Pre-transplant Chemotherapy Research Articles

A single-center retrospective study of salvage allogeneic hematopoietic stem cell transplantation pretreated with MeCBA regimen for refractory/relapsed acute myeloid leukemia

Thirty refractory relapsed acute myeloid leukemia (R/R AML) patients who received salvage allo-HSCT with MeCBA conditioning regimen from January 2018 to June 2022 at Henan Cancer Hospital were included, and their clinical data were reviewed. There were 16 males and 14 females among the 30 patients with a median age of 37 (16-53) years. There were 3 sibling allograft donor transplants, 1 unrelated donor transplant, and 26 haplotype transplants. The median course of pre-transplant chemotherapy was 4 (3-22). The time of neutrophil engraftment was 14 (9-22) days and 18 (10-40) days for platelet. The 30-day cumulative incidence of neutrophil engraftment was 100% and the 100-day cumulative incidence of platelet engraftment was 96.7% (95% CI 85.4% -97.5% ). 22 (73.3% ) patients experienced grade 1-2 gastrointestinal reactions, and there was no grade 3-4 organ toxicity. With a median follow-up of 37.1 months, the overall survival (OS) rate, event-free survival (EFS) rate, cumulative recurrence rate (CIR), and non-recurrence mortality (NRM) rate at 3 years after transplantation were 70.0% (95% CI 50.3% -83.1% ), 65.3% (95% CI 44.8% -79.8% ), 21.2% (95% CI 9.2% -44.4% ) and 16.7% (95% CI 7.3% -35.5% ), respectively.

Evaluation of the bone marrow transplantat recipient patients regarding fever onset, fever permanence, risk factors, and underlying causes, during the pre-engraftment phase

Background: Patients undergoing bone marrow transplantation (BMT) are at higher risk of immune system deficiency. The immunosuppression, followed by pre-transplant chemotherapy makes patients vulnerable to a variety of infections, and fever is one of the first symptoms, which could develop as a result of infectious or non-infectious diseases. In the present study, the features of the fever during the pre-engraftment stage in BMT-receiving patients have been investigated.
 Materials and Methods: Sixty-four patients receiving BMT were prospectively evaluated during the pre-engraftment phase to evaluate the evidence of the febrile reaction. Data concerning the cause of fever, microbiological tests, the treatments and fever onset pattern, and treatment outcomes were recorded and analyzed.
 Results: 73.4% of the patients had autologous transplants, and the others received allogeneic. After transplantation, 75% of patients encountered fever during the pre-engraftment period. Of the 48 patients, 47.9% of the patients suffered from fever of unknown origin (FUO). Age, gender, underlying malignancy, type of transplantation, and acute phase reactants levels before transplantation were not associated with fever development. Among febrile patients, patients with autologous transplantation were significantly more likely to develop FUO (p-value = 0.036) There was also no significant difference in the onset of fever between patients with infectious fever and who suffered FUO
 Conclusions: During BMT, half of the patients developed a fever of unknown origin; nevertheless, it seems that patients undergoing autologous transplantation are at higher risk of FUO compared to patients who received an allogeneic transplant.

Sorafenib plus intensive chemotherapy in newly diagnosed FLT3-ITD AML: a randomized, placebo-controlled study by the ALLG

AbstractSorafenib maintenance improves outcomes after hematopoietic cell transplant (HCT) for patients with FMS-like tyrosine kinase 3–internal tandem duplication (FLT3-ITD) acute myeloid leukemia (AML). Although promising outcomes have been reported for sorafenib plus intensive chemotherapy, randomized data are limited. This placebo-controlled, phase 2 study (ACTRN12611001112954) randomized 102 patients (aged 18-65 years) 2:1 to sorafenib vs placebo (days 4-10) combined with intensive induction: idarubicin 12 mg/m2 on days 1 to 3 plus either cytarabine 1.5 g/m2 twice daily on days 1, 3, 5, and 7 (18-55 years) or 100 mg/m2 on days 1 to 7 (56-65 years), followed by consolidation and maintenance therapy for 12 months (post-HCT excluded) in newly diagnosed patients with FLT3-ITD AML. Four patients were excluded in a modified intention-to-treat final analysis (3 not commencing therapy and 1 was FLT3-ITD negative). Rates of complete remission (CR)/CR with incomplete hematologic recovery were high in both arms (sorafenib, 78%/9%; placebo, 70%/24%). With 49.1-months median follow-up, the primary end point of event-free survival (EFS) was not improved by sorafenib (2-year EFS 47.9% vs 45.4%; hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.51-1.51; P = .61). Two-year overall survival (OS) was 67% in the sorafenib arm and 58% in the placebo arm (HR, 0.76; 95% CI, 0.42-1.39). For patients who received HCT in first remission, the 2-year OS rates were 84% and 67% in the sorafenib and placebo arms, respectively (HR, 0.45; 95% CI, 0.18-1.12; P = .08). In exploratory analyses, FLT3-ITD measurable residual disease (MRD) negative status (<0.001%) after induction was associated with improved 2-year OS (83% vs 60%; HR, 0.4; 95% CI, 0.17-0.93; P = .028). In conclusion, routine use of pretransplant sorafenib plus chemotherapy in unselected patients with FLT3-ITD AML is not supported by this study.

