Tandem Autologous Hematopoietic Stem Cell Research Articles

Early results of treatment in accordance with the NB-HR-2018 protocol in patients with high-risk neuroblastoma in the Republic of Belarus

The development of new criteria for high-risk neuroblastoma treatment optimization and the introduction of new approaches to its management are a pressing problem in modern pediatric oncology. In this study, we aimed to develop and implement new high-risk and ultra-high-risk criteria, introduce tandem autologous hematopoietic stem cell transplantation (HSCT) as consolidation therapy for high-risk neuroblastoma patients as well as to assess patient tolerability of this treatment. The study was approved by the Independent Ethics Committee and the Scientific Council of the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology. In 2018, a new protocol called NB-HR-2018 was developed and implemented at the Center for Pediatric Oncology, Hematology, and Immunology (Belarus) that included new criteria defining high-risk groups. Twenty-three patients were treated according to the new protocol, with 20 of them receiving autologous HSCT. The comparison group included 56 high-risk patients who had undergone treatment in accordance with the NB 2004 protocol. Tandem autoHSCT significantly reduces the rates of underlying disease relapse/progression (p = 0.047) and demonstrates better event-free survival rates (56 ± 12% vs 36 ± 6%; р = 0.445). The use of the new high-risk criteria and the new treatment method (tandem autologous HSCT) is concluded to be a reasonable approach since it significantly reduces disease relapse rates and is well tolerated by the patients.

Obtaining M Protein Immune Reconstitution As Soon As Possible after Tandem Autologous Hematopoietic Stem Cell Transplantation Improves the Prognosis of Patients with Newly Diagnosis Multiple Myeloma

Objective: In the era of new drug therapy, autologous hematopoietic stem cell transplantation after induction therapy is the standard of care for patients with multiple myeloma, and Tandem autologous hematopoietic stem cell transplantation is a treatment option to improve the prognosis of patients with high-risk cytogenetics, and obtaining M protein immune reconstitution as soon as possible after double transplantation can further improve the survival of such patients. METHODS: A total of 12 patients with newly diagnosed multiple myeloma diagnosed from June 1, 2019 to April 30, 2021 at the First Affiliated Hospital of Sun Yat-sen University were included, and all patients underwent tandem autologous hematopoietic stem cell transplantation after induction therapy containing bortezomib, and the prognostic survival of patients who obtained M-protein reconstitution after transplantation was analyzed Results: 58.3% (7/12) of patients obtained M protein immune reconstitution after Tandem transplantation, the most common type of M protein was IgG-type M protein, the median time to obtain M protein immune reconstitution was 3 months (2-9 months) after Tandem transplantation, the median duration of reconstitution was 3 months (3-6 months), and all patients were R-ISS stage II-III, 83.3% (10/12) of patients had high-risk cytogenetics, all patients achieved at least VGPR efficacy after transplantation, with a higher CR rate in the M protein immune reconstitution group (71.4% vs 60.0%, P=0.679), although not statistically significant, and a median survival time of 2 years in the immune reconstitution group CONCLUSION: Tandem transplantation is a treatment option to improve prognosis in patients with high-risk cytogenetic multiple myeloma, and patients who received M protein immune reconstitution after Tandem transplantation significantly improved survival time.

OA-42 Second primary malignancies after tandem autologous hematopoietic stem cell transplantation for patients with multiple myeloma treated on earlier total therapy protocols

OA-42 Second primary malignancies after tandem autologous hematopoietic stem cell transplantation for patients with multiple myeloma treated on earlier total therapy protocols

P-147 Obtaining M protein immune reconstitution as soon as possible after tandem autologous hematopoietic stem cell transplantation improves the prognosis of patients with newly diagnosis multiple myeloma

P-147 Obtaining M protein immune reconstitution as soon as possible after tandem autologous hematopoietic stem cell transplantation improves the prognosis of patients with newly diagnosis multiple myeloma

Tandem autologous hematopoietic stem cell transplantation for embryonal brain tumors in infants and very young children.

