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Patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) after, or ineligible for, autologous stem cell transplantation (ASCT) have a dismal prognosis. This phase II study evaluated treatment with R-PECC (rituximab, prednisolone, etoposide, chlorambucil, lomustine), every 28 days for 4 cycles in 62 patients, followed by radio-immunotherapy consolidation with 90 Y-ibritumomab tiuxetan in responsive patients. Primary endpoints were failure-free survival (FFS) and incidence of grade ≥3 adverse events from start of 90 Y-ibritumomab tiuxetan. The overall response rate after R-PECC was 50%. Twenty-nine of 31 responsive patients proceeded to 90 Y-ibritumomab tiuxetan. Five out of 15 partial remission patients converted to complete remission after 90 Y-ibritumomab tiuxetan. One-year FFS and overall survival (OS) from start of 90 Y-ibritumomab tiuxetan was 52% (95% confidence interval [CI], 33-68%) and 62% (95% CI, 42-77%), respectively. One-year FFS and OS from start of R-PECC was 28% (95% CI, 17-39%) and 49% (95% CI, 36-61%), respectively. Toxicities of R-PECC and 90 Y-ibritumomab tiuxetan were mainly haematological. In conclusion, for relapsed DLBCL patients the largely oral R-PECC regimen achieves promising response rates, combined with an acceptable safety profile. Consolidation with 90 Y-ibritumomab tiuxetan resulted in long-term response durations in approximately one third of the patients that received it., (© 2019 British Society for Haematology and John Wiley & Sons Ltd.)

Patients with relapsed follicular lymphoma (FL) following first-line therapy have an increasing number of management strategies ranging from observation through to stem cell transplantation. There has been an exciting expansion in novel agents to treat FL, but at present there is not a universally accepted standard of care in the relapse setting. Decision-making can be difficult for the clinician as there is a paucity of data to compare the various relapse therapies available. This review will discuss conventional therapy for relapsed FL, consider the use of novel agents and explore the role and timing of autologous and allogeneic stem cell transplantation.

Background: The objective of the current study was to investigate the role of postremission consolidation chemotherapy before reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (alloSCT) for patients with acute myeloid leukemia (AML) in first complete remission (CR1)., Methods: Of the 789 consecutive patients with AML in CR1 who underwent RIC alloSCT from a human leukocyte antigen-matched sibling or matched unrelated donor peripheral stem cell grafts between 2001 and 2010, 591 patients received at least 1 cycle of consolidation chemotherapy and 198 patients did not receive any consolidation chemotherapy before alloSCT. To minimize inherent survival bias in favor of patients who underwent transplant long after achieving CR1, the study focused on 373 patients who underwent transplant within the median time frame between achievement of CR1 and alloSCT (3 months for patients who underwent alloSCT from matched siblings and 4 months for patients who underwent alloSCT from matched unrelated donors). In this subgroup, 151 patients did not receive any consolidation chemotherapy and 222 patients received ≥ 1 consolidation chemotherapy cycle., Results: With a median follow-up of 36 months (range, 2 months-135 months), the 3-year cumulative recurrence incidence (RI) was not significantly different between the groups (36% ± 4% for the group treated without consolidation chemotherapy vs 38% ± 3% for patients who received consolidation chemotherapy; P = .89). In addition, leukemia-free survival was similar between the groups (45% ± 4% and 47% ± 3%, respectively; P = .41). Dose intensity of cytarabine given during consolidation chemotherapy appeared to have no influence on RI. On multivariate analysis, pretransplant consolidation (≥ 1 cycle vs 0 cycles) was found to have no significant impact on RI (hazards ratio, 1.29; 95% confidence interval, 0.84-1.97 [P = .24]) or leukemia-free survival (hazards ratio, 1.00; 95% confidence interval, 0.71-1.42 [P = .99])., Conclusions: The data from the current study suggest no apparent advantage for postremission consolidation chemotherapy before RIC alloSCT, provided a donor is readily available., (© 2013 American Cancer Society.)

