bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcome of Relapse after Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) - The Effect of the Underlying Disease on Survival Following Relapse.
Authors: Singhal Seema , Frankfurt Olga , Evens Andrew , Gordon Leo , Tallman Martin , Williams Stephanie , Winter Jane , Grinblatt David , Kaminer Lynne , Mehta Jayesh 
Published: October 2019

We have reported that the outcome of reduced-intensity allogeneic HSCT is not affected by the underlying diagnosis (Mehta et al, ASH 2006). With an additional year’s follow-up and a minimum follow-up of 18 months, this observation continues to remain valid in a series of 91 uniformly-treated patients with hematologic malignancies (19–71 years; median 53; 22% >60 years). 29 patients had acute leukemia, 38 had lymphoma (Hodgkin/NHL) or CLL, and 24 had myeloma. Two-thirds of the patients had refractory disease. Performance status (PS) was 0 in 31%, 1 in 47%, and 2/3 in 22%. Donors (55% aged >45 years) were HLA-matched siblings (n=51), 10/10 allele-matched unrelated individuals (n=29), or 9/10 allele-matched related/unrelated individuals (n=11). The conditioning regimen comprised 100 mg/m2 melphalan with (if no prior autograft) or without (prior autograft) 50 mg/kg cyclophosphamide. GVHD prophylaxis comprised cyclosporine-mycophenolate (HLA-matched sibling donors) or tacrolimus-mycophenolate (other type of donors). G-CSF or GM-CSF were not given routinely to accelerate engraftment. Supportive care was uniform. As the figure shows, the underlying disease did not affect overall survival (OS) after HSCT.
Figure Figure
The underlying disease did not affect disease-free survival, relapse risk or transplant-related mortality. 51 of these patients relapsed. Relapsed disease was treated with immunotherapy (withdrawal of immunosuppression and/or donor cell infusion), and/or non-immune salvage treatment options. The latter included conventional chemotherapy for all 3 disease groups, monoclonal antibodies for NHL, and drugs such as thalidomide, bortezomib and lenalidomide for myeloma. Some patients with poor performance status received only supportive therapy. 43 of the 51 relapsing patients, including all with acute leukemia, died of progressive disease or complications of salvage therapy. The 8 survivors have lymphoma or myeloma, and are in remission or have stable disease. As the figure shows, OS after relapse was significantly affected by the underlying disease.
Figure Figure
Other factors affecting OS significantly after relapse were LDH and performance status. These data suggest that the outcome of patients with hematologic malignancies is generally poor if the disease relapses after reduced-intensity HSCT. However, some patients with lymphoma or myeloma can survive for prolonged periods after relapse because of effective salvage therapy options. Patients with acute leukemia fare poorly because of lack of effective salvage therapy, and exploration of strategies such as a second allograft may be appropriate for them.
Radiation, Mylotarg, and DLI for Extramedullary Relapse from AML Post-Allogeneic Transplant.
Authors: Sharma Manish , Cumpston Aaron , Craig Michael 
Published: October 2019

Abstract
Introduction: Extramedullary relapse of acute leukemia after hematopoietic cell transplant often occurs as granulocytic sarcomas or leukemia cutis. There is no standard of care for these patients and their prognosis is poor. We describe three patients with extramedullary relapse who were treated with a combination of radiation, gemtuzumab ozogamicin and DLI (donor leukocyte infusion).
Methods: All three patients had a diagnosis of AML, underwent induction and consolidation therapy, and then received a myeloablative TBI-based allogeneic transplant. Two patients presented with chloromas and one presented with leukemia cutis as sites of recurrence. None had evidence of bone marrow recurrence, and relapse occurred from 4 – 11 months post transplant. All three were treated with radiation therapy to the site of relapse followed by gemtuzumab ozogamicin and DLI. The radiation doses were 20 – 30 Gy, followed by gemtuzumab ozogamicin 9 mg/m2 given every two weeks for two doses. All three patients received DLI initially at 1.0 x 10-7 CD3+ cells/kg, and subsequently dose-escalated to 2.0 x 10-7.
Results: All three patients achieved complete remission. Median disease free survival has not been reached with a median follow-up of 8 months. One patient with leukemia cutis died from GVHD nine months after the first dose of DLI. The remaining two patients are alive, disease-free, and have no evidence of GVHD.
Conclusion: The combination of radiation, gemtuzumab ozogamicin, and immunotherapy with DLI may offer survival to patients who relapse with AML after allogeneic transplant.