Withdrawal of radiotherapy in patients with brain tumors under four years decreases chance for cure. AutoHSCT in a series of pilot studies demonstrated a potential to improve outcomes in these patients. The study included 50 patients with median age of 39 months (7-53). Medulloblastoma (n = 28, 56%), ETMR (n = 9, 18%) and other histological types (n = 13, 26%) were most commonly diagnosed. Forty two patients (84%) received tandem autoHSCT by HIT-MED protocol, and single autoHSCT was performed in eight children (16%). Adjuvant radiotherapy was administered in 25 (50%) children and treatment of relapse included radiotherapy in 6 (12%). Median follow-up was 39.6 months (6-121). Long-term CIR was 37%, and TRM - 6%. Five-year OS was 71% in medulloblastoma, 37% in ETMR and in other tumors - 51% (p = 0.07). Irradiation-free OS at 5 years for children with medulloblastoma was 24%. For the whole cohort of CNS tumors, independently of histology, OS and PFS at five years were 60% and 46%, respectively Young children with medulloblastoma, following tandem autoHSCT, demonstrate OS comparable to older children. Patients with other histological types demonstrate suboptimal long-term survival rates after autoHSCT and one should assess whether these patients benefit from autoHSCT.

The Role of Allogeneic Stem Cell Transplantation in Multiple Myeloma: A Systematic Review of the Literature.

Multiple myeloma (MM) is an indolent B-cell malignancy, where treatment is aimed at preventing organ dysfunction from light chain accumulation (slowing disease progression) and inducing remission. Allogeneic stem cell transplant (allo-SCT), through graft versus myeloma (GVM) effects, has the potential to induce remission to a potentially curative-like state. In this systematic review, we aimed to understand this relationship to the risks and severity of disease in categorized patients and gain an updated comprehension of the future of allo-SCT in MM treatment. We conducted this review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and searched the PubMed database to obtain the specified literature with both the use of keywords and Medical Subject Headings (MeSH). A total of 16 relevant articles were included for discussion after the quality appraisal was completed, as appropriate, by either the Cochrane tool or Newcastle-Ottawa checklist. Our review concludes that while allo-SCT may benefit high-risk patients, successful procedures may incorporate a tandem autologous hematopoietic stem cell transplant approach in combination with novel pharmacologic contributions for which there is an observed synergy in the modulation of the immunologic microenvironment. Furthermore, tailored patient selection by evaluating pre-transplant factors including high-risk cytogenetics, age, and pre-salvage International Staging System (ISS) can predict post-transplantation success including non-relapse mortality. Successive research should continue to revise and update treatment options as the evolving therapeutic drug regimens may change over the course of indolent disease.

Transplantation for ultra high-risk neuroblastoma patients: effect of tandem autologous stem cell transplantation

Aim: Neuroblastoma is a tumor with a high mortality rate originating from primitive sympathetic ganglion cells. In recent years, the definition of "ultra high-risk" has been used, in which the response to treatment is added in addition to the disease characteristics. In this study, the results of tandem high-dose Iodine 131 (131I) metaiodobenzylguanidine (MIBG) and tandem autologous hematopoietic stem cell transplantation (HSCT) in patients who were diagnosed as refractory after first-line treatments and considered with ultra-high risk nöroblastom (NBL) in Erciyes University Medical Faculty Pediatric Bone Marrow Transplant Center were shared.
 Material and Method: Eleven patients who underwent tandem MIBG and autologous HSCT with the diagnosis of refractory/ultra high-risk NBL between 2011 and 2021 were included in the study. Patient's data were obtained retrospectively using an electronic or manuscript medical record.
 Results: Tandem autologous HSCT and MIBG treatment were applied to 11 patients with a median age of 40.5 months who were diagnosed with refractory/ultra high-risk neuroblastoma. In our study, the overall survival rate was 54.5% and event-free survival (EFS) was 39% at a median follow-up of 20.7 (7.8-105.6) months. Of the 6 surviving patients, 4 are followed in complete remission and 2 in partial remission.
 Conclusion: Our study is the only study that includes a group of patients who received tandem high-dose MIBG and tandem autologous HSCT transplantation in refractory NBL patients without cytokine and immunotherapy. Tandem transplantation and MIBG therapy in ultra-high-risk NBL cases remain promising with acceptable toxicity. Adding immunotherapy to this treatment protocol and combining it with new treatment modalities such as anaplastic lymphoma kinase (ALK), which also takes into account genetic characteristics, may increase survival and event-free survival rates.