Purpose: To analyze the outcome, including nonrelapse mortality (NRM), relapse rate (RR), progression-free survival (PFS), and overall survival (OS), of patients with diffuse large B-cell non-Hodgkin's lymphoma (DLBCL) relapsed after an autologous stem-cell transplantation (ASCT) and treated with an allogeneic stem-cell transplantation (allo-SCT)., Patients and Methods: The European Group for Blood and Marrow Transplantation database was scanned for a first allo-SCT in relapsed DLBCL after a previous ASCT between 1997 and 2006. Other inclusion criteria were age at allo-SCT ≥ 18 years and availability of an HLA-identical sibling or a matched unrelated donor. A total of 101 patients (57 males; median age, 46 years) were included. Median follow-up for survivors was 36 months., Results: Myeloablative conditioning regimen was used in 37 patients and reduced intensity conditioning (RIC) was used in 64 patients. Three-year NRM was 28.2% (95% CI, 20% to 39%), RR was 30.1% (95% CI, 22% to 41%), PFS was 41.7% (95% CI, 32% to 52%), and OS was 53.8% (95% CI, 44% to 64%). NRM was significantly increased in patients ≥ 45 years (P = .01) and in those with an early relapse (< 12 months) after ASCT (P = .01). RR was significantly higher in refractory patients (P = .03). A time interval to relapse after ASCT of < 12 months was associated with lower PFS (P = .03). The use of RIC regimens was followed by a trend to a lower NRM (P = .1) and a trend to a higher RR (P = .1), with no differences in PFS and OS. No differences were seen between HLA-identical siblings and matched unrelated donors., Conclusion: Allo-SCT in relapsed DLBCL after ASCT is a promising therapeutic modality. Patients with a long remission after ASCT and with sensitive disease at allo-SCT are the best candidates for this approach.

Background and Objectives: Chromosome 5 and/or 7 abnormalities are cytogenetic findings indicative of a poor prognosis in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). The only potential cure for such patients is allogeneic stem cell transplantation (SCT). As data on allogeneic SCT in this context are limited we did a retrospective study of allogeneic SCT in patients with AML or MDS who had chromosome 5 and/or 7 abnormalities., Design and Methods: This was a retrospective study of 65 patients (16 children, 49 adults) with AML (n=33) or MDS (n=32) who had chromosome 5 and/or 7 abnormalities and who underwent allogeneic SCT in six Dutch Centers between 1983 and 2001. Data on all these patients are recorded in the Netherlands Stem Cell Transplant Registry (Typhon)., Results: The 3-year overall survival rate among all patients was 25%. Patients below the age of 40 years had significantly fewer relapses (40%) and better survival (38%) than those above the age of 40 (86% and 8%, respectively). Relapses were less frequent in recipients of unrelated grafts than in those whose grafts were from HLA-identical siblings (30% versus 69%). The development of acute graft-versus-host disease (GVHD) grades II-IV was independently associated with significantly higher transplant-related mortality (TRM). Patients with either chromosome 5 or chromosome 7 abnormalities had a significantly better survival than patients with both chromosome 5 and 7 abnormalities. These patients with poor-risk chromosome 5 and/or 7 abnormalities were compared with a group of patients with a secondary AML/MDS and normal cytogenetics and were found to have significantly more relapses and significantly worse survival but a similar TRM., Interpretation and Conclusions: We conclude that patients with AML or MDS with chromosome 5 and/or 7 abnormalities do rather poorly after allogeneic SCT, mainly because of the very high relapse rate. Nevertheless, this is the only approach that can cure some of these patients.

