bluuebunny/crossref_metadata_2025_split huggingface dataset:
Very Poor Survival of Patients with AML Who Relapse after Achieving a First Complete Remission: The Eastern Cooperative Oncology Group Experience.
Authors: Rowe Jacob M. , Li Xiaochun , Cassileth Peter A. , Appelbaum Frederick R. , Schiffer Charles A. , Wiernik Peter H. , Litzow Mark R. , Cripe Larry D. , Lazarus Hillard M. , Paietta Elisabeth , Dewald Gordon W. , Weinstein Howard J. , Ogden Angela K. , Woods William G. , Shepherd Lois , Feusner James H. , Bloomfield Clara D. , Tallman Martin S. 
Published: April 2020

Abstract
The optimal post-remission therapy for patients in first complete remission (CR1) continues to be debated. Some centers choose to omit more intensive regimens, such as autologous or allogeneic transplantation, preferring to reserve these for treatment after relapse. Such strategies are mostly based on reports of treatment in second CR, but fail to account for the fact that most relapsed patients do not get into a second CR. The purpose of this retrospective study is to analyze the overall survival (OS) rate of AML patients from the date of first relapse. The data are based on the outcome of 2441 patients entered on 8 consecutive ECOG studies for newly diagnosed AML between 1983 and 1997. The studies included are E3483, PC486, E3993, E4995, E1490, E3997 and the two Intergroup studies E3489 and E2491 (INT0129). The data are arbitrarily divided among patients older or younger than 55 years, as this was the age used in most studies to distinguish between younger and older patients. Of 1699 patients ≤55 years, 1150 (68%) achieved CR1 and 402 (35%) relapsed. The median OS of these patients from first relapse was 6.4 months with a 5-year OS of 11%. If APL patients are excluded and the data are analyzed only by studies for young AML patients (less than age 55 or 60), the median OS from first relapse is 6.2 months with a 5-year OS of only 9%. In the US Intergroup Study (E3489) for patients ≤ 55 years, the median OS from first relapse after an allogeneic transplant, an autologous transplant or consolidation chemotherapy was 6.6, 5.2 and 8 months, respectively with a 5-year OS of 18%, 0% and 0%, respectively. The latter data, however, require cautious interpretation as the numbers in these subgroups are small. These data indicate that patients who relapse after standard initial AML therapy have a dismal OS from the time of relapse. Some die at relapse and only a minority achieve a second CR. Those refractory to reinduction therapy uniformly have a very poor prognosis. These data thus suggest that in planning post-remission therapies approaches most likely to lead to a prolonged leukemia-free survival should be offered rather than reserving such strategies following relapse. Survival from relapse.
Survival from relapse AML (incl APL) n No in CR1 No relapsed (%) Median (months) 2-year survival 5-year survival 55 years ≤ 1699 1150 402 (35%) 6.4 18% 11% &gt;55 years 742 362 237 (65%) 4.7 11% 6%
Non-Myeloablative Hematopoietic Transplant with Sirolimus Immunosuppression: Determinants of Outcome.
Authors: Claxton David F. , Wang Chuancai , Carraher Michelle , Ehmann Christopher , Rybka Witold 
Published: April 2020

