Secondary poor graft function after autologous stem cell transplantation in multiple myeloma: a case-based expert review and successful rescue with secondary autologous stem cell infusion

Autologous Hematopoietic Stem Cell Transplantation May Reverse Renal Failure in Patients with Multiple Myeloma

Kinetics of Myeloid-Derived Suppressor Cells during Stem Cell Mobilization and Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma and Lymphoma Patients

Final Report of Safety and Efficacy From a Novel Conditioning Regimen, Individualized Once-Daily Intravenous Busulfan with Bortezomib, in Relapsed Multiple Myeloma Patients Undergoing a Second Autologous Hematopoietic Stem Cell Transplantation.

Depth of Response and Outcomes in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation

Background:Autologous hematopoietic stem cell transplantation is the main treatment for lymphoma. While relapse after autologous hematopoietic stem cell transplantation (ASCT) is still challenging for high‐risk aggressive lymphoma.Aims:This study was to investigate the efficacy and safety of maintenance therapy post‐ASCT.Methods:From June 2009 to December 2018, patients with high‐risk aggressive lymphoma in our hospital were treated with maintenance therapy post‐ASCT according to the patient's needs and wishes, and then assigned to maintenance group or observation group. The end point of follow‐up was disease progression or death. The 4‐year overall survival (OS) and disease‐free survival (DFS) were compared between these two groups.Results:A total of 92 patients were enrolled, apart from 2 cases of early death, the remaining 90 patients underwent ASCTsuccessfully and achieved CR post‐ASCT. 59 patients were assigned to the observation group, and 31 patients to the maintenance group, including 22 with rituximab regimen,7 with DPP/DCEP‐G alternation regimen, and 2 with Chidamideregimen. There were no significant differences in gender, age,diagnosis,IPI score,pre‐transplant disease status, and hematopoietic reconstitution between the two groups. The main causes of death were disease recurrence. No serious adverse reactions occurred during the maintenance treatment period. After a median follow‐up of 616 days (12‐2854 days), and the DFS of the 1st, 2nd,3rd and 4thyears were67.1% VS 95.2%, 51.1% VS 90.5%, 48.1% VS 90.5%, 43.8% VS 90.5% (P = 0.002), respectively. The OS of the 1st, 2nd, 3rd and 4thyears were 90.0% VS 100%, 84.4% VS 95.2%, 77.3% VS 95.2%, 73.3% VS 95.2% (P = 0.126), respectively.For the overall survival rate, single factor analysis showed age <30 years old, LDH increased before ASCTwere prognostic factors affecting OS; COX multi‐factor regression analysis showed age <30 years old, LDH increased before ASCTwere independent prognostic factors for OS. The risk of death in patients <30 years of age was 4.376 times higher than that in patients aged 30 years or older (P = 0.026, HR = 4.376, 95% CI = 1.188‐16.116). The risk of death in patients with LDH increased before ASCT was 5.165 times higher than in patients with normal LDH before ASCT (P = 0.015, HR = 5.165, 95% CI = 1.375‐19.395).For the disease‐free survival rate, single factor analysis showed that the initial admission to LDH increased, LDH increased before ASCT, IPI score≥2 points, maintenance treatment after ASCT were prognostic factors for DFS; COX multi‐factorregression Analysis showed that LDH increased before ASCTand maintenance treatment after ASCT were independent prognostic factors for DFS. The risk of recurrence of patients with LDH increased before ASCT was 2.648 times higher than that of normal LDH patients before ASCT (P = 0.034, HR = 2.648, 95% CI = 1.078‐6.507), and the risk of recurrence in maintenance‐treated patients after ASCT was 0.130 times than that in patients without maintenance therapy after ASCT (P = 0.006, HR = 0.130, 95% CI = 0.031‐0.557).Conclusion: Maintenance therapy post‐ASCT could reduce the risk of relapse and promote disease‐free survival, which deserves further investigation.Summary/Conclusion:Maintenance therapy post‐ASCT could reduce the risk of relapse and promote disease‐free survival, which deserves further investigation.image

A Prospective, Randomized Trial Examining the Use of G-CSF Versus No G-CSF in Patients Post-Autologous Transplantation

