6, 50% vs AuSCT 2/32, 6%, p=0.003) which counterbalanced the lower relapse rate in the ASCT group (ASCT 0/6, 0% vs AuSCT 11/32, 34%, p=NS). In conclusion, ASCT confers a significant survival advantage to MRDpos patients, attenuating the negative prognostic impact of pre-transplant MRD positivity. ASCT may expose MRDneg patients to an excess of toxicity suggesting that in these patients the allogeneic option should be postponed after a second remission. In MRDpos patients, AuSCT does not represent a valid therapeutic choice and ASCT, which should be timely delivered, also considering alternative sources of stem cells. Disclosures No relevant conflicts of interest to declare.

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The Influence of PET/Gallium (PET/Gal) Status and High-Dose Rituximab (HDR) in Patients with Aggressive, Large, B-Cell Lymphoma (LBCL) Receiving Autologous Stem Cell Transplants (ASCT).

Blood ◽

10.1182/blood.v108.11.3058.3058 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3058-3058 ◽

Cited By ~ 1

Author(s):

Amin M. Alousi ◽

Rima M. Saliba ◽

Grace-Julia Okoroji ◽

Chitra Hosing ◽

Barry I. Samuels ◽

...

Keyword(s):

Multivariate Analysis ◽

Stem Cell ◽

De Novo ◽

Univariate Analysis ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

Disease Status ◽

High Dose ◽

Free Survival ◽

The Impact

Abstract Background: PET/Gal status has been reported to be an important predictor of outcome in patients with LBCL who receive an ASCT. Newer conditioning regimens which include high-dose rituximab (HDR) have been shown to improve results (Khouri, JCO, 2005). The impact of HDR on the outcome of patients based on PET/Gal status has not been determined. Methods: A retrospective review of patients with chemo-sensitive, LBCL who received an ASCT on a research protocol at MD Anderson between 1995 and 2005 was performed. Factors that were considered for outcome included: Age, IPI, # of prior chemotherapies, B2-microglobulin, disease status at transplant, HDR and PET/Gal status. In patients who received HDR, it was given with stem cell mobilization and then again on days +1 and +8 following transplant. Results: A total of 188 patients were identified. Median age was 49 years with 108 (57%) male patients. 147 patients (78%) had de novo LBCL and 41 (22%) had a LBCL of follicular origin (LBCL-F). 83 (39%) patients received HDR. At transplantation, 95 patients (50%) were in PR, 71 (38%) in CRU and 22 (12%) in CR. 142 (76%) patients were PET/Gal negative, 37 (20%) PET/Gal positive and 9 (4%) were unknown. Median follow-up was 47 months. On multivariate analysis, for patients with de novo LBCL, PET/Gal status and HDR were the only predictors for progression and progression free survival (PFS). Patients who were PET/Gal negative and those that received HDR had a hazard ratio (HR) of 0.3 (p<0.001) and 0.5 (p=0.02) for progression, respectively (see the table below for the cumulative incidence (CI) for progression and PFS at 54 months according to HDR and PET/Gal status for de novo LBCL undergoing ASCT). PET/Gal Status and HDR were also found to be predictive for patients with LBCL- F on univariate analysis, however due to the small numbers in this subset; multivariate analysis could not be performed. PFS at 54 months for patients with LBCL-F who were PET/Gal negative was 40% versus 17% in the PET/Gal positive group, (p=0.006). PFS for those LBCL-F patients who received HDR was 81% as compared to 23% for those who did not receive HDR, (p=0.007). Conclusions: The two most important predictors of outcome following ASCT are PET/Gal status and whether HDR was given with the transplant regimen. The addition of HDR to the transplant regimen decreases the risk for progression irrespective of PET/Gal status; however the improvement is more significant in patients with a negative PET/Gal scan. C.I. for progression and PFS at 54 months for de novo DLBCL PET/Gal Status HDR CI of Progression (%) Progression Free Survival Positive No 83 17 Positive Yes 54 45 Negative No 35 55 Negative Yes 22 75

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Reduced Intensity Versus Conventional Myeloablative Conditioning (RIC vs. MAC) Allogeneic Stem Cell Transplantation (allo-SCT) for Patients with Acute Lymphoblastic Leukemia (ALL): A Survey from the Acute Leukemia Working Party of EBMT

Blood ◽

10.1182/blood.v112.11.793.793 ◽

2008 ◽

Vol 112 (11) ◽

pp. 793-793 ◽

Cited By ~ 2

Author(s):

Mohamad Mohty ◽

Myriam Labopin ◽

Tapani Ruutu ◽

Alois Gratwohl ◽

Gerard Socie ◽

...