Abstract
We added Sirolimus to an established conditioning regimen in an attempt to optimize engraftment and anti-tumor effects while minimizing GVHD. 55 patients patients with advanced hematological malignancies (median age 60) received cyclophosphamide (1gm/m2 days −7 and −6) and fludarabine (25mg/m2 days −7 through −3) prior to peripheral blood cell (51 patients) or marrow (4 patients) transplant. All received sirolimus with tacrolimus, both adjusted to 5–15ng/ml, and methotrexate (5mg/m2 days 1,3, 6) immunoprophyllaxis. Tacrolimus was tapered from days 30–45 in matched siblings (Msib -12 patients) and days 40–100 in (most) alternative donor recipients (AltD- unrelated donor or 5/6 matched related cells - 43 patients) without acute GVHD. Median follow-up is 313 days in AltD patients and 337 days for Msib patients. All Msib cells engrafted, whereas 3/43 AltD recipients showed primary graft failure or secondary graft failure (1/43). Msib recipients engrafted more rapidly than those with AltD transplants (p&lt;0.01). For AltD recipients, the CD34 dose had a positive significant effect on donor engraftment - chimerism (p&lt;0.05 for all points up to D100). Median overall and disease free survival was 287 and 230 days respectively for AltD patients and 303 and 167 days for Msib recipients. Amongst AltD patients, 17/43 survive progression free at D114-1167 (median D416), while in MSib patients only 1/12 survives progression free (p=0.0023 ). Two additional patients are disease free after donor lymphocytes (DLI) or withdrawal of immunosuppression in each group. No patient in the Msib group had transplant related mortality (TRM), but in the AltD group there were nine TRMs, including 7 from GVHD (NS). Multivariate analysis showed CD34 dose and donor types had no significant effect on development of progressive disease (PD). However, in general the odds ratio of any PD decreased exponentially as the level of chimerism increased. For example, at D100 the odds of developing PD decreased by 0.699 times when the level of chimerism increased by 0.1. Multinomial logit analysis showed that compared to GVHD death, the odds ratios for PD death decreased exponentially as the level of chimerism increased. In this series of patients with advanced hematological malignancy, Alternative donor cells provided a higher probability of control of disease, albeit with a trend to higher TRM. Higher CD34 cell doses were associated with improved donor engraftment (chimerism) in AltD recipients. For AltD recipients, risk of PD was reduced by increasing donor chimerism, but increasing chimerism is associated with increased risk of death from GVHD. Efforts to improve control of malignancy via more rapid engraftment of donor cells must be tempered with concern regarding potentially severe GVHD.
Figure Figure
Hematopoietic Stem Cell Transplantation (HSCT) as Curative Therapy for Fanconi Anemia (FA) Patients with Acute Leukemia or Advanced Myelodysplasia (MDS).
Authors: Fraser Christopher J. , Wagner John E. , MacMillan Margaret L. 
Published: April 2020

Abstract
Historically outcomes have been very poor for FA patients with advanced MDS or leukemia. It remains controversial as to whether HSCT is indicated for such patients and there is no consensus as to the optimal conditioning regimen in this setting. Traditionally, conditioning for FA patients has incorporated total body irradiation (TBI). Here, we report results of a pilot study in which we have substituted busulfan for TBI, designed for FA patients with one or more high risk features, identified following analysis of 42 previous consecutive URD FA transplants: advanced MDS or leukemia, age &gt;18 years, or previous proven fungal or gram negative infection. Between 12/02–08/04 6 patients were enrolled, 5 with acute leukemia. Patient and disease characteristics are presented in Table 1. Conditioning consisted of busulfan (total 3.2mg/kg), cyclophosphamide (total 40mg/kg), fludarabine (total 140 mg/m2) and ATG (total dose 75mg/kg); GVHD prophylaxis consisted of cyclosporine and mycophenolate mofetil. All patients received prophylactic voriconazole for one month prior to transplant. BM was T cell depleted with CD34 selection by Isolex 300i. Five out of six patients achieved neutrophil engraftment. Median time to an ANC&gt;500 was 16 days (range: 11–20 days). One patient developed Grade I acute GVHD; no patient has developed chronic GVHD. The preparative regimen was well tolerated. Toxicities included Grade IV mucositis (n=1), VOD (n=2), hemorrhagic cystitis (n=1) and CMV pneumonia (n=1). Three patients are alive and in remission with a median follow-up of 575 days.
Table 1 Age Diagnosis FANC group Remission status Donor source D+21 chimerism D+60 chimerism Vital status Patient and disease characteristics 5.9 ALL BRCA2 treated; CR 5/6 related BM 100% donor 100% donor alive d+894 21.7 AML A untreated 5/6 URD BM 99.1% donor 100% donor died resp. failure d+99 20.8 SAA A N/A 5/6 URD BM insufficient cells N/A died VOD d+24 6.6 ALL,MDS,Wilm’s BRCA2 ALL treated CR; MDS (7.5% blasts) 6/6 URD UCB 100% donor 100% donor alive d+575 7.1 AML A treated; refractory 4/6 UCB + 5/6 UCB 100% donor #2 54.7% #2; 45.3% recipient died AML relapse d+60 17.3 AML A treated; refractory 5/6 UCB x2 66.7% #1; 31.3% #2; 2% recipient 100% donor #1 alive d+423
These results suggest TBI is not required to achieve durable engraftment and leukemia control, busulfan 3.2 mg/kg is tolerable, and advanced MDS or acute leukemia does not preclude HSCT in FA patients.
High-Dose Melphalan and Autologous Stem Cell Transplantation in Unusual Non-Amyloid Light Chain Deposition Disorders.
Authors: Weichman Karin I. , Seldin David C. , Quillen Karen , Rosenzweig Michael , Dember Laura M. , Skinner Martha , Wright Daniel G. , Sanchorawala Vaishali 
Published: April 2020

