bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cord Blood Transplantation for Adult Acute Lymphoblastic Leukemia.
Authors: Kawano Tomomi , Matsumura Tomoko , Takagi Shinsuke , Kato Daisuke , Yuji Koichiro , Uchida Naoyuki , Masuoka Kazuhiro , Wake Atsushi , Miyakoshi Shigesaburo , Taniguchi Shuichi 
Published: April 2020

Abstract
Backgrounds: Adult acute lymphoblastic leukemia (ALL) has poor prognosis despite intensive chemotherapy. Allogeneic hematopoietic stem cell transplantation is an optimal therapeutic strategy in relapsed ALL patients. HLA-matched unrelated donation is difficult in some cases because of the rapid disease progression. Cord blood transplantation (CBT) excells other measures in its availability, render it particularly effective in urgent situations; however, the outcome of CBT for adult ALL cases has not yet been clarified.
Patients/Methods: We reviewed medical records of 22 adult ALL patients who received CBT at Toranomon Hospital between January 2002 and June 2005. Median age of the patients was 54.5 (range 18–68). Disease status were CR1 (n=4), CR2 (n=3), RL1 (n=8), RL2 (n=1) and primary induction failure (n=6), respectively. 18 patients recieved fludarabine based regimen and the other received CY/TBI myeloablative regimen. Fludarabine based conditioning regimen was consisted of fludarabine (125 mg/m2), melphalan (80–140 mg/m2) and TBI (4–8Gy). GVHD prophylaxis was cyclosporine (n=12) or tacrolimus (n=10). Median total nucleated cell and CD34+ cell counts were 2.6×106 cells/kg (1.6–4.4) and 0.7×105 cells/kg (0.2–3.2), respectively. HLA disparity was 5/6 (n=1), 4/6 (n=20) and 3/6 (n=1).
Results: The probability of disease free survival at 2 years was 59%. Overall survival curves of each conditioning regimen were depicted as below.
Half of the relapsed/refractory ALL patients achieved complete remission and remained disease free after CBT.
Discussion: Adult ALL patients without any suitable donor should be considered as a candidate for CBT.
Figure Figure
Hematopoietic Stem Cell Transplantation (HSCT) for Benign Indications Using Umbilical Cord Blood Units (UCB) That Were Depleted of Plasma, but Not of Red Blood Cells.
Authors: Chow Robert , Jaing Tang-Her , Gjertson David , Rosenthal Joseph , Nademanee Auayporn , Karanes Chatchada , Graham Michael , Tan Patrick , Petz Lawrence D. 
Published: April 2020

Abstract
Background: UCB is an attractive unrelated source for HSCT of benign indications such as hemoglobinapathies, genetic diseases and metabolic disorders, because of less stringent HLA matching requirements, lower incidence and severity of GvHD, and ready availability of a physical inventory; however, unlike BMT or PSCT, cell dosage is a critical factor in success of UCB HSCT. The red cell depletion (RCD) techniques that are widely used by UCB banks incur significant nucleated cell loss after processing. One method of minimizing cell loss during processing is to deplete plasma, but not the red blood cells (PD). A large racially diverse PD UCB inventory of 18,000 units is now available on stem cell registries. We now report our observations of using unrelated PD UCB HSCT for benign indications.
Hypothesis: Usage of unrelated PD UCB for HSCT of benign indications will result in acceptable clinical outcome for myeloid (ANC 500) and platelet engraftment, overall survival (OS), and transplant related mortality (TRM).
Methods: A retrospective analysis was performed on 28 patients with benign disorders who were transplanted with PD UCB in 15 centers and 7 countries, with 13 thalassemias, 5 SAA, 5 WAS, 2 SCID, 1 sickle cell disease, 1 osteopetrosis and 1 metabolic disorder.