Keyword(s):

Stem Cell ◽

Cumulative Incidence ◽

Negative Impact ◽

Therapeutic Option ◽

Lymphoblastic Leukemia ◽

Working Party ◽

High Dose ◽

Adult Age ◽

Stem Cell Source ◽

Significant Difference

Abstract The exact role of RIC allo-SCT for adult patients with ALL is still under considerable debate. While the use of such so-called nonmyeloablative or RIC regimens has emerged as an attractive modality to decrease transplant-related mortality, toxicity might represent only one aspect of the problem, since ALL encompasses a group of chemosensitive diseases, raising concerns that significant reduction of the intensity of the preparative regimen may have a negative impact on long-term leukemic control. In this multicenter retrospective study, the outcomes of 601 adult (age at transplantation >45 y.) patients with ALL who underwent transplantation in complete remission (CR) with an HLA–identical sibling donor, were analyzed according to 2 types of conditioning: RIC in 97 patients, and standard MAC (or high-dose) in 504 patients. Both groups were comparable in terms of gender, CR status (CR1 and CR2), interval from diagnosis to allo-SCT, and recipient/donor CMV serostatus. Patients in the RIC groups were older (median 56 y. vs. 50y in the MAC group; P<0.0001), Most of the patients in the MAC group received high dose TBI (80%), while the majority of the RIC regimens included either low-dose TBI or were ATG+chemotherapy-based regimens. The majority of patients (88%) from the RIC group received a PBSC graft. In the MAC group, the stem cell source consisted of bone marrow in 42% of patients. With a median follow-up of 13 months (range, 1–127), the incidences of grade II-IV and grade III-IV acute GVHD were: 35%, 14%, and 28%, 10% in the MAC and RIC groups respectively (P=NS). The cumulative incidence of non-relapse mortality at 2 years (NRM) was 32% (MAC) vs. 22% (RIC) (P=0.04). The cumulative incidence of relapse at 2 years was 30% (MAC) vs. 42% (RIC) (P=0.0007). However, the latter differences did not translate into any significant difference in term of leukemia-free survival (LFS) at 2 years: 38% (MAC) vs. 37% (RIC) (P=0.42). In multivariate analysis for LFS, the status at transplant was the only factor associated with an improved LFS (p<0.0001, RR=0.55, 95%CI, 0.42–0.72). The results of this retrospective registry based study suggest that RIC regimens may reduce NRM rate after allo-SCT for adult ALL when compared to standard MAC regimens, but with a higher risk of disease relapse and no impact on LFS. The latter represent promising findings, since patients who received RIC are likely to have serious comorbidities, which led the transplantation center to choose RIC, and surely most of these patients would not have received a standard allo-SCT in most institutions. Therefore, RIC allo-SCT for adult ALL (>45 y.) may represent a valid therapeutic option when a conventional standard conditioning is not possible, warranting further prospective investigations.

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The Roel of High Dose Chemotherapy and Autologous Stem Cell Transplantation (ASCT) In PATIENTS with POEMS SYNDROME: A Retrospective study of the MM Subcommittee of the Chronic Leukemia Working Party of the EBMT,

Blood ◽

10.1182/blood.v118.21.4115.4115 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4115-4115 ◽

Cited By ~ 1

Author(s):

Gordon Cook ◽

Laurent Garderet ◽

Anja van Biezen ◽

Anja Henseler ◽

Véronique Leblond ◽

...