Analysis of Mismatched Umbilical Cord Blood Transplants for Adults Patients 45 Years or Older.
Authors: Lim Seah H. , Esler Willaim V. , Zhang Yana , Zhang Jian , Burris Colleen , Townsend Mary , Periman Phillip O. 
Published: October 2019

Abstract
Although hematopoietic stem cell (HSC) transplants are curative for some patients with hematologic malignancies, they have been applied primarily to younger patients. Yet, hematologic malignancies are commoner in the older populations. Therefore, despite advances in HSC transplants, many patients, especially older patients, still die of their disease. Umbilical cord blood (UCB) transplants have been shown to produce comparable results to those obtained from unrelated bone marrow transplants for adults with hematologic malignancies. UCB transplants may be particularly suitable for older patients needing unrelated HSC transplants since the incidence of GVHD is lower despite the less stringent HLA-matching requirement. Furthermore, UCB procurement is fast and can be accomplished in two weeks. However, data on the applicability of UCB transplants in older adult patient is lacking. The outcome of 14 consecutive adult patients (9 males and 5 females), 45 years or older, needing HSC transplants but without matched sibling donors in a single institution was analyzed. The median age was 55.5 years (range 45–78). The median weight was 72 kg (range 60–105). The median CD34 cells infused were 2.3 x 105/kg. Four patients received one-antigen mismatched, five patients two-antigen mismatched and five patients three-antigen mismatched transplants. Conditioning regimens consisted of Bu/Cy with (n=5) or without (n=1) ATG, Flu/Mel (n=7) and BEAM (n=1). GVHD prophylaxis consisted of cyclosporin A and methylprednisone. Five patients received double UCB transplants. The diagnosis: AML (n =8; 2 untreated secondary AML, 2 primary refractory AML, 2 secondary AML in CR1, 1 secondary AML in CR2 and 1 AML in CR3 and has failed a previous autologous transplant), CML (n=3; 2 in BC and 1 in CP1), CLL (n =2; both with advanced refractory disease) and SAA due to Hep C (n=1). Despite the age of these patients, Grade I–II acute GVHD occured in 10 patients and Grade III–IV in only 2 patients. Three patients died, all from septicemia, before engraftment could be documented. Other deaths include severe GVHD (n=2), VOD (n=1), stroke (n=1), septicemia (n=1) and leukemia relapse (n=1). Five patients are alive and disease-free. As of August 1, 2007, the 5-year actuarial DFS and OS are both 31% for the group and 50% for those <65 years (Figure 1). All five patients >65 years died within 100 days of transplants. In conclusion, some older patients needing HSC transplants may benefit from mismatched UCB transplants if they are not candidates for autologous transplants and do not have HLA-matched siblings. Obviously longer follow-up is needed in these patients to better determine the long-term effect of this approach in older patients. However, further optimization of the conditioning regimen is needed for patients older than 65 years to reduce early TRM due to toxicities.
Figure Figure
Higher CD 34 Cell Doses Reduce Non Relapse Mortality (NRM) and Do Not Increase the Incidence of Graft Versus Host Disease (GVHD) Following Unrelated Donor Blood Stem Cell Transplantation (SCT).
Authors: Narayanan Sujaatha , Barnett Michael J. , Mourad Yasser R. Abou , Forrest Donna L. , Hogge Donna E. , Lavoie Julye C. , Nantel Stephen H. , Shepherd John D. , Song Kevin W. , Sutherland Heather J. , Toze Cynthia L. , Smith Clayton A. , Power Maryse , Nevill Thomas J. 
Published: October 2019

Background: Higher CD34 cell doses have been shown to increase the incidence of acute (Przepiorka D et al, 1999) and extensive chronic GVHD (Zaucha et al, 2001) following HLA-matched sibling SCT. Less is known about the influence of CD 34 cell dose in the unrelated SCT setting.
Methods: A retrospective review was performed involving 81 consecutive adult patients (pts) who underwent unrelated donor G-CSF mobilised blood SCT in Vancouver between June 2000 and October 2006. NRM, relapse risk (RR) and overall survival (OAS) estimates were determined using a Kaplan-Meier technique and univariate and multivariate analyses were done to identify factors predictive of GVHD and outcome, with particular focus on cell dose administered.