6552 Background: Plerixafor for mobilization of autologous stem cells (ASC) has increased the yield of transplanted ASC and is evolving as an important option for mobilization. A prior study reported a 10% incidence of SN after AHSCT (BMT 2009 Aug; 44(3): 175-83). Incidence and outcome of SN in the setting of Plerixafor/G-CSF (P/G), is unknown. We report the incidence and possible etiology for the development of SN in pts undergoing AHSCT for lymphoma at our institution. Methods: Data from 80 consecutive AHSCT pts over a 2 year period were reviewed. All pts were mobilized using P/G. Demographics, AHSCT indication, prior therapies (Rx), conditioning regimen (CR), engraftment and post-transplant complications were identified and collected. SN was defined as ANC <1000 after initial engraftment. Results: 80 pts underwent an AHSCT for lymphoma from 2009-11. 70 pts had evaluable data. 37 (52.86%) pts (average age 55.4 yrs) were male and 33 (47.14%) pts (average age 48.3 yrs) female. 25 (35.7%) pts had ≥2 comorbidities. Indications included relapsed/ refractory B-NHL, T-NHL and HL. 47 (67%) pts had Stage IV ds, 48.9% with BM involvement. 17 (24.3%) pts had >2 Rx, 18 (25.7%) with loco-regional XRT and 3 (4.3%) with RIT. CR included BEAM, BEC and Benda-EAM +/- Rituxan. # of CD34+ cells given ranged; 1.77-19.99 x 10^6/kg. Neutrophil engraftment occurred at a median of 11 days. 26 (37.14%) pts developed SN possibly from PCP prophylactic antibiotics and infections. Prior BM involvement, Rx or XRT had no role. 5 (45.4%) pts with Benda-EAM CR had SN. Associated morbidity/mortality were not noted. Conclusions: We conclude that secondary neutropenia is common after autologous stem cell transplant using the Plerixafor/GCSF combination for mobilization and is higher than reported in the literature (37% vs 10%). Patients who received this combination for mobilization should be followed up closely in the post-transplant period for secondary neutropenia. About half the patients who received the Benda-EAM conditioning regimen developed secondary neutropenia warranting its use with caution outside of a clinical trial.

The aim was to assess the cognitive dysfunction and physical disability after autologous hematopoietic stem cell transplantation (AHSCT), to explore the potential factors influencing disability regression after AHSCT and to estimate the safety of low-dose immunosuppressive therapy in highly active Multiple Sclerosis (MS) patients. In single-center prospective study patients who failed to conventional therapies for highly active relapsing MS underwent the AHSCT. The disability was followed up with Expanded Disability Status Scale and cognition with Brief International Cognitive Assessment for Multiple Sclerosis. Twenty four patients [18 (72.0%) female] underwent AHSCT. Two patients of 13 had one relapse during the first year and three patients—during the second year after AHSCT. Disability regression was found in 84.6% of patients. The scores of information processing speed and verbal learning were significantly higher at month 12 after AHSCT. The clinical variable that explained the disability regression at months 6 and 12 after AHSCT was the disability progression over 6 months before AHSCT. No transplant related-deaths were observed. Selective cognitive improvement was found after AHSCT in MS patients. The disability may be temporarily reversible after AHSCT in a significant proportion of highly active RMS patients if AHSCT is well-timed performed.

Objective: To investigate the clinical prognostic value of dynamic minimal residual disease (MRD) after autologous hematopoietic stem cell transplantation (AHSCT) in patients with multiple myeloma (MM). Methods: Patients with MM who underwent AHSCT in Beijing Chao-Yang Hospital from February 2016 to December 2019 were enrolled in this study. All the patients in the study had complete baseline data at the diagnosis. AHSCT was performed after induction chemotherapy. Response evaluation was performed after induction therapy. All the patients were assessed at approximately 100 days after AHSCT. Bone marrow MRD by NGF was performed every three months and dynamically monitored for at least 12 months. All the patients were divided into different groups according to cytogenetics and MRD status. Survivals in different groups were analyzed by IBM SPSS 22.0 statistical software. Results: A total of 150 patients with MM were enrolled in this study at last, including 66 patients in the cytogenetic standard risk group and 84 patients in the cytogenetic high-risk group. The median age was 54 years (range 30-68 years) and 87 male patients (58.0%) was in the study. The median follow-up was 36 months (range 16-72 months). Patients in the standard-risk group had better clinical prognosis than those in the high-risk group [median PFS in the standard-risk group was not achieved, and median PFS in the high-risk group was 45 months (P<0.001); median OS of both groups was not reached, and the estimated 3-year OS rate of the standard-risk group and the high-risk group was 95.2% and 78.9%, respectively (P=0.001)]. According to MRD status of patients, patients in each group were divided into three subgroups: persistent positive (Ppos), transient negative (Tneg) and persistent negative (Pneg). The median OS and median PFS of all subgroups in the standard-risk group was not reached (P=0.324 and P=0.086). In high-risk group, the median OS of MRD Pneg subgroup was not reached, and the estimated 3-year OS rate was 100%; The median OS of MRD Ppos subgroup was 52 months, and MRD Tneg subgroup only 31 months (P=0.002); the median PFS of MRD Pneg group was not reached, and the estimated 3-year PFS rate was 85.4%; median PFS of MRD Ppos subgroup was 40 months, and MRD Tneg subgroup only 17 months (P=0.001). Conclusions: MRD Pneg might overcome the adverse prognosis of MM patients with high-risk cytogenetics. However, MRD Tneg might be a poor prognostic factor for the patients with cytogenetic high-risk MM.