Keyword(s):

Plasma Cell ◽

Conflicts Of Interest ◽

Conditioning Regimen ◽

Working Party ◽

Poems Syndrome ◽

Plasma Cell Dyscrasia ◽

Bone Lesions ◽

High Dose ◽

Engraftment Syndrome ◽

The Impact

Abstract Abstract 4115 Introduction: Polyneuropathy, organomegaly, endocrinopathy, skin changes associated with a paraproteinaemia (POEMS syndrome) is a rare paraneoplastic syndrome secondary to a plasma cell dyscrasia. Effective treatment, including ASCT, of the underlying plasma cell dyscrasia can control the disease and often dramatically control symptoms. Limited data is available for ASCT in POEMS. Specific Aim: The aim of this study was to describe the clinical outcome of ASCT for patients with POEMS syndrome, determining the impact of patient and disease-specific factors on prognosis. The incidence of engraftment syndrome and the presentation of relapse were examined. Methodology: Patient-, disease-, and transplant-related variables were collected according to the data entries in the EBMT database, including tracking incomplete data entries from participating centers. Results: 116 patients underwent an ASCT between 1997–2009 and satisfied the entry criteria. The median age was 50 yrs (range 26–69) with 56.8% of patients '50 year of age. 58.6% had peripheral neuropathy, 66.2% volume overload, 48.3% had organomegaly, 19.8% had papiloedema, 46.6% had dermopathies and 34.5% had sclerotic bone lesions at presentation. The median time from diagnosis to ASCT was 7.8 mns (range 1–346) with 34.5% of patients receiving an ASCT >12 months from diagnosis. The graft source was PBSC in 100% of patients. Disease status at ASCT was: 32% CR/PR, 30% SD/MR/untreated and 5 in PD. Missing information on stage in 33% of the cases. The conditioning regimen was Melphalan ≥200mg/m2 in 52.5%, Melphalan <200mg/m2 in 9.3% (38.1 of data on dose is missing) and TBI-containing only 1 patient. Engraftment was seen in 112 (96.6%) patients with failed engraftment reported in 3 patients (2.5%). Details of the occurrence of engraftment syndrome are currently under collection and analysis though peri-engraftment fever was reported in 23.4% and pulmonary infiltrates in 4.8%. Haematological response was characterized as CR in 31%, PR in 20.7%, <PR in 20.7% and currently unknown in 27.6%. Best disease response, in terms of end-organ response is under evaluation. With a median follow-up of 30.1 mns (range 0.1–161), 90.5 % of patients are alive and only 8.6% of patients have relapsed. The non-relapse mortality was 6.9%. Causes of death: 5 died of infection, 2 from graft failure, 1 from cardiac toxicity. The 3-year probabilities of PFS and OS are 82% and 94%, respectively. The 5-year probabilities of PFS and OS are 80% and 92%, respectively. The data analyzed in this study, to-date, demonstrates that ASCT can be an effective and safe therapeutic modality for patients with POEMS syndrome. The role of high dose therapy compared with more conventional dose therapies warrants further investigation. Disclosures: No relevant conflicts of interest to declare.

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Incorporating Target Immunotherapy into Standard Conditioning Regimen Prior to Autologous Stem Cell Transplantaion (ASCT) Improves the Transplant Outcome for Pateints with Relapsed/Refractroy B Cell Non-Hodgkin Lymphoma (B-NHL).

Blood ◽

10.1182/blood.v110.11.1911.1911 ◽

2007 ◽

Vol 110 (11) ◽

pp. 1911-1911

Author(s):

Mohamed I. Farhat ◽

Reem Karmali ◽

Stephanie A. Gregory ◽

Parameswaran Venugopal ◽

Mohamad Kassar ◽

...

Keyword(s):