Lenalidomide maintenance following high-dose therapy and autologous haematopoietic stem cell transplantation in chemo-resistant or high-risk non-Hodgkin lymphoma: A phase I/II study.

Improved maintenance treatments are needed for patients with relapsed/refractory aggressive lymphomas after autologous haematopoietic stem cell transplantation (ASCT). Several studies with lenalidomide have been found to have activity in the treatment of relapsed/refractory aggressive lymphomas. In the present phase I/II, single-arm, open-label study, 59 patients with high-risk relapsed non-Hodgkin lymphoma received pretransplant BEAM chemotherapy and ASCT followed by 12 months of maintenance lenalidomide once daily on Days 1-21 (28-day cycles) beginning at post-transplantation Day 100. The most common histologies were mantle cell lymphoma (56%) and diffuse large B-cell lymphoma (24%). The maximum tolerated dose in the dose-finding part of the study was 15 mg, but cytopenias led to the subsequent adoption of a 10 mg dose in the final study. Sixteen patients (27%) completed 12 cycles of lenalidomide maintenance. The most common reason for discontinuation was adverse events (31%). These were primarily haematologic, and 56% of patients experienced Grade 3-4 events. Two-year PFS rates (95% CIs) were 70% (56%-80%), 45% (19%-68%) and 81% (66%-90%); 2-year OS rates (95% CIs) were 91% (80%-96%), 93% (61%-99%) and 90% (76%-96%) in all patients, patients completing and patients not completing 12-month maintenance respectively. These results do not support the use of lenalidomide maintenance in this setting.

Primary Cancer Matters in Therapy-related Myeloid Neoplasm Patients Receiving Allogeneic Hematopoietic Cell Transplantation: A Study From the Chronic Malignancies Working Party of the EBMT

Primary Cancer Matters in Therapy-related Myeloid Neoplasm Patients Receiving Allogeneic Hematopoietic Cell Transplantation: A Study From the Chronic Malignancies Working Party of the EBMT

Intravenous Busulfan, Dimethylacetamide and neurotoxicity after high-dose pretransplant conditioning chemotherapy.

Intravenous Busulfan, Dimethylacetamide and neurotoxicity after high-dose pretransplant conditioning chemotherapy.

More than two courses of pre-transplant consolidation therapy benefits patients with acute myeloid leukemia in the first complete remission who underwent human leukocyte antigen-matched sibling allografts: a multicenter study.

Although the need for consolidation chemotherapy after successful induction therapy is well established in patients with acute myeloid leukemia (AML) in first complete remission (CR1), the value of consolidation chemotherapy before allogeneic hematopoietic stem cell transplantation remains controversial. We retrospectively compared the effect of the number of pre-transplant consolidation chemotherapies on outcomes of human leukocyte antigen-matched sibling stem cell transplantation (MSDT) for patients with AML in CR1 in multicenters across China. In our study, we analyzed data of 373 AML patients in CR1 from three centers across China. With a median follow-up of 969 days, patients with ≥ 3 courses of consolidation chemotherapy had higher probabilities of leukemia-free survival (LFS) (85.6% vs . 67.0%, P < 0.001) and overall survival (89.2% vs . 78.5%, P = 0.007), and better cumulative incidences of relapse (10.5% vs . 19.6%, P = 0.020) and non-relapse mortality (4.2% vs . 14.9%, P = 0.001) than those with ≤ 2 courses of consolidation chemotherapy. Pre-transplantation minimal residual disease-negative patients with AML in CR1 who received MSDT with ≥ 3 courses of consolidation chemotherapy had a higher probability of LFS (85.9% vs . 67.7%, P = 0.003) and a lower cumulative incidence of relapse (9.6% vs . 23.3%, P = 0.013) than those with ≤ 2 courses. Our results indicate that patients with AML in CR1 who received MSDT might benefit from pre-transplant consolidation chemotherapy.