258 - Tandem Autologous Hematopoietic Stem Cell Transplantation with Non-Cross Resistant Conditioning Regimens for Relapsed/Refractory Germ Cell Tumors: A Long Term Follow up of a Phase II Trial at the University of Minnesota

258 - Tandem Autologous Hematopoietic Stem Cell Transplantation with Non-Cross Resistant Conditioning Regimens for Relapsed/Refractory Germ Cell Tumors: A Long Term Follow up of a Phase II Trial at the University of Minnesota

Tandem Autologous Hematopoietic Stem Cell Transplantation in Very Young Patients with Multiple Myeloma.

Introduction Multiple myeloma (MM) in very young patients is uncommon, and no treatment guidelines exist for these patients. Patients and Methods We performed a retrospective analysis of five very young myeloma patients who underwent tandem autologous hematopoietic stem cell transplantation (HSCT). Results The median age was 37 years (range = 34–40 years). A median of two leukapheresis was performed (range = 1–4). The median number of hematopoietic stem cells collected was 5.4 × 10 6 /kg (4.4–8.2 × 10 6 /kg). During first transplant, four patients received melphalan of 200 mg/m 2 and one patient received melphalan of 140 mg/m 2 (due to renal failure) as conditioning regimen. Second transplant conditioning was melphalan of 200 mg/m 2 for one patient and melphalan of 140 mg/m 2 for remaining four patients. Two patients were in complete remission, and two were in very good partial remission and one patient progressed to active disease at the time of tandem autologous bone marrow transplant. All patients developed significant mucositis. Neutrophil and platelet recovery was longer in tandem autologous hematopoietic stem cell transplant. More viral infections were seen in tandem transplant. Day 30 and day 100 mortality was nil. Conclusion We present data on tandem autologous HSCTs in very young patients with MM in India. Responses continued to improve in this small series.

Tandem Autologous Hematopoietic Stem Cell Transplantation for Treatment of Adult T-Cell Lymphoblastic Lymphoma: A Multiple Center Prospective Study in Southwestern China

Background: T-cell lymphoblastic lymphoma (T-LBL) is a highly aggressive form of lymphoma with poor clinical outcomes and lack of a standard treatment regimen. Accordingly, this study evaluated the safety and efficacy of tandem autologous hematopoietic stem cell transplantation (auto-HSCT) treatment for adult T-LBL and assessed factors affecting survival. Methods: Newly-diagnosed adult T-LBL patients (n=181) were divided into three groups: chemotherapy (no HSCT) group (89 patients), single auto-HSCT group (46 patients), and tandem auto-HSCT group (46 patients). The measurement of primary outcome was progression-free survival (PFS). The secondary outcomes were progression/relapse rate and overall survival (OS). Additionally, this study analyzed factors influencing toxicities related to tandem auto-HSCT treatment and patient prognosis. Results: The 3-year progression/relapse rate of the tandem auto-HSCT group was significantly lower than that of the single auto-HSCT group and chemotherapy group (26.5% vs 53.1% and 57.6%, p < 0.05). The 3-year PFS rate and OS rate of the tandem auto-HSCT group (73.5% and 76.3%, respectively) were significantly higher than those of the single auto-HSCT group (46.9% and 58.3%, respectively, p < 0.05) and the chemotherapy group (42.3% and 56.1%, respectively, p < 0.05). In the tandem auto-HSCT group, age and disease status after the first transplantation impacted the OS and PFS. Multivariate analysis identified disease status after the first transplantation as the only independent prognostic factor for outcome in T-LBL treated with tandem-HSCT. Conclusions: Tandem auto-HSCT improves long-term survival of adult T-LBL patients compared to recipients of chemotherapy alone or chemotherapy plus single auto-HSCT, and disease status after the first transplantation is an independent prognostic indicator for these patients. Funding Statement: This work was supported by grants from the National Natural Science Foundation of China (No.81370594, 81070388, 81270569, 81600166), the Scientific and Technological Innovation Program of Chongqing social undertakings and people's livelihood guarantee (cstc2016shms-ztzx10003), and Youth Innovation Project of Military Medicine of Chinese People’s Liberation Army (No.13QNP116). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: The study was performed in accordance with the Declaration of Helsinki and local laws. The protocol was approved by the ethic committee of each center, and written informed consent was obtained from all patients.