Stem Cell ◽

Disease Progression ◽

Conditioning Regimen ◽

Disease Free Survival ◽

High Dose Chemotherapy ◽

High Dose ◽

Cell Transplant ◽

Free Survival ◽

The Impact ◽

Disease Free

Abstract Background: Refractory or relapse B-NHL has a poor prognosis with conventional chemotherapy. Autologous stem cell transplant (ASCT) preceded by high dose chemotherapy has been the preferred therapeutic choice for such patients. The majority of the treatment failures occur within one to two years post transplant with disease progression after transplant accounted for most of the failures. The incorporation of targeted immunotherapy (rituximab) into the upfront and relapse setting is becoming of the standard of care for patients with B-NHL. The objective of this study is to evaluate the impact of rituximab (R) on disease free survival (DFS) when added to a standard conditioning regimen -- BEAM (carmustine, cytarabine, etoposide, and melphalan) prior to ASCT. Methods: A single institution retrospective analysis of 53 patients (pts), whom were heavily pre-treated, underwent ASCT between 08/98 & 07/06. All pts received rituximab in combination with high dose cytoxan for stem cell mobilization. 37 pts received R-BEAM and 16 received BEAM prior to ASCT. Actuarial rate for DFS was estimated from the day of SCT using the Kaplan-Meier method. Results: The group was predominantly men, 73% and 78%, with a median age of 57 years for both the R-BEAM and BEAM group. With a median follow up of 15.7 months, 13/37 (32%) and 11/16 (64%) pts who received R-BEAM and BEAM respectively developed disease progression after ASCT. The 2-yr actuarial disease-free survivals (figure1) were 60% and 21% for the R-BEAM and BEAM arm respectively (p=0.006). Conclusion: In this study, the outcome of pts who received R-BEAM compares favorably to those who receive BEAM alone with significant improvement in disease-free survival. Thus, incorporating target immunotherapy into standard conditioning regimen may have altered the natural history of the disease for pts undergoing ASCT for relapsed/refractory B-NHL. Disease Free survival Disease Free survival

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Birth Order Does Not Affect Outcome in HLA-Identical Sibling Transplantation.

Blood ◽

10.1182/blood.v110.11.5003.5003 ◽

2007 ◽

Vol 110 (11) ◽

pp. 5003-5003

Author(s):

Edward Copelan ◽

Ronald Sobecks ◽

Robert Dean ◽

Lisa Rybicki ◽

Stacey Brown ◽

...

Keyword(s):

Stem Cell ◽

Birth Order ◽

Acute Gvhd ◽

Chronic Gvhd ◽

Disease Free Survival ◽

Rank Test ◽

Hematopoietic Stem ◽

Stem Cell Source ◽

Male Donor ◽

The Impact

Abstract Fetomaternal and transmaternal sibling microchimerism might result in tolerance of hematopoietic stem-cell donors to recipients who were born before them. A single clinical study comparing first-born recipients and first-born donors provided evidence that birth order can have a significant impact on survival and on the incidence of acute graft-versus-host disease (GVHD) and relapse in HLA-identical sibling transplantation. In order to determine whether birth order might exert a consistent, biologically important effect, we compared survival and the incidence of acute GVHD, chronic GVHD, and relapse in recipients of HLA-identical transplants from sibling donors older than themselves to recipients with younger sibling donors. From 11/84 through 11/06, 410 first HLA-identical sibling transplants were performed. Patients were categorized by whether the sibling donor was older (n=187) or younger (n=223) than the recipient. As expected, the two groups differed with respect to patient age (P<0.001). The groups were similar with respect to gender, diagnosis, interval from diagnosis to transplant, extent of prior treatment, preparative regimen, stem-cell source, donor to patient gender, and CD34+ cell dose. Outcomes were estimated using the Kaplan-Meier Method and compared between the birth order groups using the log rank test. The incidence of acute GVHD, ≥ grade II acute GVHD, chronic GVHD, extensive chronic GVHD, relapse, survival, and disease-free survival were similar (0.39≤P≤0.85) between the two groups. The incidence of acute GVHD and survival in the two groups is shown below: Figure Figure Figure Figure After adjustment for differences between the two groups, multivariable assessment of sibling birth order was not prognostic for survival (P=.32). Only older (P=0.029) and male donor/female recipient (P=.017) were independent prognostic adverse factors. In this large study of the HLA-identical sibling transplantation, no impact of birth order on the incidence of GVHD, relapse incidence, or survival was detected. Although (because of different methodologies) not directly contradictory to a previous study of birth order, the present results suggest that further study of the impact of birth order on outcome of HLA-identical sibling transplantation is needed. Suggestions that birth order be integrated into donor-selection algorithms or that matched unrelated donors might be preferred to high-risk HLA identical siblings are premature.