Lack of complete response pretransplant is not associated with inferior overall survival for stage 4a metastatic retinoblastoma.

Stage 4a metastatic retinoblastoma (RB) is curable with intensive multimodality therapy including myeloablative chemotherapy with autologous stem cell transplant (HDC-ASCT) and involved field radiation therapy (IFRT). To our knowledge, no data exist on the impact of (a) pre-ASCT disease status, and (b) IFRT to sites of metastatic disease post ASCT on survival. We retrospectively reviewed patients with stage 4a metastatic RB who underwent induction chemotherapy followed by HDC-ASCT, with or without IFRT, to residual tumor sites at Memorial Sloan Kettering Cancer Center (MSKCC) (n=24). The degree of postinduction response prior to ASCT did not affect outcome, with 5-year overall survival (OS) of 68% and 86% in patients who achieved complete response (CR) and very good partial response (VGPR)/partial response (PR) prior to ASCT, respectively. IFRT administered post ASCT in patients with possible residual bony metastatic disease increases the likelihood of developing osteosarcoma in the radiation field. OS for patients with stage 4a metastatic RB treated with ASCT with VGPR or PR to pretransplant chemotherapy was not significantly different from patients with CR. In addition, IFRT does not seem to be required for bony disease control and increased the likelihood of developing osteosarcoma.

Long-Term Clinical Outcomes of Severe Combined Immunodeficiency Patients Given Nonablative Marrow Transplants

Severe combined immunodeficiency (SCID) is a syndrome characterized by profound T-cell deficiency that is universally fatal in infancy unless immune reconstitution isachieved by hematopoietic stem cell transplantation, gene therapy, or enzyme replacement. Published long-term clinical follow-up is limited for transplanted patients with SCID. To characterize the long-term outcomes of patients with SCID treated at a single center. We examined the clinical outcomes of 177 successive SCID infants given allogeneic bone marrow over 38 years without pretransplant chemotherapy or post-transplant graft-versus-host disease prophylaxis. A total of 90% received T-cell-depleted haploidentical parental marrow. Clinical status was assessed by questionnaires delivered by mail or electronically. Molecular type of SCID, demographics, and type, date and age of transplant were obtained from a database. Eighty-eight questionnaires were completed for survivors ranging in age from 2 to 38 years. Survival remained higher in those transplanted before 3.5 months of age. Half of the cohort remained on immunoglobulin replacement. Health conditions reported included rashes, anxiety, depression, warts, and mouth ulcers. Most reported that these were transient, self-resolving issues. Attention-deficit/hyperactivity disorder, warts, and learning disabilities were reportedly more prevalent than in the general population. Most reported having no active concerns about their health. We found substantial scholastic achievement, with half of adult patients reporting college attendance. Most patients had a healthy body mass index. Overall, our findings are consistent with those in the last update in 2009 in this population. Age at transplant remains a key variable in survival.

Blast Phase Myeloproliferative Neoplasm: A Mayo Agimm Study of 419 Consecutive Cases