Tandem autologous hematopoietic stem cell transplantation for treatment of adult T-cell lymphoblastic lymphoma: a multiple center prospective study in China.

T-cell lymphoblastic lymphoma (T-LBL) is a highly aggressive form of lymphoma with poor clinical outcomes and no standard treatment regimen. In this study, we assessed the safety and efficacy of tandem autologous hematopoietic stem cell transplantation (auto-HSCT) for adult T-LBL and evaluated prognostic factors affecting survival. A total of 181 newly-diagnosed adult T-LBL patients were enrolled: 89 patients were treated with chemotherapy alone, 46 were allocated to the single auto-HSCT group, 46 were treated with tandem auto-HSCT. Median follow-up time was 37 months; the 3-year progression/relapse rate of the tandem auto- HSCT group was significantly lower than that of the single auto-HSCT and chemotherapy groups (26.5% vs. 53.1% and 54.8%). The 3-year progression- free survival (PFS) and overall survival (OS) rates of the tandem auto- HSCT group (73.5% and 76.3%) were significantly higher than those of the single auto-HSCT group (46.9% and 58.3%) and the chemotherapy group (45.1% and 57.1%). In the tandem auto-HSCT group, age and disease status after the first transplant impacted OS and PFS. Multivariate analysis identified that disease status after the first transplant was the only independent prognostic factor for patients treated with tandem-HSCT. In addition, diagnostic models of the initial CD8+CD28+/CD8+CD28– T-cell ratio in predicting the disease status were found to be significant. Taken together, tandem auto- HSCT can be considered an optimal strategy for adult T-LBL patients. (Study registered at: ChiCTR-ONN-16008480).

PS1093 IN ELDERLY PATIENTS WITH NEWLY DIAGNOSED DLBCL, CHANGE WEIGHT AFTER THE FIRST COURSE R-CHOP (-LIKE) CHEMOTHERAPY IS AN ADVERSE PROGNOSTIC FACTOR

Background: T-cell lymphoblastic lymphoma (T-LBL) is a highly aggressive form of lymphoma with poor clinical outcomes and lack of a standard treatment regimen. Aims: This study evaluated the safety and efficacy of tandem autologous hematopoietic stem cell transplantation (auto-HSCT) treatment for adult T-LBL and assessed factors affecting survival. Methods: Newly-diagnosed adult T-LBL patients (n = 160) were divided into three groups: chemotherapy (no HSCT) group (68 patients), single auto-HSCT group (46 patients), and tandem auto-HSCT group (46 patients). The measurement of primary outcome was progression-free survival (PFS). The intermediate outcomes were progression/relapse rate and overall survival (OS). Additionally, this study analyzed factors influencing toxicities related to tandem auto-HSCT treatment and patient prognosis. Results: The 3-year progression/relapse rate of the tandem auto-HSCT group was significantly lower than that of the single auto-HSCT group and chemotherapy group (19.6% vs 45.7% and 70.6%, p < 0.05). The 3-year PFS rate and OS rate of the tandem auto-HSCT group (68.3% and 72.5%, respectively) were significantly higher than those of the single auto-HSCT group (41.5% and 55.4%, respectively, p < 0.05) and the chemotherapy group (23.3% and 43.3%, respectively, p < 0.05). In the tandem auto-HSCT group, age and disease status after the first transplantation impacted the OS and PFS. Multivariate analysis identified disease status after the first transplantation as the only independent prognostic factor for outcome in T-LBL treated with tandem-HSCT. Summary/Conclusion: Tandem auto-HSCT improves long-term survival of adult T-LBL patients compared to recipients of chemotherapy alone or chemotherapy plus single auto-HSCT and disease status after the first transplantation is an independent prognostic indicator for these patients.