Characteristics: There were 46 male and 35 female pts with a median age of 44 (range 17–58) years. Diagnoses included acute leukemia (39 pts), chronic leukemia (14 pts), lymphoma (15 pts) and other (13 pts). Conditioning was TBI-based in 80/81 pts and GVHD prophylaxis was with continuous infusion Cyclosporine and short-course Methotrexate (MTX) (15mg/m2 d +1 and 10mg/m2 d+3, d+6 and d+11). Fifty of 81 pts received >80% of the planned MTX dose. Forty three pts received SCT from a 10/10 high-resolution HLA-matched donor, 25 pts received a 1-antigen mismatched SCT, 12 pts received a 2-antigen mismatched SCT and 1 pt a 3-antigen mismatched SCT. The donor was male for 68 pts and female for 13 pts. Median CD 34 cell dose was 7.75x106 (range−9.46x104–33.6x106)/kg.
Results: The estimated 3-year NRM, RR and OAS were 39% (95%CI 25%–50%), 30% (95%CI 17%–41%) and 43% (95%CI 31%–58%), respectively. In multivariate analysis, CD 34 cell dose >7.75x106/kg was associated with faster neutrophil engraftment, p<0.001 and reduced NRM (28% vs. 49%, p=.019), but did not influence the incidence of either acute or chronic GVHD or OAS. Multivariate analysis showed that the most important predictor of grade 3–4 acute GVHD (49% vs. 22%, p=.005), NRM (65 vs. 30%, p=.006), and OAS (24% vs. 50%) was administration of >80% of the planned MTX dose. Although having a female donor predicted for an increase in NRM (p=.03), it also was associated with a decrease in RR (0/13 pts) and did not affect OAS.
Conclusion: A high CD34 cell dose in unrelated donor blood SCT is desirable in that it does not adversely influence the incidence of GVHD and is associated with faster neutrophil engraftment and a reduction in NRM. Delivery of at least 80% of the planned short-course MTX GVHD prophylaxis continues to be critical in producing a favourable outcome.
Experience with Autologous HSC Transplant in Therapy-Related MDS/AML Using Cells Harvested Prior to the Development of the Secondary Malignancy.
Authors: Costa Luciano J. , Rodriguez Vilmarie , Porrata Luis F. , Lacy Martha Q. , Elliott Michelle A. , Tefferi Ayalew , Lust John A. , Letendre Louis , Colgan Joseph P. , Gertz Morie A. , Gastineau Dennis A. , Litzow Mark R. 
Published: October 2019

Background: Therapy-related MDS/AML (t-MDS/AML) is a common and devastating complication of treatment with alkylating agents and topoisomerase II inhibitors, often employed with curative intent, in standard or high-doses, in the treatment of hematological malignancies and solid tumors. Allogeneic HSC transplant is considered the standard treatment for t-MDS/AML but its applicability is limited by the unavailability of donors, comorbidities in the recipient and risk of acute and chronic graft-versus-host disease. Patients carrying diseases commonly treated with high-dose chemotherapy and autologous HSC transplant (such as multiple myeloma and non-Hodgkin lymphoma) who latter develop t-MDS/AML occasionally have stored HSC harvested prior to the diagnosis of the secondary malignancy (hereafter called early-stored HSC). The benefit of using early-stored HSC to support myeloablative therapy for the treatment t-MDS/AML is unknown.
Methods: Retrospective, single center analysis of patients with t-MDS/AML receiving myeloablative chemotherapy with or without irradiation supported with early-stored HSC.
Results: Six patients received early-stored HSC transplant for treatment of t-MDS/AML between 2000 and 2007. Median age at the time of the transplant was 57 years (range 15–71). Three patients had been primarily diagnosed with follicular lymphoma, 2 with multiple myeloma and 1 with Ewing’s sarcoma. One patient had received prior autologous HSC transplantation. Two patients developed AML, 1 patient CMML, 1 patient RCMD, 1 patient RAEB1 and 1 patient RAEB2. Median time from diagnosis of primary malignancy to HSC harvesting was 26 (2–122) months and from harvesting to development of t-MDS/AML 44 (7–79) months. Conditioning regimen was Cy/TBI in three patients, BuCy in 2 patients and Samarium + Melphalan in one patient. Five patients engrafted neutrophils and 4 patients engrafted platelets 10–34 and 13–126 days after transplant respectively. In 3/6 patients there was disappearance of the pre-transplant chromosomic abnormality (2 patients -7 and 1 patient -7 and t(1;7)). Two patients obtained hematologic CR and two patients obtained CR without full recovery of platelets. One patient died of sepsis 230 days after transplant, one died with refractory disease on day 103 after transplant and one patient is alive with recurrence of t-MDS. Three patients are alive and free of disease 7, 73 and 87 months after transplant.