Purpose: To determine, in a randomized clinical trial, whether high-dose therapy (HDT) followed by autologous stem-cell transplantation is more effective than standard treatment with regard to progression-free survival (PFS) and overall survival (OS) in patients with relapsed follicular non-Hodgkin's lymphoma; and to assess the additional value of B-cell purging of the stem-cell graft with regards to PFS and OS., Patients and Methods: Patients received three cycles of chemotherapy. Responding patients with limited bone marrow infiltration were eligible for random assignment to three further cycles of chemotherapy (C), unpurged HDT (U), or purged HDT (P)., Results: Between August 1993 and April 1997, 140 patients were registered from 36 centers internationally, and 89 were randomly assigned. Reasons for not randomizing included patient refusal, early progression, or death on induction therapy. With a 69-month median follow-up, the log-rank P value for PFS and OS were.0037 and.079, respectively. For PFS, the hazard ratios (95% CIs) for U versus C, P versus C, and P versus U were 0.33 (0.16 to 0.70), 0.38 (0.19 to 0.79), and 1.02 (0.51 to 2.05), respectively. The hazard ratio (95% CI) for C versus U + P was 0.30 (0.15 to 0.61). Hazard ratios (95% CIs) for OS were 0.43 (0.18 to 1.06), 0.43 (0.18 to 1.02), and 0.72 (0.32 to 1.63). For C versus U + P, the hazard ratio (95% CI) was 0.40 (0.18 to 0.89). Kaplan-Meier estimates (95% CIs) of 2-year PFS for C, U, and P were 26% (8% to 44%), 58% (37% to 79%), and 55% (34% to 75%), respectively. OS at 4 years for C, U, and P are 46% (25% to 67%), 71% (52% to 91%), and 77% (60% to 95%) respectively., Conclusion: HDT significantly improves PFS and OS. There is no clear evidence of benefit through purging.

Hematopoietic stem cell transplantation is an important treatment for many malignant hematological and non-hematological diseases. Survivors of hematopoietic stem cell transplantation (HCT) are at risk of long-term health problems and reduced quality of life related to previous treatments. Many studies about these long-term effects have been conducted over the last decades. However, selection bias is a concern in long-term follow-up studies and little is known about the non-participating group. As part of the Maastricht Observational study of late effects after Stem cell trAnsplantation (MOSA), investigating long-term health effects by extensively phenotyping HCT survivors, we conducted a survey to characterise the non-participating group. This survey mostly focused on quality of life and physical complaints. The survey responders were generally older than the MOSA group, had more history of relapsed disease, and described their general health as bad or mediocre significantly more often than the MOSA group. Also, more deaths occurred in the group of non-participants between the start of study inclusion in 2015 and analysis of the survey results in 2021. This study suggests that a selection of higher functioning HCT survivors with a relatively better quality of life participated in this long-term follow-up study of stem cell transplantation survivors. These results could also impact the results of other long-term follow-up studies in cancer survivors, knowing that possibly an unhealthier population is missed in these studies and some long-term negative effects of treatments might be underestimated. Trial registration number: NL-48599. [ABSTRACT FROM AUTHOR]

Summary: Patients with relapsed/refractory diffuse large B‐cell lymphoma (DLBCL) after, or ineligible for, autologous stem cell transplantation (ASCT) have a dismal prognosis. This phase II study evaluated treatment with R‐PECC (rituximab, prednisolone, etoposide, chlorambucil, lomustine), every 28 days for 4 cycles in 62 patients, followed by radio‐immunotherapy consolidation with 90Y‐ibritumomab tiuxetan in responsive patients. Primary endpoints were failure‐free survival (FFS) and incidence of grade ≥3 adverse events from start of 90Y‐ibritumomab tiuxetan. The overall response rate after R‐PECC was 50%. Twenty‐nine of 31 responsive patients proceeded to 90Y‐ibritumomab tiuxetan. Five out of 15 partial remission patients converted to complete remission after 90Y‐ibritumomab tiuxetan. One‐year FFS and overall survival (OS) from start of 90Y‐ibritumomab tiuxetan was 52% (95% confidence interval [CI], 33–68%) and 62% (95% CI, 42–77%), respectively. One‐year FFS and OS from start of R‐PECC was 28% (95% CI, 17–39%) and 49% (95% CI, 36–61%), respectively. Toxicities of R‐PECC and 90Y‐ibritumomab tiuxetan were mainly haematological. In conclusion, for relapsed DLBCL patients the largely oral R‐PECC regimen achieves promising response rates, combined with an acceptable safety profile. Consolidation with 90Y‐ibritumomab tiuxetan resulted in long‐term response durations in approximately one third of the patients that received it. [ABSTRACT FROM AUTHOR]