Background:JAK2 mutation-enriched myeloproliferative neoplasms (MPN) might progress into blast phase disease (MPN-BP), operationally defined by the presence of ≥20% blasts in the peripheral blood (PB) or bone marrow (BM) (Blood 2016;127:2391). In the current study, we reviewed consecutive cases of MPN-BP from the institutional databases of the Mayo Clinic, Rochester, MN, USA and the AIRC-Gruppo Italiano Malattie Mieloproliferative (AGIMM), with the intent to examine i) survival trends, ii) treatment response rates and outcome and iii) risk factors for survival, including the impact of chemotherapy and allogeneic stem cell transplant (ASCT).Methods:Diagnoses of MPN, including primary myelofibrosis (PMF), polycythemia vera (PV), essential thrombocythemia (ET) and MPN-BP were according to WHO criteria (Blood 2016;127:2391). Treatment response to MPN-BP was assessed according to conventional criteria (JCO 2003;21:4642). Statistical analyses considered clinical and laboratory data collected at the time of documented disease transformation into MPN-BP. Survival was calculated from the date of leukemic transformation to the date of death or last contact. In order to examine survival trends, comparative analysis was performed based on year of leukemic transformation.Results:Mayo Cohort (n=248):1.Patient characteristics at time of leukemic transformation: The Mayo Clinic cohort consisted of 248 consecutive patients (median age 67 years; 65% males) with MPN-BP, including 118 (48%) post-PMF and 130 (52%) post-PV/ET MPN-BP; among the latter, 60 patients had post-PV (32 without documented MF phase) and 70 post-ET (39 without documented MF phase) MPN-BP. Among all evaluable cases, at the time of leukemic transformation, 34% displayed red cell transfusion dependency, 58% platelet count <100 x 10(9)/L, 37% leukocyte count >25 x 10(9)/L, 71% PB blasts ≥20%, 87% BM blasts ≥20%, 81% abnormal karyotype, 57% unfavorable karyotype and 68% JAK2 V617F mutation. Compared to post-PMF, post-PV/ET MPN-BP cases displayed female preponderance (p=0.04), lower transfusion need (p=0.0004), higher platelet count (p=0.004) and lower circulating blast count (p=0.005), but similar karyotype profile (p=0.3).2.Survival trends over time: After a median follow-up of 3 months (range 0-122), 226 (91%) deaths were recorded. Median overall survival (OS) was 3.6 months with 1- and 3-year survival rates of 17% and 6%, respectively; survival trends appeared significantly better (p=0.002) for patients diagnosed in the year 2000 and beyond, but with no additional improvement in more recent years (1-year survival rates for diagnosis before 2000 vs 2001-2009 vs 2010 and beyond were 5% vs 17% vs 20%, respectively).3.Treatment outcome and predictors of survival: Treatment response was assessable in 122 patients including 66 treated with acute myeloid leukemia (AML)-like induction chemotherapy, 26 with hypomethylating agents (HMA) and 30 with other agents; the respective complete remission (CR) rates were 35%, 4% and 3%; an additional 24% of patients who received AML-like induction chemotherapy achieved CR with incomplete blood count recovery (CRi) and their survival was similar to those with CR (p=NS); CRi was not seen with HMA. ASCT was reported in 24 patients and included 17 patients who received AML-like induction chemotherapy and 18 patients who were in CR or CRi, at time of transplant. In multivariable analysis, platelets <100 x 10(9)/L (HR 1.7; 95% CI 1.0-2.7) and unfavorable karyotype (HR 2.3; 95% CI 1.3-4.3) predicted inferior and achievement of CR/CRi (HR 0.4; 95% CI 0.2-0.7) superior survival; additional significance was not evident for ASCT (p=0.09). A composite assessment revealed that short-term survival was similarly and positively affected by either achieving CR/CRi or receiving ASCT, but the benefit did not endure (Figure).AGIMM cohort (n=171):An external cohort of 171 patients from AGIMM was used to validate most of the aforementioned observations from the Mayo Cohort (details to follow at time of presentation).Conclusions: CR or CRi is achievable in MPN-BP, but only with AML-like induction chemotherapy and not with HMA; achievement of CR/CRi was associated with improved short-term survival, regardless of consolidation with ASCT. Outcome after ASCT was not affected by pre-transplant chemotherapy and neither ASCT nor achievement of CR/CRi resulted in durable survival benefit. [Display omitted] DisclosuresPassamonti:Novartis Pharmaceuticals Corporation: Consultancy, Honoraria, Speakers Bureau. Rambaldi:Novartis, Roche/Genentech, Amgen, Italfarmaco: Consultancy; Novartis, Amgen, Celgene, Sanofi: Other: Travel, Accomodations, Expenses. Vannucchi:Novartis: Honoraria, Speakers Bureau; Shire: Speakers Bureau.

Treatment Evolution for Multiple Myeloma before Autologous Stem Cell Transplant and Its Relation with Engraftment Syndrome: 15 Years of Experience