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Multi-Organ Involvement of Multiple Myeloma Cells In the Cases of Recent 10 Years: A Clinicopathologic Study of 81 Consecutively Autopsied Cases

Blood ◽

10.1182/blood.v116.21.5004.5004 ◽

2010 ◽

Vol 116 (21) ◽

pp. 5004-5004

Author(s):

Shotaro Hagiwara ◽

Makoto Mochizuki ◽

Hisako Endo ◽

Risen Hirai ◽

Akira Tanimura ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Conflicts Of Interest ◽

High Dose ◽

Clinicopathological Feature ◽

Pathological Feature ◽

Myeloma Cells ◽

The Impact

Abstract Abstract 5004 Background: Despite recent progress in treatment, multiple myeloma is still uncurable disease. The impact of modern therapy on the causes of death and pathological feature of end-stage myeloma is not fully understood. Methods: We studied autopsied cases with multiple myeloma between 1979 and 2009 at National Medical Center of Global Health and Medicine, Tokyo, Japan. We compared the clinicopathological feature of the autopsied cases in recent 10 years with the cases before 2000. Statistical analysis was performed using student's t-test and chi-square test. Results: There were 81 autopsied cases between 1979 and 2009. 31 cases were autopsied in recent 10 years and the older 50 cases were before 2000. Mean age at death was 59.2 and 65.1 years old, and the mean duration of illness was 46.1 and 31.9 months, respectively. Stem cell transplantation was performed in 13 (12 autologous, 1 allogeneic) of recent cases and 3 (2 autologous and 1 allogeneic) of older cases. In recent cases, five patients were treated with bortezomib, 2 were with thalidomide and 2 were with both. Extramedullary infiltration of myeloma cells were observed in both groups. The frequent sites of involvement were spleen, liver, kidney, lymph nodes, lung, pancreas, adrenal gland and perioneum. The infiltration in liver and lung was significantly frequent in the recent cases than in the older cases (58.1% vs. 28.0%, p=0.007, and 38.7% vs. 18%, p=0.039). Infection as a cause of death was noted more frequently in the recent cases than in the older cases (41.9% vs. 18.0%, p=0.019). Amyloid deposition was detected in 16.1% and 22.0% (ns.), and myeloma kidney was noted in 48.4% and 60% (ns.). Conclusion: High dose chemotherapy with stem cell support and novel agents have been contributed to improving the survival. However, the increase in resistant bacterial and fungal infection is serious problem. Also, extramedullary relapse after autologous and allogeneic stem cell transplantation is not rare, and extramedullary progression under thalidomide has been reported. In our recent autopsied cases, the incidence of fatal infection and extramedullary involvement of myeloma cells was significantly higher than in the older cases. Disclosures: No relevant conflicts of interest to declare.

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Salvage Autologous Hematpoeitic Stem Cell Transplants (AHSCT2) for Myeloma: Single Center Experience.

Blood ◽

10.1182/blood.v116.21.4591.4591 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4591-4591

Author(s):

Bishoy Faltas ◽

Jane L. Liesveld ◽

Michael Becker ◽

Jainulabdeen J. Ifthikharuddin ◽

Gordon L. Phillips

Keyword(s):