Induction of donor-specific hyporesponsiveness would minimize the need for intensive immunosuppression in the clinical setting of graft rejection and dendritic cells (DCs) might be useful tools for this purpose. Besides their ability to induce immunogenic T-cell responses, these antigen presenting cells can lead to T-cell anergy, when antigen presentation occurs in the absence of costimulation as is the case in immature DCs (iDCs). In continuance of publications reporting on the use of iDCs to induce tolerance to various organs, we set out to determine whether tolerance could be induced in a model of allogeneic stem cell transplantation. Immature DCs were obtained by culture with very low concentrations of GMCSF and by treating DCs with Dexamethasone (Dex). We show that these DCs express low levels of MHCII and costimulatory molecules and that this immature phenotype is retained after application of maturation stimuli. We also prove that these alternatively activated DCs are unable to induce T-cell proliferation in vitro. When used in vivo however, these tolerogenic DCs do not provide tolerance to fully mismatched or haploidentical stem cells. [ABSTRACT FROM AUTHOR]

Background: Although increasing data are available on quality of life (QOL) issues after stem cell transplantation (SCT), many issues are still unresolved. With the increasing use of transplants in non-curative situations, quality of life issues have become especially important. Methods: All patients who had undergone SCT and had no recurrent disease were asked to provide quality of life data using the EORTC QLQ-C30 questionnaire at about 2.5 (n=52) and 4.5 years (n=33) after transplantation. In addition, the patients’ partners and physicians were asked to estimate the patients’ quality of life. Results: Scores on the functional scales ranged from 65 to 80 and were comparable initially and at the 23-month follow-up. The initial, overall quality of life of the patients was 75. After an additional 23-month follow-up, the overall quality of life was 73. Fatigue, sleeping disturbances, and financial problems scored relatively high. Generally, in contrast to partners, physicians underestimated symptoms and overestimated functions and quality of life significantly. Conclusions: We conclude that SCT has a long-term impact on such quality of life issues as fatigue, sleep disturbances, dyspnea, and financial problems. Physicians tend to overestimate quality of life in their patients. With the increasing numbers of patients undergoing transplantation, more attention should be focussed on these issues. [Copyright &y& Elsevier]

Background: Experience using post-transplant cyclophosphamide (PT-Cy) as graft-versus-host disease (GVHD) prophylaxis in allogeneic stem cell transplantation (HSCT) from matched sibling donors (MSD) or unrelated donors (UD) is limited and with controversial results. The study aim was to evaluate PT-Cy as GVHD prophylaxis post-HSCT from MSD and UD transplants. We analyzed 423 patients with acute leukemia who received PT-Cy alone or in combination with other immunosuppressive (IS) drugs as GVHD prophylaxis. Seventy-eight patients received PT-Cy alone (group 1); 204 received PT-Cy in combination with one IS drug—cyclosporine-A (CSA) or methotrexate (MTX) or mycophenolate-mofetil (MMF) (group 2), while 141 patients received PT-Cy in combination with two IS drugs—CSA + MTX or CSA + MMF (group 3). Transplants were performed from 2007 to 2015 and median follow-up was 20 months. Results: Probability of overall survival (OS) at 2 years was 50, 52.2, and 62.4%, for the three groups, respectively, p = 0.06. In multivariate analysis, in comparison to PT-Cy alone, the addition of two IS drugs was associated with reduced risk of extensive cGVHD (HR 0.25, p = 0.02). Use of bone marrow (BM) and anti-thymocyte globulin were independently associated with reduced risk of extensive cGVHD. Prognostic factors for non-relapse mortality (NRM) were the addition of two IS drugs to PT-Cy (HR 0.35, p = 0.04), diagnosis of AML, disease status at transplant, and patient CMV serology. Factors associated with increased OS were the use of PT-Cy with two IS drugs (HR 0.49, p = 0.02), AML, and disease status at transplant. Conclusion: For GVHD prophylaxis in MSD and UD HSCT, the addition of IS drugs to PT-Cy enhances its effect and reduces the risk of severe cGVHD, reducing mortality and improving survival. [ABSTRACT FROM AUTHOR]