Tandem Autologous Hematopoietic Stem Cell Transplantation Treatment for Adult T-Cell Lymphoblastic Lymphoma: A Multiple Center Prospective Study in Southwestern China

BackgroudT-cell lymphoblastic lymphoma (T-LBL) is a highly aggressive lymphoma with very poor clinical outcomes which has not standard treatment. This study evaluated the efficacy and safety of tandem autologous hematopoietic stem cell transplantation (auto-HSCT) treatment for adult T-LBL and assessed the factors that affect survival.Methods160 newly diagnosed adult T-LBL patients were divided into three groups: chemotherapy group (68 patients), single auto-HSCT group (46 patients), and tandem auto-HSCT group (46 patients). The primary outcome measure was failure-free survival. The intermediate primary outcomes were progression/relapse rate and overall survival. Factors influencing toxicity related to tandem auto-HSCT treatment and prognosis for the patients were analyzed as well.ResultsThe 3-year progression/relapse rate of the tandem auto-HSCT group was significantly lower than that of the single auto-HSCT group and chemotherapy group (19.6% vs 45.7% and 70.6%, p < 0.05). The 3-year PFS rate and OS rate of the tandem auto-HSCT group (68.3% and 72.5%, respectively) were significantly higher than those of the single auto-HSCT group (41.5% and 55.4%, respectively, p < 0.05) and the chemotherapy group (23.3% and 43.3%, respectively, p < 0.05). In the tandem auto-HSCT group, age and disease status after the first transplant had an influence on the OS and PFS. Multivariate analysis identified disease status after the first transplant as the only independent prognostic factor for outcome in T-LBL.ConclusionsTandem auto-HSCT improves long-term survival of adult T-LBL patients. Disease status after the first transplant was an independent prognostic indicator for those patients. DisclosuresNo relevant conflicts of interest to declare.

High Dose Chemotherapy Followed by Tandem Autologous Hematopoietic Stem Cell Transplantation in Pediatric Patients with Malignant Brain Tumors: Single Institute

High Dose Chemotherapy Followed by Tandem Autologous Hematopoietic Stem Cell Transplantation in Pediatric Patients with Malignant Brain Tumors: Single Institute

Tandem Autologous Hematopoietic Cell Transplantation for Patients with Primary Progressive or Recurrent Hodgkin Lymphoma: A SWOG and Blood and Marrow Transplant Clinical Trials Network Phase II Trial (SWOG S0410/BMT CTN 0703)

Based on promising pilot data a phase II tandem autologous hematopoietic stem cell transplant (AHSCT) trial for relapsed/refractory Hodgkin lymphoma (HL) was performed in the US intergroup setting to determine if long-term progression-free survival (PFS) could be improved. Patients were enrolled after salvage therapy and stem cell collection. Sensitivity to salvage was defined by 1999 Standardized Response Criteria and did not include fluorodeoxyglucose-positron emission tomography. Cycle 1 consisted of melphalan 150 mg/m2 with half of the stem cells. For stable disease or better, patients received cycle 2 consisting of single doses of etoposide 60 mg/kg and cyclophosphamide 100 mg/kg and either total body radiation 12 Gy in 8 fractions over 4 days or BCNU 150 mg/m2/day for 3 days with the remaining stem cells. Of 98 enrolled patients, 89 were eligible and treated: 82 completed both cycles of AHSCT, 47 (53%) had primary refractory HL, and 72 (81%) were resistant to salvage therapy. There were no treatment-related deaths in the first year after AHSCT. With a median follow-up of 6.2 years (range, 2 to 7.7) for eligible patients who remained alive, the 2-year and 5-year PFS were 63% (95% CI, 52% to 72%) and 55% (95% CI, 44% to 64%) respectively; the 2-year and 5-year overall survival were 91% (95% CI, 83% to 95%) and 84% (95% CI, 74% to 90%), respectively. Univariate Cox regression analysis showed Zubrod performance status and lactate dehydrogenase levels > 1 times upper limit of normal at the time of enrollment were significantly associated with PFS. The observed 5-year PFS of 55% suggests the tandem approach appears to be effective in treating HL patients demonstrated to have poor prognosis in prior single AHSCT trials. This trial was registered at www.clinicaltrials.gov as NCT00233987.