▪BACKGROUNDMultiple Myeloma (MM) is among the diseases that obtain major benefits from upfront chemotherapy followed by High Dose Chemotherapy with Autologous Stem Cell Transplant (HDC-ASCT), in eligible patients. The treatment landscape for MM has significantly evolved over the last decade, making significant improvements in disease control before reaching HDC-ASCT. New and very efficient drugs are now designed to target immunoregulatory pathways interfering more specifically with malignant cells. Certainly, with this novel approach, new outcomes are expected to arise over time. Indeed, engraftment syndrome (ES) is seen more often and recognized in up to 70% in some series. Much has been proposed regarding the etiology of ES, but unfortunately little has been validated.The objective of this study was to identify the incidence, risk factors associated with the development of ES and the impact of this outcome on survival.METHODSPatients with MM who underwent HDC-ASCT from 2000 to 2015 at the San Antonio VA Hospital were included. ES was defined according to Maiolino criteria. Patients were divided into two groups, those who developed ES and those who did not. We analyzed pre-transplant chemotherapy regimen (PTR) and radiation therapy (RT) if any, administered to both groups. PTR was stratified as single line therapy (SLT) or multiple lines of therapy (MLT). The groups were comparable and matched for for age, gender, race and disease status at transplant. Survival was determined from the day of transplant. Frequency among variables and predictive analysis were evaluated by the Pearson's Chi-square test and logistic regression followed by Cox regression model respectively.RESULTSA total of 313 patients were included and out of those, 162 (51.8%) developed ES.208 patients (66.5%) received SLT and 105 (33.5%) MLT. Some form of radiation therapy (RT) was indicated in 72 (23.0%) patients for bone lesions, plasmacytoma or palliation of pain.The frequency of ES was significantly increased in those who received Bortezomib/Dexamethasone (VD) or Lenalinomide-Dexamethasone (RD) as SLT plus RT compared to those who received any other SLT or MLT (p=0.0138). The survival at 25 percentile of ES vs. no ES was 42 months vs. 30 months (p=0.0247). ES was seen more frequent in Whites and Hispanics compared to African Americans (AA) (p=0.0001 and p<0.0198, respectively).CONCLUSIONSPatients who received PTR with VD or RD plus any RT indicated for MM had increased frequency of ES. Patients who developed ES during transplant survived significantly longer. Whites and Hispanics had higher odds of developing ES compared to AA. The association of VD or VD plus RT has not been reported in the past as risk factor for ES in the era of immunomodulatory agents. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Should patients receive consolidation chemotherapy before reduced intensity allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia in first complete remission?

Background:For acute myeloid leukemia (AML) patients, the role of bridging consolidation chemotherapy after achieving first complete remission (CR1) in the transplant setting is a frequently debated issue. The lack of data from Asian patients led us to conduct this study.Methods:We retrospectively studied outcomes of 106 patients in CR1 undergoing allogeneic stem cell transplantation (alloSCT) with reduced intensity conditioning (RIC) based on their exposure to pre-transplant consolidation chemotherapy. There were 35 in the no consolidation group versus 71 in the consolidation group.Results:The median relapse free survival (RFS) was 9 months for the no consolidation group and 51 months for consolidation group (p = 0.023). The median overall survival was 32 months for the no consolidation group and not reached for the consolidation group (p = 0.034). Multivariate analysis recognized consolidation and poor cytogenetics as adverse prognostic factors for RFS. Moreover, RFS was better in patients with a shorter time lapse between last chemotherapy and alloSCT in both the no consolidation group and the consolidation group. Consolidation chemotherapy did not negatively affect neutrophil and platelet engraftment, infection rates, or acute graft-versus-host disease (GVHD) incidence. On the other hand, patients undergoing consolidation chemotherapy showed trends towards a more severe degree of chronic GVHD.Conclusion:The exposure to consolidation chemotherapy in CR1 prior to alloSCT with RIC conditioning did not negatively impact the outcomes in Korean AML patients, for whom a suitable donor is rarely immediately available. Therefore, post-remission consolidation chemotherapy is a reasonable option if required.

Bortezomib-Based Induction Is Associated with Superior Outcomes in Light Chain Amyloidosis Patients Treated with Autologous Hematopoietic Cell Transplantation Regardless of Plasma Cell Burden

The benefits of pre-transplant induction chemotherapy in light chain (AL) amyloidosis, a low burden plasma cell (PC) neoplasm associated with multiorgan dysfunction, is debatable, although with the availability of bortezomib, this approach is being increasingly pursued. We analyzed the outcomes of AL amyloidosis patients undergoing autologous hematopoietic cell transplant between 2014 and 2018 that were reported to the Center for International Blood and Marrow Transplant Research database. Of 440 patients, 294 received bortezomib-based induction, and 146 received no induction. Patients receiving induction had greater PC burden compared to no induction (PC 10% or more, 39% versus 11%; P < .01). At 2 years, the induction group compared to no induction had lower relapse/progression: 13% (9% to 18%) versus 23% (16% to 32%) (P = .02); better progression-free survival (PFS): 82% (77% to 87%) versus 69% (61% to 77%) (P < .01); and similar overall survival (OS): 92% (88% to 95%) versus 89% (84% to 94%) (P = .22), findings that were confirmed on multivariate analysis. A subset analysis limited to patients with <10% PC also showed superior relapse/progression (hazard ratio [HR], .43; 95% confidence interval [CI], .24 to .78; P < .01) and PFS (HR, .43; 95% CI, .26 to .72; P < .01) for induction compared to no induction. Thus, we conclude that pre-transplant bortezomib-based induction was associated with improved relapse/progression and PFS in AL amyloidosis. Longer survival follow-up is warranted, as OS was excellent in both cohorts at 2 years.