Abstract
Light chain deposition disease (LCDD) is caused by a clonal plasma cell disorder in which fragments of monoclonal immunoglobulin light chains, usually with a kappa genotype, are deposited in various tissues in a globular form resulting in organ dysfunction. Crystal-storing histiocytosis (CSH) is another light chain deposition disorder in which monoclonal light chains form intracytoplasmic crystalline deposits. Both LCDD and CSH are uncommon diseases, for which there is limited treatment experience. However, conventional anti-plasma cell chemotherapy with oral melphalan as is used in multiple myeloma has been tried in LCDD with little benefit. Between 1999–2005, five patients with LCDD and one patient with CSH have been treated at Boston University Medical Center with high-dose intravenous melphalan (IVM) followed by autologous peripheral blood stem cell transplantation (SCT). Patients have been treated with either 200mg/m2 of IVM (n=5) or 140 mg/m2 (n=1) depending on age and clinical status and subsequently have been assessed for hematologic responses and for improvements in organ function at 3, 6 and 12 months, and annually thereafter. The median age of patients at the time of treatment has been 45 years (range 34–51). Four patients with LCDD had kappa light chain deposition involving the kidneys and 1 of these patients had extrarenal involvement of the heart on electron microscopy of endomyocardial biopsy as well. One patient with LCDD had lambda deposition involving kidneys only. The patient with CSH had only renal involvement, with kappa light chain plasma cell dyscrasia. All except 1 patient had impaired renal function with creatinine clearance ranging from 21 – 64 ml/min. All treated patients are alive and well at a median follow up of 13.6 months (range 5–24 months). Median survival has not yet been reached. No treatment-related deaths were noted, and treatment-related toxicities were manageable and reversible. All evaluable patients (n=4) have achieved a hematologic complete response of the underlying plasma cell dyscrasia after IVM/SCT. In conclusion, this experience indicates that IVM/SCT is a safe, feasible, and effective modality for the treatment of these unusual light chain deposition disorders.
Intramyocardial Injection of CD133+ Bone Marrow-Derived Stem Cells Improves Cardiac Function Long-Term in the Majority of Selected Patients with End-Stage Ischemic Heart Disease.
Authors: Stockschlaeder Marcus A. , Ghodsizad Ali , Stoldt Volker , Poll Ludger , Scharf Ruediger E. , Gams Emmeran , Klein Michael 
Published: April 2020

Abstract
To improve tissue regeneration of ischemic myocardium, autologous bone marrow-derived stem cells have been injected intramyocardially in 10 patients with end-stage ischemic heart disease. Approx. 60 – 380 ml of bone marrow were harvested from the posterior iliac crest and processed in the operating room under GMP conditions using the automated cell selection device CliniMACS. By using the Duesseldorf protocol, the intraoperative isolation of CD133+-stem cells (1.9−10.0 x 106 cells; purity up to 97%) was achieved in less than 3 hours. Following isolation, autologous CD133+-stem cells were injected in a predefined pattern into the myocardium. Cardiac function was assessed by cardiac MRI and echocardiography three, six, and nine months postoperatively. A significant improvement of cardiac function could be documented in 7 out of 10 patients: ejection fraction (EF) before treatment: 10–22% - after 3 months: 18–30% - after 6 months: 19–30%, after 9 months: 21–31%; left ventricular enddiastolic volume (LVEDV) before treatment: 210 ± 123 ml, after 3 months: 169 ± 80 ml, after 6 months: 162 ± 82 ml, after 9 months: 175 ± 70 ml; left ventricular enddiastolic diameter (LVEDD) before treatment: 79.2 ± 7 mm, after 3 months: 57.4 ± 3 mm, after 6 months: 59.4 ± 4 mm, after 9 months: 56.2 ± 5 mm, respectively. In two patients cardiac function improved only temporarily over the first three months, 1 patient died one month after surgery due to a non-cardiac cause. In conclusion, the sole intramyocardial injection of autologous CD133+-cells proved to be safe and led to a significant gain in heart function in 7 of 10 patients, thereby avoiding or postponing (“bridging”) alternative therapies such as heart transplantaton. The benefial effects of intramyocardially injected bone marrow-derived stem cells might be explained by direcct cellular effects including neovascularization and indirect effects including the formation of growth factors promoting tissue repair.
Outcome of Upfront Autologous Peripheral Blood Stem Cell Transplantation for Multiple Myeloma in African American Versus Non Non-African American Patients.
Authors: Khaled Yasser , Kamboj Ginny , Donthireddy Vijaya , Hnaide Hazem , Oja-Tebbe Nancy , Divine George , Janakiraman Nalini 
Published: April 2020