Guillain-Barre Syndrome Associated with Rapid Immune Reconstitution Following a Tandem Autologous Hematopoietic Stem Cell Transplantation. Study of a Case and Review of the Literature

Introduction: Guillain-Barre syndrome (GBS) is a frequent cause of neuromuscular paralysis and usually occurs after an immunoallergic reaction, most often after respiratory or gastrointestinal infection. However, rare cases of Guillain-Barre syndrome are described, associated with hematopoietic stem cell transplantation. Observation: Patient n° 20452690. The authors report the case of 21 years old man, treated for Hodgkin lymphoma with a recurrence at 18 months, who enjoyed second autologous hematopoietic stem cell transplantation after conditioning chemotherapy, then developed a Guillain-Barre syndrome. Plasma exchanges were made before a neurological worsening. Thereafter, five cycles of intravenous immunoglobulin were performed monthly. Unfortunately this development was hampered by mechanical respiratory complication that led to the death of the patient, the 237th day of evolution. The final diagnosis of Guillain-Barre syndrome, occurred in a context of post-transplant immune reconstitution in a patient treated for Hodgkin lymphoma was retained. Discussion: GBS is a rare complication of hematopoietic stem cell transplantation. After literature review, we collected 33 cases related to this disease, 10 occurred after autograft. Etiopathogenic mechanisms remain obscure. Despite the use of immunomodulatory treatment, the prognosis is often severe and dark. Conclusion: GBS is possible after autologous hematopoietic stem cell transplantation indicated for the treatment of Hodgkin lymphoma. The initial clinical severity, despite safeguards and use of immunomodulatory therapy, will cause often deleterious and poor outcome. To our knowledge, this well documented observation is the first case indicated for Hodgkin lymphoma.

Evolving strategies with immunomodulating drugs and tandem autologous/allogeneic hematopoietic stem cell transplantation in first line high risk multiple myeloma patients

We prospectively evaluated in high-risk myeloma patients the efficacy and toxicity of tandem autologous hematopoietic stem cell transplantation (auto-HSCT) followed by reduced-intensity conditioning (RIC) and allogeneic (allo)-HSCT with bortezomib and donor lymphocyte infusions introduction after allo-HSCT (group 1). Results were compared with results from tandem auto-RIC-allo-HSCT without bortezomib (group 2). Groups 1 and 2 were compared to matched patients not receiving allo-HSCT from the Intergroupe Francophone du Myélome prospective studies. Allo-HSCT groups included 25 patients (12 in group 1, 13 in group 2). All patients engrafted. There were 8 acute GVHD (7 grade II [3 in group 1], 1 grade III in group 1)] and 11 chronic GVHD (3 limited [in group 1], 8 extensive [1 in group 1]). Matched population included 36 controls for group 1 and 39 for group 2. After a median follow-up of 55 months (range, 3-142 months), median overall survival was not reached in group 1 versus 65 months (51-not reached [NR]) in its matched group (p = 0.027); it was 96 months (49-NR) in group 2 versus 91 months (32-NR) in its matched group (p = 0.77). Median progression-free survival was 49 months (29-NR) in group 1 and was 25 months (range, 21-35 months) in its matched group (p = 0.0045); it was 31 months (22-NR) in group 2 and 28 months (range, 21-40 months) in its matched group (p = 0.0776). Tandem auto-RIC-allo-HSCT including new molecules and immunomodulation after transplantation could be used as a first-line treatment for high-risk myeloma patients.