Overall Survival ◽

Multivariate Analysis ◽

Stem Cell ◽

Median Overall Survival ◽

Progressive Disease ◽

Conflicts Of Interest ◽

High Dose ◽

The Impact

Abstract Abstract 4591 Although the role of AHSCT1 is well established in multiple myeloma therapy, the role of the salvage (not “tandem”) AHSCT2 is less clear. However, most pts. undergo initial stem cell harvests with plans for eventual AHSCT2. To clarify the indications, the prognostic factors and the outcomes of AHSCT2 in relapsed myeloma, we analyzed our experience in 19 pts. (pts.) who underwent salvage AHSCT2 between the 1994–2008. Mean age at AHSCT1/2 was 54.58 (SD 7.96)/57.03 (SD 8.10) respectively; 15 (79.0%) were males. At the time of diagnosis, 7 (36.8%) pts. had ISS stage I, 6 (31.6%) stage II, 3(15.8%) stage III and in 3 (15.8%) the ISS stage could not be determined. Isotypes: IgG 11 (57.9%), IgA 4 (21.1%), 1 (5.3%) pt. had IgM and 3 (15.8%) had light chain myeloma. Cytogenetics were normal in 6 (31.6%), abnormal in 5 (26.3%) and unavailable for 8 (42.1%) pts. The most common therapy received prior to AHSCT1 was Vincristine/Adriamycin/Dexamethasone in 11 (57.9%) pts.; 7 pts. were exposed to novel agents. One pt. achieved complete response (CR), 15 (79.0%) pts. achieved partial response (PR) and 3 (15.8%) pts. had stable or progressive disease after receiving the initial treatment. All pts. proceeded to receive high dose therapy with Melphalan (MEL), 2 pts received fTBI in addition to MEL. Mean MEL dose was 190.00 mg/m2 (SD 23.01); 15 pts. received 200 mg/m2. All pts. received >2×10e6/kg of CD34+ cells in the first and second transplants. At D+100 after AHSCT1, responses were: 4 (21.1%) CR, 1 (5.3%) VGPR, 8 (42.1%) PR and 6 (31.6 %) with lesser responses. Therapy to prolong response or for salvage after AHSCT1 was given in all pts before AHSCT2, including Thalidomide in 6 (31.6%), Bortezomib in 4 (21.1%) and Lenalidomide in 2 (10.5) pts. Median time to progression after AHSCT1 was 318 days [95 % CI 110– 573]. Median interval between AHSCT1 and AHSCT2 was 896.74 days (SD: 698.34 days). At the time of AHSCT2, 4 (21.1%) were in PR, 15 (79.0%) had progressive disease. For AHSCT2, all pts. Received MEL, one pt. received MEL + Cytoxan and one pt. received MEL + Bortezomib. The median MEL dose/m2 was 175.56 (52.04).All pts. survived AHSCT2 to D+100, responses were as follows: 3 (15.8%) VGPR, 9 (47.4%) in PR; 7 (36.9) pts. had lesser responses. After AHSCT2, nine (47.4%) pts. had grade III toxicity and only one pt. had grade IV toxicity (avascular necrosis). Maintenance therapy after AHSCT2 included Bortezomib in 7 (36.8%) pts., Lenalidomide in 5 (26.3%) pts. and Thalidomide in 4 (21.1%) pts. After AHSCT2, the median overall survival (OS) was 658 days [95 % CI 326–1330] and progression free survival (PFS) after AHSCT2 was 237 days [95 % CI 121– 397] (Figure 1). OS probability at 6, 12, 24 months after AHSCT2 was 81.3, 75.0, 39.3 % respectively. For all pts., the median OS time (i.e. time from diagnosis to death or last follow-up) was 2187 days [95% CI 1413– 4126]. At the end of the follow up period, a total of 14 pts. had died. Causes of death were progression in 12 (63.2%) and sepsis in 2 pts. (10.5%). The number of previous lines of chemotherapy, interval between transplants, disease status at the time of AHSCT1/2, type of myeloma and MEL dose were not predictive of OS and PFS. In the multivariate analysis, only age by decade at AHSCT2 and male gender were independent predictors of OS after AHSCT2 (HR 4.037, P= 0.01), (HR 3.74, P=0.07) respectively. Similarly, in the multivariate analysis for PFS after AHSCT2, age at AHSCT2 was an unfavorable independent predictor (HR 3.48, P=0.009) whereas relapse free response more than 18 months after AHSCT1 was an independent favorable predictor (HR 0.198, P=0.007).Our results are consistent with the few studies examining the impact of salvage transplants for myeloma which report a median overall survival ranging from 20.7 to 38.1 months from the time of AHSCT2.We conclude that salvage AHSCT2 can positively impact PFS and OS but efforts to improve outcomes are mandatory.FigureSEQ Figure ≂,* ARABIC 1Figure. SEQ Figure ≂,* ARABIC 1 X-axis represents time from AHSCT2 in days. Y axis represents survival distribution. Blue line = OS, Red = PFS. Disclosures: No relevant conflicts of interest to declare.

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