Recombination events have been reported between HLA-A/C, HLA-B/DRB1 and HLA-DQB1/DPB1. To our knowledge no proven recombination event between HLA-B and -C has ever been found. In a sibling of a stem cell transplant candidate, the candidate and 3 siblings were typed and a pedigree with 4 different haplotypes could be established, but with very rare B-C segregation patterns (B*35∼C*05, B*44∼C*04). We performed STR analysis (Identifiler, ABI) to confirm sib relationship amongst the 4 individuals. If common HLA-B ∼C associations (B*35∼C*04, B*44∼C*05) were considered, 3 haplotypes could be identified and segregation patterns revealed one common haplotype for all individuals and the occurrence of a C/B recombination in one of the individuals. To investigate this possibility STR analysis was performed with informative markers D6S2838, D6S2851 (telomeric of HLA-A), D6S510, D6S265, D6S2931 (between HLA-A and -C), D6S2811, D6S2928 (between HLA-C and -B), MIB, D6S2792, D6S2787, D6S2920, D6S2894, D6S2883 (between HLA-B and -DRB1), D6S1666 and G51152 (centromeric of HLA-DQB1). The individual with the possible recombination event showed STR markers identical to one sibling with the same HLA-A and -C typing up to marker D6S2928, whereas the markers between HLA-B and -DRB1 and telomeric of DQB1 were identical to the other two siblings with identical HLA-B, -DRB1 and -DQB1 typing results. The region of the recombination was further narrowed by sequencing the area between HLA-B and D6S2928. This showed the recombination event to have taken place in the highly conserved sequence between 847 and 1228 bases after the HLA-B STOP codon. In conclusion, this is the first report confirming a recombination event between HLA-B and -C identified in a family of a stem cell transplant candidate. [ABSTRACT FROM AUTHOR]

We studied the outcome of allogeneic hematopoietic stem cell transplantation after lower-intensity conditioning regimens (reduced-intensity conditioning and nonmyeloablative) in patients with non-Hodgkin lymphoma who relapsed after autologous hematopoietic stem cell transplantation. Nonrelapse mortality, lymphoma progression/relapse, progression-free survival (PFS), and overall survival were analyzed in 263 patients with non-Hodgkin lymphoma. All 263 patients had relapsed after a previous autologous hematopoietic stem cell transplantation and then had undergone allogeneic hematopoietic stem cell transplantation from a related (n = 26) or unrelated (n = 237) donor after reduced-intensity conditioning (n = 128) or nonmyeloablative (n = 135) and were reported to the Center for International Blood and Marrow Transplant Research between 1996 and 2006. The median follow-up of survivors was 68 months (range, 3-111 months). Three-year nonrelapse mortality was 44% (95% confidence interval [CI], 37%-50%). Lymphoma progression/relapse at 3 years was 35% (95% CI, 29%-41%). Three-year probabilities of PFS and overall survival were 21% (95% CI, 16%-27%) and 32% (95% CI, 27%-38%), respectively. Superior Karnofsky Performance Score, longer interval between transplantations, total body irradiation-based conditioning regimen, and lymphoma remission at transplantation were correlated with improved PFS. Allogeneic hematopoietic stem cell transplantation after lower-intensity conditioning is associated with significant nonrelapse mortality but can result in long-term PFS. We describe a quantitative risk model based on pretransplantation risk factors to identify those patients likely to benefit from this approach. [ABSTRACT FROM AUTHOR]

Cytogenetics play a major role in determining the prognosis of patients with acute myelogenous leukemia (AML). However, existing cytogenetics classifications were developed in chemotherapy-treated patients and might not be optimal for patients undergoing allogeneic hematopoietic cell transplantation (HCT). We studied 821 adult patients reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) who underwent HCT for AML in first or second complete remission between 1999 and 2004. We compared the ability of the 6 existing classifications to stratify patients by overall survival. We then defined a new scheme specifically applicable to patients undergoing HCT using this patient cohort. Under this scheme, inv(16) is favorable, a complex karyotype (4 or more abnormalities) is adverse, and all other classified abnormalities are intermediate in predicting survival after HCT (5-year overall survival, 64%, 18%, and 50%, respectively; P = .0001). This scheme stratifies patients into 3 groups with similar nonrelapse mortality, but significantly different incidences of relapse, overall and leukemia-free survival. It applies to patients regardless of disease status (first or second complete remission), donor type (matched related or unrelated), or conditioning intensity (myeloablative or reduced intensity). This transplantation-specific classification could be adopted for prognostication purposes and to stratify patients with AML and karyotypic abnormalities entering HCT clinical trials. [ABSTRACT FROM AUTHOR]