Results: The median age of patients was 3.7 years old (range 03–27 years old); median weight 16.0 kg (range 4.5–43 kg); male 57%. Transplant characteristics indicated a median # HLA ABDR matches of 4.0 (5 6/6; 7 5/6; 12 4/6; 3 3/6; 1NA); median pre-freeze TNC dose 7.7 x 107/kg; median post-thaw TNC dose as reported by TC 7.7 x 107/kg; median pre-freeze CD34 dose 3.1 x 105/kg; transplants performed outside of U.S. 68%; double unit transplant 13%; non-myeloablative 6%. The median time to engraftment for ANC 500 (n=21), platelet 20K (n=20), and 50K (n=18) are 14.5 days (range 11–41 days), 47.0 days (range 13–82 days), and 55.0 days (range 21–96 days) respectively. The unadjusted cumulative incidence (C.I.) of ANC500 and platelet 20K and 50K engraftment are 89±7%, 89±7%, and 87±8% respectively. The incidence of reported grade II–IV acute GVHD was 33%, and none had grade III–IV acute GVHD. 50% developed limited chronic GVHD (7/14), and so far only one patient was reported to have extensive chronic GVHD. With a median follow-up of 356 days (range 93–1,100 days), the Kaplan-Meier estimates of 1-year TRM, OS and disease-free survival were 11±6%, 89±6% and 89±6% respectively.
Conclusion: These results demonstrate that HSCT using unrelated PD UCB can be performed safely and effectively in patients with benign disorders. Further study of HSCT using unrelated PD UCB in patients with non-malignant hematological disorders is warranted.
Early Lymphocyte Recovery after Autologous Stem Cell Transplantation Predicts Superior Survival in Mantle Cell Lymphoma.
Authors: Joao Cristina , Porrata Luis F. , Inwards David J. , Ansell Stephen M. , Micallef Ivana N.M. , Johnston Patrick B. , Gastineau Dennis A. , Markovic Svetomir N. 
Published: April 2020

Abstract
Mantle-cell lymphoma (MCL) is characterized by an aggressive clinical course and poor prognosis with a median survival of only 3 to 4 years. High dose chemotherapy followed by autologous stem cell transplantation (ASCT) is an effective treatment strategy for MCL demonstrating significantly prolongs progression free survival (PFS) when compared to IFNa maintenance therapy of patients in first remission. We have previously shown that absolute lymphocyte count at day 15 (ALC-15) after ASCT is an independent prognostic factor for survival in hematologic malignancies (non-Hodgkin’s lymphoma (NHL), Hodgkin’s disease, multiple myeloma, primary amyloidosis, acute myelogenous leukemia) and breast cancer. The study of ALC-15 after ASCT as a prognosis factor in NHL included different subtypes of lymphomas. The relationship of ALC-15 after ASCT in patients with MCL has not been specifically addressed. Herein we present data evaluating the impact of early lymphocyte recovery (ALC-15) in patients undergoing ASCT for MCL. We retrospectively reviewed the medical records of 42 consecutive patients (9 females and 33 males) with MCL who underwent ASCT at the Mayo Clinic in Rochester from 1993 to 2005. Based on our previous studies, the ALC-15 threshold was set at 500 cells/μL. The median patient age at transplant was 57 years (range, 37–71) and the median follow-up after ASCT was 25 months (range, 2–106 months). The median overall (OS) and PFS times were significantly better for the 24 patients that achieved an ALC-15 ≥ 500 cells/mL compared with 18 patients with ALC-15 &lt; 500 cells/μL (not reached versus 30 months, P &lt; 0.01 and not reached versus 16 months, P &lt; 0.0006, respectively). Multivariate analysis adjusting for other prognostic factors suggests that ALC-15 is an independent prognostic factor for OS and PFS. ALC-15 ≥ 500 cells/mL is associated with significantly improved clinical outcomes following ASCT in patients with MCL.
Beneficial Prophylactic Antimicrobial Use Against Infectious Complications during Autologous Stem Cell Transplantation: A Result of Randomized Phase II Study in Multiple Myeloma and Non-Hodgkin’s Lymphoma Patients.