Detection of Abnormal Pretransplant Clones in Progenitor Cells of Patients Who Developed Myelodysplasia After Autologous Transplantation

AbstractSecondary myelodysplastic syndromes (MDS) have been reported after autologous transplantation. It is not known whether the MDS results from the pretransplant conventional-dose chemotherapy or from the high-dose chemotherapy (HDC) used for the transplant procedure. We performed a multicenter, retrospective analysis of morphologically normal pretransplant marrow or stem cell specimens from 12 patients who subsequently developed myelodysplasia after HDC. To determine if the abnormal clone was present before HDC, we used fluorescence in situ hybridization (FISH) to detect the cytogenetic markers observed at the onset of posttransplant MDS. Cryopreserved, pretransplant bone marrow, peripheral blood stem cell specimens, obtained at the time of harvest, or archival smears were used. Standard cytogenetic analysis had been performed pretransplant in four patients, showing a normal karyotype. In 9 of 12 cases, the same cytogenetic abnormality observed at the time of MDS diagnosis was detected by FISH in the pre-HDC specimens. Our findings support the hypothesis that, in many cases of posttransplant MDS, the stem cell damage results from prior conventional-dose chemotherapy and may be unrelated to HDC or the transplantation process itself.

Value of pre-transplant consolidation chemotherapy in adults with acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation without minimal residual disease in first complete remission

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is recommended for adults acute lymphoblastic leukemia (ALL) with minimal residual disease (MRD) negative during their first complete remission (CR1). However, the role of pre-transplant consolidation chemotherapy remains unclear. We evaluated 78 CR1/MRD-negative patients, the consolidation and non-consolidation groups had similar 5-year OS (74.8% [95% CI: 62.2–87.3%] vs. 74.2% [95% CI: 53.2–95.1%], p = .894), RFS (72.2% [95% CI: 59.6–84.7%] vs. 73.1% [95% CI: 54.2–91.9%], p = .942), CIR (9.4% [95% CI: 9.1–9.7%] vs. 18.9% [95% CI: 17.3–20.4%], p = .376), and NRM (18.4% [95% CI: 17.7–19.0%] vs. 8.0% [95% CI: 7.3–8.6%], p = .375). Multivariable analysis confirmed that high cytogenetic risk independently predicted poor OS and RFS, although pre-transplant consolidation chemotherapy did not predict the prognosis. Based on these findings, we recommend performing transplantation immediately for adult ALL patients after they have achieved CR1/MRD-negative status when there are readily available donors.

Post-remission therapy of adults aged 60 and older with acute myeloid leukemia in first complete remission: role of treatment intensity on the outcome.

Although complete remission (CR) is achieved in 50 to 70% of older fit patients with acute myeloid leukemia (AML), consolidation therapy in this age group remains challenging. In this retrospective study, we aimed to compare outcome in elderly patients treated with different post-remission modalities, including allogenic and autologous hematopoietic stem cell transplantation (HSCT), intensive chemotherapy, and standard-dose chemotherapy (repeated 1 + 5 regimen). We collected data of 441 patients ≥ 60years in first CR from a single institution. Median age was 67years. Sixty-one (14%) patients received allo-HSCT, 51 (12%) auto-HSCT, 70 (16%) intensive chemotherapy with intermediate- or high-dose cytarabine (I/HDAC), and 190 (43%) 1 + 5 regimen. Median follow-up was 6.5years. In multivariate analysis, allo-HSCT, cytogenetics, and PS had a significant impact on OS and LFS. In spite of a more favorable-risk profile, the patients who received I/HDAC had no significantly better LFS as compared with patients treated with 1 + 5 (median LFS 8.8months vs 10.6months, p = 0.96). In transplanted patients, median LFS was 13.3months for auto-HSCT and 25.8months for allo-HSCT. Pre-transplant chemotherapy with I/HDAC had no effect on the outcome. Toxicity was significantly increased for both transplanted and non-transplanted patients treated with I/HDAC, with more units of blood and platelet transfusion and more time spent in hospitalization, but no higher non-relapse mortality. This study shows that post-remission chemotherapy intensification is not associated with significantly better outcome as compared with standard-dose chemotherapy in elderly patients for whom, overall results remain disappointing.