Conclusion: Myeloablative conditioning followed by autologous, early-stored HSC transplant can provide prolonged survival to patients with tMDS/AML not suitable to allogeneic SCT.
Serial Serum Cytokine Measurement in a Patient with Systemic Scleromyxedema.
Authors: Devos Timothy , Meersseman Wouter , Dubois Benedicte , Goebels Jozef , Verhoef Gregor , Delforge Michel 
Published: October 2019

Abstract
Systemic scleromyxedema (SSME) is a generalized and rare variant of lichen myxedematosus and is characterized by cutaneous papular mucinous deposits and extracutaneous manifestations. In 80% of the cases, SSME is associated with a monoclonal gammopathy and in approximately 10% with multiple myeloma. Pulmonary, gastrointestinal, rheumatologic and severe neurologic complications have been described. Clonal plasma cells are thought to stimulate excessive fibroblast proliferation resulting in the clinical presentation of this disorder, but little is known about the cytokine-mediated crosstalk between the monoclonal plasma cells and fibroblasts. For that purpose, we have sequentially measured the serum levels of the cytokines VEGF, FGF-b, TGF-b1 and IL-6 in a 39-year old male patient diagnosed with SSME and an IgG kappa paraprotein. The patient presented with repeated generalized epileptic insults, cognitive impairment, and progressively developed thickened skin furrows at the level of the glabella. The diagnosis of SSME was histologically proven. A transient neurologic improvement was seen after plasmapheresis and dexamethason pulse therapy and stem cells were subsequently mobilized with the CAD regimen (cyclophosphamide, adriamycin, dexamethason) and readministered after high dose melphalan. The neutropenic phase was complicated by sepsis and progressive neurological deterioration, after which the decision was taken to start with thalidomide at the dose of 200 mg/d. The patient gradually improved and one year later his cognitive function has normalized and the skin lesions have disappeared. A small M-spike remains visible on serum electrophoresis. Levels of VEGF, FGF-b, TGF-b1 and IL-6 were quantified by ELISA on platelet-poor serum and were measured at diagnosis and at six and twelve months after transplantation. Compared to the high pre-treatment levels of all four cytokines, a decrease was observed during the months after transplantation and at six months.
Table 1: serum levels of VEGF, b-FGF, TGF-b1 and IL-6 in a patient with SSME before ASCT 6 months after ASCT one year after ASCT value = mean of 5 serum samples +/− SD VEGF (pg/ml) 227,87 (+/−33,3) 110,81 (+/−24,8) 189,61 (+/−13,5) b-FGF (ng/ml) 17,77 (+/−0,32) 1,93 (+/−0,29) 1,64 (+/−0,37) TGF-b1 (ng/ml) 37,94 (+/−1,21) 20,45 (+/−0,85) 18,95 (+/−0,49) IL-6 (pg/ml) 92,82 (+/−3,2) 33,2 (+/−5,3) 32,0 (+/−4,5)
One year after administration of high-dose melphalan and autologous hematopoietic stem cell transplantation (ASCT), the serum levels of FGF-b, TGF-b1 and IL-6 remain low. Remarkably, since the dose of thalidomide has been tapered because of persistent ulnar neuropathy, the serum concentration of VEGF is increasing but not reaching the pre-transplant levels. We conclude from this report that serum levels of VEGF, FGF-b, TGF-b and IL-6 follow the clinical evolution in this patient with SSME, suggesting a role for these cytokines in the pathogenesis of SSME.
High Dose Sequential (HDS) Followed by Autologous Hematopoietic Stem Cell Transplantation (AHSCT) for Salvage Treatment of Hodgkin’s Disease (HD): A Brazilian Experience.
Authors: Duarte Bruno K.L. , Valente I.S. , Vigorito Afonso C. , Aranha Francisco J.P. , Oliveira Gislaine B. , Miranda Eliana C.M. , Lorand-Metze Irene , Pagnano Katia B.B. , De Souza Carmino A. 