Long term follow-up report of cardiac toxicity in patients with multiple myeloma treated with tandem autologous hematopoietic stem cell transplantation

BackgroundTandem autologous hematopoietic stem cell transplantation (ta-HSCT) is a standard treatment for multiple myeloma (MM). Patients receive a high-dose cyclophosphamide (CY), followed by two myeloablative cycles of melphalan (MEL). There are scarce data about long term cardiotoxicity.Patients and methods.We studied 12 patients (62.25 ± 8.55 years) six years after the completion of MM treatment with ta-HCST. Late cardiotoxic effects were evaluated clinically and echocardiographically.ResultsNone of the patients developed clinical signs of heart failure, all were in sinus rhythm and NT-pro BNP concentration was elevated (778 ± 902.76 pg/mL). The left ventricular (LV) size remained normal. The LV ejection fraction did not decrease (73.75 ± 5.67%, 69.27 ± 6.13%, p = NS). The LV diastolic function parameters (E, A, ratio E/A and A/a) did not change significantly. In tissue Doppler parameters we observed a nonsignificant decrease in Em (10.26 ± 2.63 cm/s, 7.57 ± 1.43 cm/s) and Sm velocities (8.7 ± 0.87 cm/s, 7.14 ± 1.17 cm/s, p = NS). The E/Em values were in an abnormal range (8.66 ± 1.05, 10.55 ± 2.03).ConclusionsThe treatment of MM with ta-HSCT, during which patients receive a high dose CY followed by two myeloablative cycles of MEL, causes mild, chronic, partially reversible and clinically silent cardiotoxic side-effects. However, ta-HSCT in patients with MM is a safe regarding cardiotoxic side effects, but, because of increasing life expectancy needs long term attention.

Tandem Autologous Hematopoietic Stem Cell Transplants (AuHCT) with or without Maintenance Therapy (auto-auto) Versus Single AuHCT Followed by HLA Matched Sibling Non- Myeloablative Allogeneic HCT (auto-allo) for Patients with Standard Risk (SR) Multiple Myeloma (MM): Results From the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0102 Trial

AbstractAbstract 41AuHCT improves survival in patients with MM, but disease relapse and progression remain a challenge. Both tandem AuHCT and post transplant maintenance therapy improve progression-free survival (PFS). Alternatively, allogeneic HCT has the potential to reduce disease progression through a graft-versus-myeloma effect. Use of nonmyeloablative conditioning regimens allows the latter approach to be used with reduced treatment-related mortality (TRM). BMT CTN 0102 was a multicenter phase III trial that biologically assigned patients with MM to auto-auto using melphalan 200mg/m2 (MEL 200) conditioning or an auto-allo approach using MEL 200 followed by alloHCT with 2 Gy total body irradiation. Graft-versus-disease (GVHD) prophylaxis was cyclosporine and mycophenolate mofetil. The primary endpoint was 3-year progression free survival (PFS). Between December 2003 and March 2007, 710 patients from 43 US centers were enrolled. Patients were assigned to the auto-allo arm based on availability of an HLA-matched sibling donor at time of enrollment. Patients in the auto-auto arm were further randomized to thalidomide and dexamethasone (Thal-Dex) for 1 year or observation (obs). Among 625 patients with SR MM (absence of chromosome 13 deletion by metaphase karyotyping and β-2 microglobulin ≤ 4mg/L), 436 were assigned to auto-auto (217 Thal-Dex, 219 obs) and 189 to auto-allo. Compliance with Thal-Dex was poor, with 84% of patients not completing prescribed therapy. PFS and overall survival (OS) between the Thal-Dex and obs cohorts were equal and these arms were pooled for the primary analysis. The auto-auto and auto-allo groups differed in age (median 55y vs. 52y, p =0.01) and time between first and second transplants (median 98d vs 105d, p =0.02), but were otherwise balanced. Complete and near complete (CR+nCR) response rates at study entry were 24% for both groups. Three-year PFS was 46% and 43% (p=0.67) and 3-year OS was 80% and 77 % (p=0.19) for the auto-auto and auto-allo groups, respectively. Corresponding probabilities for 3-year progression/relapse were 50% and 46% (p=0.8) and for 3-year TRM were 4% and 11% (p=0.04). Among auto-allo patients, probabilities of grade III-IV acute and chronic GVHD were 9% and 47%, respectively. Eighty-two percent of patients in each arm received the assigned second transplant. Among 522 patients who received their second transplant, 3-year PFS was 47% and 44% (p=0.89) with auto-auto and auto-allo, respectively. Disease response rates at day 56 after second HCT were: 50% very good partial response (VGPR) or better and 40% CR+nCR in the auto-auto group; and 49% (VGPR or better, p=0.8) and 48% (CR+nCR,p=0.12) in the auto-allo group. In conclusion, there were no differences in 3-year PFS and OS between patients receiving auto-auto or auto-allo. Potential benefits of graft-versus-myeloma to reduce disease progression or relapse were offset by increased TRM. Thal-Dex maintenance did not improve PFS or OS, likely due to poor tolerability of this regimen. At 3 years, the auto-allo approach for SR MM had no added benefit compared to tandem AuHCT. [Display omitted] Disclosures:Krishnan:Celgene: Speakers Bureau. Stadtmauer:Celgene: Speakers Bureau. Comenzo:Millenium Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Elan Pharmaceuticals: Consultancy; Genzyme: Research Funding; Celgene: Research Funding; Ortho: Research Funding. Hari:Celgene: Research Funding. Qazilbash:Celgene: Speakers Bureau. Vesole:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Giralt:Celgene: Honoraria, Speakers Bureau; Millenium: Honoraria, Speakers Bureau.