Outcomes of 138 myelodysplastic syndrome patients with HLA-matched sibling donor allogeneic hematopoietic stem cell transplantation

目的评价人组织相容性抗原（HLA）匹配同胞供者外周血干细胞移植（MSD-PBSCT）治疗骨髓增生异常综合征（MDS）的疗效。方法回顾性总结2005年9月至2017年12月接受MSD-PBSCT治疗的138例MDS患者临床资料，观察患者总生存（OS）率、无病生存（DFS）率、复发（RR）率及非复发死亡率（NRM），分析影响移植预后的危险因素。结果①中位随访1 050（4~4 988）d，3年OS率、DFS率分别为（66.6±4.1）%、（63.3±4.1）%，3年累积RR率、NRM分别为（13.9±0.1）%、（22.2±0.1）%。②单因素分析显示，发生Ⅲ~Ⅳ度急性移植物抗宿主病（aGVHD）、造血干细胞移植合并症指数（HCT-CI）≥2分组和修订的国际预后积分系统（IPSS-R）极高危组的OS率均显著降低[（42.9±13.2）%对（72.9±4.2）%，χ2=8.620，P=0.003；（53.3±7.6）%对（72.6±4.7）%，χ2=6.681，P=0.010；（53.8±6.8）%对（76.6±6.2）%、（73.3±7.7）%，χ2=6.337，P=0.042]。MDS伴有原始细胞过多-2（MDS-EB2）和MDS转化急性髓系白血病（MDS-AML）患者，移植前接收化疗或去甲基化治疗不改善OS[（60.4±7.8）%对（59.2±9.6）%，χ2=0.042，P=0.838]。③多因素分析显示，HCT-CI是影响移植后OS和DFS的独立危险因素（P=0.012，HR=2.108，95%CI 1.174~3.785；P=0.008，HR=2.128，95%CI 1.219~3.712）。结论HCT-CI评价MDS患者移植后预后优于IPSS-R预后分组；发生Ⅲ~Ⅳ度aGVHD是影响移植后OS的不良预后因素；MDS-EB2和MDS-AML患者可以不化疗直接行MSD-PBSCT。

Effect of consolidation before allogeneic hematopoietic stem cell transplantation for non-favorable acute myeloid leukemia patients with first complete remisson and negative minimal residual disease

目的探讨异基因造血干细胞移植（allo-HSCT）前巩固化疗对第1次形态学完全缓解且微小残留病阴性（CR1/MRD−）中/高危急性髓系白血病（AML）患者预后的影响。方法对2010年1月至2019年3月在CR1/MRD−状态下接受allo-HSCT的155例中/高危AML（不含急性早幼粒细胞白血病）患者进行回顾性分析。结果全部155例患者中，102例获得CR1/MRD−后接受移植前巩固化疗（巩固组），53例获得CR1/MRD−后直接行allo-HSCT（非巩固组），两组中位年龄分别为39（18~56）岁、38（19~67）岁。巩固组、非巩固组移植后5年总生存率分别为（59.3±7.5）%、（62.2±6.9）%（P=0.919），无复发生存率分别为（53.0±8.9）%、（61.6±7.0）%（P=0.936），累积复发率分别为（21.9±5.4）%、（18.3±6.0）%（P=0.942），非复发死亡率分别为（22.4±4.3）%、（28.4±6.5）%（P=0.464）。多因素分析显示，移植前是否接受巩固化疗及其疗程（<2个/≥2个）对预后无显著影响。结论中/高危AML患者可在获得CR1/MRD−后直接进行allo-HSCT。

Improvement of Survival in JMML By Induction Regimen of Decitabine + Cytarabine + Fludarabine before Hematopoietic Stem Cell Transplantation: Study of 33 Cases in Single Center