Abstract
Introduction:
Blacks in the United States are twice as likely to suffer from multiple myeloma as whites. Among African Americans, myeloma is one of the top 10 leading causes of cancer death. Although Multiple Myeloma seems to be more aggressive in African Americans, it is not known if they have worse outcome after autologous peripheral blood stem cell transplantation in comparison to Non African American.
Method:
We performed a retrospective analysis of 86 consecutive patients with Multiple Myeloma who underwent autologous peripheral blood stem cell transplantation between July 1991 and November 2004. Thirty two Patients were African American (37.21%) and fifty four patients were Non-African American (62.79%.). Conditioning regimen was Melphalan-200 in 57 patients and Melphalan140/TBI in 29 patients. No significant statistical differences were observed between African Americans and non African Americans prior to the transplant regarding gender, regimen used, immunoglobulin subtype, cytogenetics, stage, or disease status on univariate analysis.
Results:
There was no significant statistical difference in overall survival or event free survival between African American and non African American. However African American were observed to relapse significantly earlier than non African- American (p=0.0274). Despite the early relapse in African American, survival after relapse was longer for African American compared to non African American (p=0.060), however this result was only marginally significant.
Conclusion:
In this single institution experience, there was no difference in the OS or DFS after upfront autologous peripheral blood stem cell transplantation for Multiple Myeloma in African American and non- African American patients. Although time to progression was significantly shorter in African American versus non African American, surprisingly this was not associated with shorter survival. Despite that these results are limited by the sample size; they are intriguing and need further testing in larger group of patients.
Autologous Peripheral Stem Cell Transplantation(ASCT) for Refractory or Recurrent Hodgkin Lymphoma.
Authors: Koike Mitsuru , Kato Masayuki , Kato Yo , Saito Tasuku , Takimoto Madoka , Irei Michiko , Inoue Yasuyuki , Shibuya Yasushi , Koike Junki , Suzuki Takao , Takahashi Masatomo 
Published: April 2020

Abstract
We performed retrospective analysis of ASCT with high-dose therapy consisting of etoposide and cyclophosphamide with cytosine arabinoside or carboplatinum in 11 pts with primary refractory or recurrent Hodgkin lymphoma.
Pts and method: The patients were treated by ASCT from December 1992 to July 2005 in the hospital. Pts characteristics at initial diagnosis were male 4, female 7, and median age 40 year-old (range 33–40) at initial diagnosis. Histological types were NS: 7, MC: 2 and LP: 2. Clinical stages were 2A:3, 3A: 1, 3B: 3, 4A:2 and 4B: 2. Disease status at ASCT was 1st PR: 8 and 1st recurrence: 2 and 2nd recurrence: 1. Two of 11 pts had a history of prior radiotherapy. Peripheral blood stem cell harvesting was performed followed by late phase of initial chemotherapy or high dose etoposide for salvage therapy with granulocyte stimulating factor. All pts were restaged at 1 month or more after transplantation to evaluate the response to the high dose chemotherapy itself. The response to radiotherapy following ASCT was evaluated 2 months after completion of radiotherapy.
Results: Response to high dose chemotherapy was CR 6 pts and PR 5 pts. Five PR pts were treated with radiation and achieved CR. Cumulative response rate in high-dose chemotherapy with/without radiotherapy was 100%. Median follow-up period was 119 months (range 14–145). No recurrent case was observed. However one of these patients had inexplicable cardiac arrest at 100 months after ASCT. Although the patient survived, it was necessary for her to be in hospital by reason of severe anoxic encephalopathy.
Discussion: ASCT for Hodgkin’s lymphoma seems to be feasible salvage therapy in intractable case. However high-dose chemotherapy alone was poor potential to be cure in our limited experience. If high-dose chemotherapy induces PR, radiotherapy should be scheduled based on careful therapeutic response evaluation of high-dose chemotherapy.
Successful PBSC Mobilization, Collection, Transplantation and Engraftment after Radioimmunotherapy with Yttrium-90 Ibritumomab Tiuxetan for Non-Hodgkin’s Lymphoma (NHL).
Authors: Ely Pamela , Stearns Diane M. , Zaki Bassem I. , Fitzmaurice Thomas F. , Gautier Marc , Lowrey Christopher H. , Bengtson Elizabeth M. , Hill John M. , Schaal Anna D. , Kimtis Elizabeth A. , Root Lynn , Webber Susan , Szczepiorkowski Zbigniew M. , Meehan Kenneth R. 
Published: April 2020