Published: October 2019

Abstract
From May 1998 to November 2006, 77 HD patients who used the regimen of high dose cyclophosphamide HD (CY) 7 or 4g/m2, methotretaxe 8g/m2 and etoposide 2g/m2 followed by AHSCT were analyzed. Their median age was 25.8 (8.8–71.5) years, 46 males and 31 females. At diagnosis 50 (65%) were stage III or IV disease, 10 (13%) had bone marrow involvement, 29 (37.7%) bulky disease and 55 (71.4%) B symptoms. Besides that, all patients were submitted to a mean of 2 (1–4) chemotherapy lives and their status were 3 (3.9%) complete remission (CR), 17 (22.1%) partial remission (PR), 57 (74%) progression disease (PD) or in non-specified sensitivity relapse. Concerning CY dose 30 (39%) received 4 g/m2 and 47 (61%) received 7 g/m2. After the HDCY 16 (20.8%) were in CR, 22 (28.6%) PR, 28 (36.3%) remained in DP and 11 (14.3%) died most in PD. After a median follow-up of 3.97 (1.13–55.9) months, 53 (68.8%) patients were submitted to AHSCT and their present status is 30 alive [18 CR, 2PR and 10 DP]; 23 dead [2 CR, 14PD and 7 related to the procedure]. Overall survival for transplanted patients was 55% in 8 years. Currently we have 33/77 (43%) alive patients, 19 CR, 3 PR, 11 PD. Overall Survival (OS) for whole group was 32%, Disease Free Survival (DFS) 64% and Progression Free Survival (PFS) 40%. Patients who were in DP or relapse prior to the HDCY (57) compared to their status after that had a significant improvement (P=0,001), their OS was 40% to CR-PR group (24) versus 16% PD group (33). In general, mortality was 44 (57%), their cause was 19 PD (43.2%), 8 (18.2%) related to HDCY, 2 (4.5%) related to HDMTX, 7 (16%) related to AHSCT, 6 (13.6%) infections, 1 (2.3%) chronic GVHD after a reduced intensity conditioning regimen transplant and 1 (2.2%) AML. Besides that, 3 patients developed MDS and 1 developed AML. In conclusion, although it had happened a significant number of toxicity related deaths, the sequence is feasible, mainly for sensitive patients and presents an acceptable response. The authors emphasize the high frequency of poor prognosis patients and occurrence of MDS/AML in 4 (5.2%) patients.
Mobilization, Harvesting and Transplantation of Peripheral Blood Stem Cells in Patients with Severe Refractory Systemic Lupus Erythematosus - A Single Center Experience.
Authors: Xiao Yi , Sun Hanyin , Zhou Jianfeng , Liu Wenli , Zhang Yicheng 
Published: October 2019

Abstract
The prognosis for patients with severe refractory systemic lupus erythematosus (SLE) is poor; High dose chemotherapy with hematopoietic stem cell support is a salvage treatment under investigation for these patients. In our center, 17 patients with severe refractory SLE received autologous peripheral blood stem cells transplantation (PBSCT); Peripheral blood stem cells were mobilized with cyclophosphamide 4g/m2 and granulocyte colony-stimulating factor (G-CSF) 5 μg/kg/day. Enough PBSC were collected in all patients. There’s no mobilization-related mortality, while 3 patients developed active lupus after mobilization which was controlled by slightly increasing the dosage of steroids. Following conditioning with cyclophosphamide 6g/m2 plus anti-thymocyte globulin (ATG, 20mg/kg/d, 5 days), cryopreserved PBSC (mean MNC 4.28×108/kg and CD34(+) cell 2.48×106/kg) were infused. Median ANC and platelet engraftment time were days +11 and +12 after transplantation, respectively. Treatment related complications include mucositis (14/17), infection (12/17), liver malfuction (10/17), edema or/and heart failure (3/17), renal failure (2/17), bleeding (5/17); One patient died from cerebral hemorrhage. Median follow-up is 22 months (9–28 months); All the patients improved with the SLEDAI score reduced from 25.2±6.6 before to 9.7±1.2 3 months after transplantation; Steroids were stopped or maintained at very low dose (equal to 5 to 7.5 mg/d predinisone). One patient had overt lupus relapse 8 months following transplant Conclusions Mobilization, harvesting and transplantation of peripheral blood stem cells in patients with severe refractory systemic lupus erythematosus is safe; The short-term result of the approach is effective in this group of patients; More patients needed to enroll a control study to validate the role of high-dose chemotherapy/PBSCT as the salvage treatment for severe SLE.