The purposes of this study were to evaluate the infection by hepatitis B virus (HBV) and its impact on survival and to provide a clinical reference for monitoring and treating HBV during and after autologous hematopoietic stem cell transplantation (ASCT) in patients with multiple myeloma (MM). A retrospective analysis of HBV infections was performed in 70 MM patients who received a sequential bortezomib-containing induction therapy and ASCT in our department from June 2006 to February 2012. Among the 70 patients in our study, 11 cases (15.7 %) were hepatitis B surface antigen positive (HBsAg+), and 23 cases (33.3 %) were hepatitis B core antibody positive (HBcAb+). Eight cases were HBsAg, hepatitis B e antibody (HBeAb), and HBcAb positive, while one case was HBsAg, hepatitis B e antigen (HBeAg), and HBcAb positive. The median follow-up times for the HBsAg+ group and the HBsAg-negative (HBsAg-) group were 27.0 (7.6-85.2) months and 28.7 (7.1-111.0) months, respectively. The 1-year, 2-year, and 3-year overall survival rates of the HBsAg+ group were 90.9, 80.8, and 34.6 %, respectively, and the median survival time was 31.2 months (95 % CI, 24.8-37.6). The 1-year, 2-year, and 3-year overall survival rates of the HBsAg- group were 98.2, 94, and 84.6 %, respectively, while the median survival time was not yet available. There was a statistically significant difference (p=0.008) in the overall survival rate between the two groups. By Cox regression analysis, we found that the HBsAg+ status was a prognostic factor, which could independently influence the overall survival rate for ASCT. In conclusion, the HBsAg+ status is an independent risk factor for patients with MM receiving ASCT. The application of standard antiviral treatment might help to overcome this risk factor.

CAC-MM-001: A B-Cell Maturation Antigen (BCMA)-Directed Chimeric Antigen Receptor T-Cell (CAR-T) Therapy Followed By Autologous Stem Cell Transplantation and Second CAR-T (CART-ASCT-CART2) in Newly Diagnosed Multiple Myeloma Patients with P53 Gene Abnormalities

Engraftment Syndrome After Hematopoietic Stem Cell Transplantation in Multiple Myeloma

To evaluate the effect of recombinant human interleukin 11 (rhIL-11) on hematological recovery after autologous hematopoietic stem cell transplantation (AHSCT) in patients with lymphoma. A retrospective study was carried out on 73 patients with lymphoma after AHSCT. The patients were divided into two groups. The study group (n = 35) received rhIL-11 1.5 mg daily from the fifth day after AHSCT to the day when platelets recovering to 80.0×10⁹/L. The control group (n = 38) did not receive rhIL-11 after AHSCT. All the 73 patients finished AHSCT from Mar 2003 to Dec 2008 in our department. Thirty-five patients received rhIL-11 and 38 patients did not. In the rhIL-11 group and control group, the nadir of platelet was (18.9 ± 5.0)×10⁹/L and (21.5 ± 6.0)×10⁹/L, respectively, with a significant difference (P = 0.04). The median time of platelet recovering to 50.0×10⁹/L was (14.3 ± 5.5) d and (13.2 ± 4.5) d (P = 0.37) in the two groups. There was no significant difference (P = 0.82) in the median numbers of platelet transfusion in the two groups. The curves of the mean of daily absolute platelet counts of the two groups were similar (P = 0.22). Adverse events related to rhIL-11 were not found in the rhIL-11 group. The results of this study do not show obviously accelerating effect of rhIL-11 on the platelet recovery in lymphoma patients after AHSCT and obvious increase of adverse events after rhIL-11 administration.

Phase III Intergroup Study of Lenalidomide (CC-5013) Versus Placebo Maintenance Therapy Following Single Autologous Stem Cell Transplant for Multiple Myeloma (CALGB 100104): Initial Report of Patient Accrual and Adverse Events.

The Prognostic Value of Dynamic Minimal Residual Disease after Autologous Hematopoietic Stem Cell Transplantation in Patients with Multiple Myeloma in Novel-Agent Era: Long-Term Follow-up