Authors: Kim Shin , Cho Yang Hee , Ko Ock Bae , Koo Ja Eun , Lee Danbi , Chong Young Pill , Suh Cheolwon 
Published: April 2020

Abstract
The benefit of using prophylactic antimicrobials in autologous stem cell transplantation (ASCT) is controversial. A prospective randomized phase II comparison study was therefore performed to assess the benefit of prophylactic antimicrobials. Forty consecutive patients with multiple myeloma (MM, 28 patients) or non-Hodgkin’s lymphoma (NHL, 12 patients) were enrolled. After stratification by disease, patients were randomly allocated into control group with no prophylactic antimicrobials (19 patients) or prophylaxis group receiving prophylactic antimicrobials (21 patients) just before the administration of high-dose chemotherapy. Prophylactic antimicrobials comprised domly allocated into apyylactic lacticiprofloxacin 500 mg po bid, fluconazole 100 mg po bid and acyclovir 200 mg po tid; started one day before high-dose chemotherapy initiation and stopped when absolute neutrophil count reached 500/mm3 after nadir or infection occurred. High-dose chemotherapy was high-dose melphalan for MM and BEAM for NHL. Lenograstim 5 μg/kg/day was given from day 1 of ASCT. At least one episode of fever was present in 15/19 (79%) patients in control group much more frequent than 12/21 (57%) patients in prophylaxis group but with no statistically significance (p=0.13) probably due to small sample size of current study. Microbiologically or clinically documented infections occurred in 4 patients (21%) from control group and in no patient from prophylaxis group, with statistically significant difference (p=0.04). Documented infections of patients from control group included 3 staphylococcal bacteremias (1 methycillin-sensitive Staphylococcus aureus, 1 Staphylococcus epidermidis, 1 Methycillin-resistant coagulase-negative staphylococcus) and 1 herpes skin infection. No death, invasive fungal infection, or serious adverse events occurred in either group. The median duration of fever (12 days in control group and16 days in prophylaxis group), therapeutic antimicrobial therapy (9 days in control group and 11 days in prophylaxis group), and hospital stay after ASCT (19 days in both groups) were not different between groups. Median time to neutrophil engraftment was 10 days and median time to platelet engraftment was 11 days in both groups. In conclusion, this small-sized randomized phase II comparison shows that use of prophylactic antimicrobials as current study diminishes microbiologically or clinically documented infection during ASCT significantly.
Efficacy of Diverse High-Dose Regimens Followed by Autologous Peripheral Blood Stem Cell Transplantation in Consecutive Multiple Myeloma Patients: A Single Center Analysis over a 12 Year Period.
Authors: Haas Peter , Bauchmüller Kris , Kühnemund Alexander , Ihorst Gabriele , Engelhardt Monika 
Published: April 2020

Abstract
Over the last years, high-dose (HD) chemotherapy followed by autologous peripheral blood stem cell transplantation (auto-PBSCT) has emerged as one very effective approach to improve the outcome in multiple myeloma (MM) patients (pts). HD- regimens in MM have been Busulfan and Cyclophosphamide (Bu/Cy) and HD-Melphalan (MEL), with or without total body irradiation (TBI). In this analysis, we analyzed the efficacy of different HD-regimens in consecutive MM (pts) receiving an auto-PBSCT at our institution between 8/1992 and 1/2005. Within these 12.5 years, 120 MM pts (68 male, 52 female) received an auto-PBSCT. Their median age was 56 (27–74) years. According to Durie &Salmon (DS), stage I, II and III disease prior to PBSCT were observed in 5 (4%), 30 (25%) and 85 pts (71%), respectively. Bu/Cy was used until 1997, TBI/MEL between 1997 and 1999, and MEL alone thereafter. The respective HD-regimens consisted of Bu/Cy (Bu 16mg/kg; Cy 120mg/kg) in 15 pts (12.3%), TBI/MEL (10 Gy; MEL 140 mg/m2) in 16 pts (13.1%) and MEL (200mg/m2) in 89 pts (73.0%). The median OS of all MM pts after auto-PBSCT in our analysis was 59.5 months. The therapy related mortality (d0 – d+100 after PBSCT) was 0% (0/15) for Bu/Cy, 3.4% (3/89) for MEL alone and 6.3% (1/16) for TBI/MEL. Main Bu/Cy side effects were infections (n=4), pulmonary fibrosis (n=2), renal failure (n=1) and VOD (n=1). Infections, mostly fever of unknown origin, were observed in the MEL and TBI/MEL group in 68/89 and 15/16 pts, respectively, however in none, pulmonary fibrosis, renal failure or VOD occurred. Comparing Bu/Cy- vs. MEL-conditioning in terms of OS, Bu/Cy prolonged OS in some pts (77.2 vs. 55.6 months, p=0.12), however, this difference failed to be of statistical significance. Our analysis on the influence of TBI on MEL-conditioning revealed no advantage for the combination-therapy (55.6 (+TBI) vs. 59.5 months (−TBI)), which confirms previous studies, also show no benefit for the addition of TBI. In conclusion, our data verify that comparable remission and OS rates can be obtained with less toxic conditioning regimens in MM, such as MEL200 alone, thereby significantly reducing therapy-related side effects. Since auto-PBSCT is an effective treatment option also for elderly and frail MM pts, choosing the best conditioning regimen is important and should improve the treatment outcome in MM further. Current studies are assessing the use of tandem-transplantations and novel anti-MM-agents, such as Bortezomib, Revlimid, Thalidomide and others, before, with and after high-dose regimens. These treatment concepts make highly effective but less toxic conditioning regimens imperative for auto- and allo-transplantations.