Cardiac toxicity of high-dose cyclophosphamide and melphalan in patients with multiple myeloma treated with tandem autologous hematopoietic stem cell transplantation

Tandem autologous hematopoetic stem cell transplantation (HSCT) is an effective treatment in patients with multiple myeloma (MM). Patients receive high-dose cyclophosphamide (CY) followed by two myeloablative dosages of melphalan (MEL). Cardiotoxicity treatment related data are scanty. In 30 patients with MM chemotherapy was followed by high-dose CY (cycle CY), and two autologous tandem HSCT treatments with MEL (cycles MEL I and MEL II). During each 15-day treatment troponin I (TnI), brain natriuretic peptide (BNP) and endothelin-1 (ET-1) were controlled at six time points. All patients underwent conventional and tissue Doppler echocardiography prior to CY therapy (Eho 0), before cycle MEL I (Eho 1), before cycle MEL II (Eho 2), and 3 months after the completion of therapy (Eho 3). None of the patients developed clinical signs of heart failure. The peak TnI concentrations were noted at days 8, 11, and 15 during all three chemotherapy cycles. During all three cycles there was a significant increase in baseline BNP concentrations and BNP levels measured at day 1 after treatment with CY and MEL (CY: P = 0.0001, MEL I: P = 0.001, MEL II: P = 0.001). The highest BNP concentration occurred during CY treatment (0.517 +/- 0.391 microg/L). During cycles MEL I and MEL II we noted the peak BNP concentrations at day 4 following chemotherapy (MEL I 0.376 +/- 0.418 microg/L; MEL II 0.363 +/- 0.379 microg/L). During all three cycles the highest ET-1 levels occurred at day 1 after chemotherapy (CY 1.146 +/- 1.313 ng/L; MEL I 1.054 +/- 2.242 ng/L; MEL II 0.618 +/- 0.539 ng/L). A significant increase in ET-1 concentrations relative to the basal values occurred only in cycle MEL II (P = 0.003). The duration of wave a in the Doppler pulmonary vein flow increased significantly (Eho 0/Eho 1: P = 0.008, Eho 0/Eho 3: P = 0.026). There was a significant decrease in the A/a ratio in flow velocities during chemotherapy (Eho 0/Eho 1: P = 0.002, Eho 0/Eho 3: P < 0.0001). Early diastolic tissue Doppler velocities (Em) decreased significantly during individual cycles of chemotherapy (P = 0.006). A significant post-treatment increase in the incidence of mitral regurgitation was observed (Eho 0/Eho 3: P = 0.003). Treatment of MM patients with tandem autologous HSCT is cardiotoxic. Our patients did not develop clinically overt heart failure or myocardial necrosis. Increased plasma levels of BNP and ET-1 were compatible with transient neurohormonal activation of heart failure. Doppler echocardiography studies revealed worsening of left ventricular diastolic function and occurrence of functional mitral regurgitation.