OBJECTIVE: Pre-transplant chemotherapy can control progression of primary disease, alleviate disease and improve disease-free survival after transplantation in juvenile granulocyte leukemia (JMML).Methylation abnormalities play an important role in the development of JMML. This study was to explore the effectiveness of induction regimen including decitabine ,cytarabine and fludarabine before transplantation and to explore the affection to transplantation in JMML. METHODS: A retrospective analysis of the remission and survival of 33 children with JMML before and after stem cell transplantation in the Department of Pediatrics of Nanfang Hospital from 2014.2 to 2019.7. There were fourteen girls and 19 boys, median diagnosis age 23 months(2m-10 years old). Median white blood cell count,median hemoglobin level,median platelet count( WBC) was 29.3G/L (6.29-158.66G/L); 83g /L(41-113g/L,); 27.17G / L(4-431G / L) respectively. Median Hemoglobin F level was 34.16%( 1.56-78%). Median spleen level under the costal margin was 5cm(0-13.3cm); Median liver under the costal margin was 3.9 cm(0 -8.9 cm) .There were 26 cases with the pulmonary involvement (26/33, 78.8%). The original blast cells in bone marrow were 0-8.8%, with a median of 4.5%.Mutant genes including: 2 cases of KAS, 9 cases of NF1, 2 cases of NRAS, 16 cases of PTPN11, and 4 cases without common JMML gene .The first course of treatment after diagnosis is 20 mg/m2 × 5 days of decitabine. The second course of treatment is DA: decitabine 20 mg/m2 × 5 days + cytarabine 100 mg/m2 × 5 days or A-3V regimen: Ara-C 100 mg/m2/d CIV×7 days+Etoposide 100 mg/m2/d ×5 days+Vincristine 1.5 mg/m2/d ×1 day. The third course of treatment is decitabine 20 mg/m2 × 5 days,then FLAG regimen: Fludarabine 30mg / m2 × 5 days, Ara-C 1 g / m2 × 5 days, G-CSF 5μg / Kg × 6 days. Single drug of decitabine 20 mg/m2 × 5 days was adminstered 1-3 times per monthly during the period of waiting for transplantation. Comprehensive assessment was performed before transplantation. Survival outcomes were analyzed by Kaplan-Meier curves. RESULTS: At least 3 courses of chemotherapy were completed in 33 cases, including 1-5 courses of decitabine.The bone marrow was evaluated in 31 patients before transplantation: 12 patients got complete remission(CR) and 19 patients got partial remission(PR) .Peripheral blood evaluation: 23 cases achieved WBC CR; 17 cases achieved platelet CR, 6 cases achieved platelet PR, 7 cases had no improvement. Eighteen cases of spleen were evaluated, of which only 3 cases were CR, 13 cases were PR, and 2 cases did not improve. Overall assessment, only 1 case achieved CR before transplantation, 1 case did not improve, and 31 cases achieved PR .Allogeneic hematopoietic stem cell transplantation was performed in 33 cases, including 3 cases of nonrelated peripheral blood hematopoietic stem cell transplantation(PB HSCT), 30 cases of complementary transplantation (haploid identical PB HSCT plus non-related cord blood transplantation). The median follow-up time after transplantation was 22m(3-63m).There was no death in the period of chemotherapy before transplantation. Four patients relapsed after transplantation, and One patient died of transplantation related death. Three years EFS was 80.6%. Conclusion: Pre-transplant chemotherapy based on regimen of decitabine + cytarabine + fludarabine is safe, effective and feasible. The response rate of treatment is 97.0%, although the complete remission rate before transplantation is low, most of them are partial remission, but the disease-free survival after non-related HSCT or complementary transplantation could reached to 80.6%. These results indicated that pre-transplant chemotherapy based on regimen of decitabine + cytarabine + fludarabine was benefit to improved the survival of children with JMML after HSCT. Figure 1 Disclosures No relevant conflicts of interest to declare.

Hematopoietic Stem Cell Transplantation for Primary Immunodeficiencies.

The field of primary immunodeficiencies has pioneered many of the advances in haematopoietic stem cell transplantation and cellular therapies over the last 50 years. The first patients to demonstrate sustained benefit and prolonged cure from the primary genetic defect following allogeneic haematopoietic stem cell transplantation were patients with primary immunodeficiencies. Although primary immunodeficiency patients began the modern era of haematopoietic stem cell transplantation, the history is nevertheless short-in answer to the question “what is the long term outcome of patients transplanted for primary immunodeficiencies?” we often have to say that we do not know. We believe that most patients who undergo haematopoietic stem cell transplantation for primary immunodeficiencies should live a normal lifespan with a fully corrected immune system. We are now beginning to understanding long term outcomes, the relationship to the underlying genetic defect, age, and pre-morbid condition of the patient at time of transplantation, stem cell source and donor, and effect of pre-transplant cytoreductive chemotherapy conditioning. The long term consequences of post-transplant complications such as graft vs. host disease, veno-occlusive disease, or immune dysregulation are also being recognized. Additionally, some genetic defects have a systemic distribution, and we are learning the natural history of these defects once the immunodeficiency has been removed.