High-Dose Sequential Chemotherapy Versus a Less Intensive Chemotherapeutic Regimen Followed by Peripheral Blood Progenitor Cell Autografting in Patients with Advanced Hodgkin’s Disease.
Authors: Nucci Marcio , Urago Katia , Miranda Eliana A. , Delamain Marcia , Souto Filho Joao T. , Matte Silvia F. , Duarte Carla M. , Oliveira Gislaine B. , Vigorito Afonso C. , Pagnano Katia B. , Maiolino Angelo , de Souza Carmino A. 
Published: April 2020

Abstract
High-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) is considered standard of care for patients with Hodgkin’s disease (HD) who relapse or progress after first-line chemotherapy. Recently, high-dose sequential chemotherapy (HDS) before ASCT has been evaluated, and phase II data suggest that it may improve the outcome without increasing significantly the toxicity. However, the lack of comparison between HDS and a more conservative strategy hampers any conclusion about the effectiveness of HDS. In this study, we compared in a non-randomized fashion, HDS (n=52) with a less-intensive chemotherapeutic regimen (non-HDS, n=60) followed by ASCT in patients with relapsed or refractory HD. Patients were treated at 2 Brazilian centers (HDS - UNICAMP; non-HDS - UFRJ). HDS consisted of cyclophosphamide (7 g/m2) followed by stem cell collection, methotrexate (8 g/m2) plus vincristine (1.4 mg/m2) and etoposide (2 g/m2), followed by BEAM and peripheral blood ASCT. Non-HDS patients received 2 cycles of DHAP, followed by cyclophosphamide (1,5 g/m2) followed by stem cell collection, followed by CBV and peripheral blood ASCT. There were more HDS patients with advanced disease (stage IV 40% vs. 13%, p=0.001), bulky disease (62% vs. 39%, p=0.02), and less patients in complete remission (CR) (6% vs. 18%, p=0.04). Toxic death before HSCT occurred in 5 patients in the HDS group and in none in the non-HDS group (p=0.02). Among 31 patients with progressive disease (PD) in the HDS group, 8 (25% remained in PD before ASCT, compared to 100% of 28 patients in the non-HDS group (p&lt;0.001). The actuarial survival from HSCT was similar (58% in both groups, p=0.49), as was the disease free survival (64% in HDS vs. 80% in non-HDS, p=0.19). The outcome of patients from the HDS group who were in PD at the time of HSCT was significantly poorer than patients in CR or partial remission (actuarial survival zero vs. 77%, p&lt;0.001). On the other hand, in the non-HDS group, the overall survival was not influenced by the disease status before ASCT (60% vs. 59%, p=0.77). Although HDS was associated with early deaths, it seemed to be beneficial to patients in PD. These results suggest that HDS could be preferably selected to patients with PD.
Long-Term Safety and Efficacy Data on Childhood Venous Thrombosis Treated with Enoxaparin: An Open Label Survey of Once-Daily Versus Twice-Daily Administration.