We report the results of a prospective, randomized phase 3 trial evaluating autologous peripheral blood stem cell transplantation (ASCT) versus intensive consolidation chemotherapy in newly diagnosed AML patients in complete remission (CR1). Patients with AML (16-60 years) in CR1 after 2 cycles of intensive chemotherapy and not eligible for allogeneic SCT were randomized between intensive chemotherapy with etoposide and mitoxantrone or ASCT ater highdose cyclophosphamide and busulfan. Of patients randomized (chemotherapy, n = 259; ASCT, n = 258), more than 90% received their assigned treatment. The 2 groups were comparable with regard to prognostic factors. The ASCT group showed a markedly reduced relapse rate (58% vs 70%, P = .02) and better relapse-free survival at 5 years (38% vs 29%, P = .065, hazard ratio = 0.82; 95% confidence interval, 0.66-1.1) with nonrelapse mortality of 4% versus 1% in the chemotherapy arm (P = .02). Overall survival was similar (44% vs 41% at 5 years, P= .86) because of more opportunities for salvage with second-line chemotherapy and stem cell transplantation in patients relapsing on the chemotherapy arm. This large study shows a relapse advantage for ASCT as postremission therapy but similar survival because more relapsing patients on the chemotherapy arm were salvaged with a late transplantation for relapse. [ABSTRACT FROM AUTHOR]

Preservation of fertility after hematopoietic cell transplantation (HCT) can have a significant influence on the quality of life of transplant survivors. We describe 178 pregnancies in HCT recipients that were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) between 2002 and 2007. There were 83 pregnancies in female HCT recipients and 95 pregnancies in female partners of male HCT recipients. Indications for transplantation included hematologic and other malignancies (N = 99) and nonmalignant disorders (N = 79, of which 75 patients had severe aplastic anemia). The cohort included recipients of autologous HCT (20 women, 13 men), myeloablative (MA) allogeneic HCT (12 women, 50 men), and nonmyeloablative allogeneic HCT (2 women, 2 men). Age at HCT was <20 years for 50% of women and 19% of men. Conditioning regimens included total body irradiation (TBI) in 16% of women and 19% of men; doses were MA in 10% of women and in 16% of men. Live births were reported in 86% of pregnancies in partners of male transplant patients and 85% of pregnancies in female transplant patients, with most pregnancies occurring 5 to 10 years after HCT. We conclude that some HCT recipients can retain fertility, including patients who have received TBI and/or MA conditioning. Young patients undergoing HCT should be counseled both before and after HCT about potential loss of fertility, methods for preserving fertility, and planning for future pregnancy. Fertility and outcomes of pregnancy after HCT need prospective evaluation in large transplant cohorts. [ABSTRACT FROM AUTHOR]

Myelofibrosis is a myeloproliferative disorder incurable with conventional strategies. Several small series have reported long-term disease-free survival (DSF) after allogeneic hematopoietic cell transplantation (HCT). In this study, we analyze the outcomes of 289 patients receiving allogeneic transplantation for primary myelofibrosis between 1989 and 2002, from the database of the Center for International Bone Marrow Transplant Research (CIBMTR). The median age was 47 years (range: 18-73 years). Donors were HLA identical siblings in 162 patients, unrelated individuals in 101 patients, and HLA nonidentical family members in 26 patients. Patients were treated with a variety of conditioning regimens and graft-versus-host disease (GVHD) prophylaxis regimens. Splenectomy was performed in 65 patients prior to transplantation. The 100-day treatment-related mortality was 18% for HLA identical sibling transplants, 35% for unrelated transplants, and 19% for transplants from alternative related donors. Corresponding 5-year overall survival (OS) rates were 37%, 30%, and 40%, respectively. DFS rates were 33%, 27%, and 22%, respectively. DFS for patients receiving reduced-intensity transplants was comparable: 39% for HLA identical sibling donors and 17% for unrelated donors at 3 years. In this large retrospective series, allogeneic transplantation for myelofibrosis resulted in long-term relapse-free survival (RFS) in about one-third of patients. [Copyright &y& Elsevier]