Authors: Nowak-Gottl Ulrike , During Christine , Bidlingmaier Christoph , Merkel Nick , Schobess Rosemarie 
Published: April 2020

Abstract
Low molecular weight heparin is as effective as unfractionated heparin for treatment of venous thromboembolism (VT) in adults, and it has been recently demonstrated that once-daily (q24h) or twice-daily (q12h) enoxaparin (E) administration had no impact on safety (bleeding rate) of efficacy (re-thrombosis rate) in the treatment of acute VT. However, in this setting it is still unclear for children, if enoxaparin should be administered q24h or q12h.
In this open label pilot safety study 75 children &gt; the neonatal period, enrolled from two different catchment areas of Germany were treated with E with a target 2–4 h anti Xa activity between 0.4 – 0.8 IU/ml. After the acute thrombotic onset during which E was administered q12h for a median (range) period of 7 (1–14) days, based on the individual decision of the study centres stratification into the study arms once-daily versus twice daily was performed. Enoxaparin was administered in both study centres regardless of age at DVT-onset, thrombus burden, underlying basic diseases or presence of prothrombotic risk factors. No difference was observed between the stratifications performed in the study centres (p=0.5). Median (range) dose administered q24h (n=50) or q12h (n=25) in children with DVT was 1.2 mg/kg (0.5–3.0) respectively. Median (range) treatment duration was 5 months (1–13). Prospectively defined study endpoints were adverse effects, e.g. re-thrombosis, bleeding, and therapy-related death. Median follow-up time was 24 months.
No significant differences were found between the two patient groups treated with respect to anti Xa activities, efficacy and safety. Further statistical analysis performed to evaluate the overall differences between q24h and q12h E administration again revealed no significant differences for the study endpoints: Re-thrombosis occurred in two patients each (p=0.6), and a minor subdural bleeding was diagnosed in one patient treated q12h (p=0.4). During the follow-up no major bleeding or therapy-related death was observed.
In conclusion, data presented here give evidence that long-term enoxaparin administration within the reported target anti Xa activity for treatment of childhood VT has a good efficacy and safety profile when administered q24h. These data have to be confirmed in a multicentre randomised study.
Autologous Transplantation of Non-Cryopreserved Bone Marrow for the Treatment of High-Risk Adult Acute Lymphoblastic Leukemia in First Complete Remission.
Authors: Holowiecki Jerzy , Giebel Sebastian , Krawczyk-Kulis Malgorzata , Sadus-Wojciechowska Maria , Kachel Lucja , Wojnar Jerzy , Stella-Holowiecka Beata , Grosicki Sebastian 
Published: April 2020

Abstract
Autologous hematopoietic stem cell transplantation (HSCT) is a recognised option of post-consolidation therapy for adults with high-risk acute lymphoblastic leukemia (ALL) not having a donor. G-CSF-stimulated peripheral blood SCT results in faster recovery compared to cryopreserved bone marrow transplantation (BMT) and is currentlly used by the majority of centres. In the current study we analyze the feasibility of a new technique of autologous BMT, which does not require cryopreservation. 115 adult patients (median age 24.5 (16–53) years) with high-risk ALL in first complete remission (CR) were treated with autologous BMT between 1991–2004 in a single center using uniform standard operating procedures. Immune phenotype was as follows: proB 17%, preB 9%, common 44%, mature B 1%, preT 9%, mature T 19%. Initial WBC was &gt;30 G/l in 30% of patients. 8% of patients were bcr/abl(+), 38% required &gt;1 course of induction to achieve CR.
Bone marrow was collected in general anaesthesia and further stored for 72 hours in 4degC without any processing and reinfused 24 hours after completion of myeloablative therapy. Conditioning regimen (CAV) consisted of cytarabine 2x1000 mg/m2 d. −3, −2, −1, etoposide 800 mg/m2 d. −3, −2, cyclophosphamide 60 mg/kg d. −3, −2. Median NC dose was 2.0 (0.9–10.8)x10e8, CD34+cell dose − 1.6 (0.4–15)x10e6/kg. Median recovery of ANC&gt;0.5 G/l equaled 16(11–45) days, PLT&gt;50 G/l – 16(10–53) days (11% patients received cytokines to stimulate NC recovery). Median duration of hospital stay since the date of BMT was 19(13–51) days.
The OS rate at 10 years (median follow-up 6.5 years) equaled 57% (+/−5%), LFS rate − 47% (+/−5%). Three patients died within 100 days after ABMT of septic infections (non-relapse mortality rate − 2.6%). None of the analysed factors (age, WBC at diagnosis, immonophenotype, time to achieve CR) was found to influence the long-term outcome.
We conclude that autologous transplantation of non-cryopreserved bone marrow after CAV conditioning is feasible for adults with high-risk ALL. The method is characterized by fast recovery, short hospital stay and low non-relapse mortality, and may constitute good alternative to autologous PBSCT.
In Vivo Purging with Hyper-CVAD Plus Rituximab Followed by Autologous Stem Cells Transplant and Rituximab Maintenance in Newly Diagnosed Mantle Cell Lymphoma: A Pilot Study for GISL (Italian Cooperative Study Group for Lymphoma).
Authors: Benedetti Edoardo , Caracciolo Francesco , Galimberti Sara , Papineschi Federico , Pelosini Matteo , Cervetti Giulia , Castiglioni Maido Gioacchino , Mechelli Sandra , Scatena Paola , Brugiatelli Maura , Petrini Mario 
Published: April 2020

Abstract
Previously untreated mantle cell lymphoma (MCL) are consistently associated with poor prognosis when treated with CHOP-like regimens. Typically the CR rate is 20–30%, median FFS = 10–16 months and median OS = 3 years. In the attempt to improve outcome we used a high dose intensity regimen such as Hyper-CVAD (HCVAD) with autologous stem cell transplant (ASCT). Twenty patients entered the study but only 10 up to now are valuable. Patients were apheresed after 2nd course of HCVAD and if apheresis (LPH) were PCR positive (Bcl1+/JH+) a second set of LPH were performed after completion of 4th cycle. To perform an in vivo purging Rituximab 375 mg/m2 was added at day +1 and +9 after last dose of ARA-C; GCSF 10μg/kg was commenced on day +5 until LPH was ultimated. Rituximab maintenance (375 mg/m2 once weekly for 4 consecutive weeks) started 2 month post-ASCT and was repeated every 6 months. Ten patients have completed 4 HCVAD and 7 /10 underwent ASCT and were conditioned with BEAM. After 4 HCVAD 7/10 patients were in CR and 3/7 in PR. After ASCT 1 PR obtained a CR, 1 PD obtained a VGPR and 5 CR maintained CR. Only 4CR post ASCT have received Rituximab maintenance and maintain CR. Two patients (1 CR blastic variant and 1 PR) refused ASCT and after 4 HCVAD received Rituximab maintenance and both are in CCR. Overall with a median follow up of 28.6 months (range 12–51) median survival is not reached. At 4 years 77.8% of patients are alive and PFS is 87.9%. Patients were monitored for bone marrow-MRD by PCR. Eight out of 10 were PCR+ at diagnosis and 7/8 were PCR negative after 4 HCVAD. After ASCT one PCR+ converted to PCR- and 1 PCR+ patient after 4 HCVAD converted to PCR- with Rituximab maintenance (refused ASCT).
Conclusions: high dose intensity regimen HCVAD + Rituximab as in vivo purging and for maintenance allowed to collect tumor free grafts in 70% of PCR+patients at diagnosis and to reach an ORR of 100%, 7/10 CR and PR 3/10 (included 1 blastic variant). PCR negativity was obtained in 7/8 patients. One patient from PR converted to CR after ASCT and one after Rituximab maintenance (without ASCT); thus we might speculate that both high doses (BEAM) and Rituximab do play a role to increase the probability to obtain a CR and PCR-. Survival and PFS of 77.8% and 87.9% respectively at 4 years are encouraging. Further follow up and a higher enrolment of patients are needed to better define the role of HCVAD + Rituximab and ASCT to increase CR,PCR- PFS and OS in MCL.