Abstract
Radioimmunotherapy (RIT) is a useful addition to the armamentarium against NHL. Due to concerns about chronic myelosuppression and the possible inability to mobilize stem cells or tolerate further therapy after RIT, this modality has not been commonly utilized in potential transplant candidates. We report the successful mobilization, collection, transplantation and engraftment of 5 patients with NHL following yttrium-90 ibritumomab tiuxetan. Patients had follicular lymphoma, grade I or II (n=3), transformed follicular lymphoma (n=1) or blastic variant mantle cell lymphoma (n=1). Time from RIT to mobilization was 10 months (median; range 7–27 months). The median number of regimens prior to RIT was 2.5 (range 1–4) including prior autologous transplant (n=1). The median number of regimens following RIT and prior to transplant was 1.5 (range 1–2). All patients exhibited chemosensitive disease. Patients were mobilized with R-ICE/G-CSF (n=4) or G-CSF alone (n=1) and required 2.8 leukaphereses (mean; range 2–5). The CD34 yield was 3.8x106 CD34+ cells/kg (median; range 3.4–5.1x106 CD34+ cells/kg). All patients received busulfan, VP-16, ARA-C and cyclophosphamide (BVAC) as the preparatory regimen. One patient received IL-2 from day 0 to day 11. Time to engraftment was 13 days (median; range 9–19 days) for an absolute neutrophil count (ANC) &gt;500 cells/ml and 23 days (median; range 15–44 days) for a platelet count&gt;20x103/ml. The patient on the IL-2 study showed delayed engraftment of both ANC (day 19) and platelets (day 27). The patient with mantle cell lymphoma, who was undergoing his second autologous transplant, exhibited delayed platelet engraftment (day 44). Time to engraftment did not differ significantly for either ANC (p=0.16) or platelets (p=0.10) in 18 RIT-naïve NHL patients receiving BVAC and an autologous peripheral blood stem cell transplant (PBSC) during the same time period. There were no treatment-related deaths. With a median follow up of 12 months, one patient has died of disease recurrence. Two patients remain in complete remission. Two patients are alive with disease (relapse at 12 months and 14 months) and are currently receiving therapy. No patient has demonstrated laboratory or cytogenetic evidence of a myelodysplastic syndrome. In conclusion, heavily pretreated patients who have received radioimmunotherapy with yttrium-90 ibritumomab tiuxetan and subsequently relapse can successfully undergo mobilization, collection, and autologous PBSC transplant. These patients demonstrate full engraftment, durable remissions and tolerate additional therapy should relapse occur following transplant.
Long-Term Renal Outcome of Autologous Stem Cell Transplantation in Light Chain Deposition Disease.
Authors: Lorenz Elizabeth C. , Gertz Morie A. , Fervenza Fernando C. , Leung Nelson 
Published: April 2020

Abstract
Light chain deposition disease (LCDD) is a systemic disorder characterized by deposition of nonamyloid monotypic light chains throughout the body. Renal dysfunction is a ubiquitous manifestation of the disease. Reports suggest that high-dose chemotherapy and autologous stem cell transplantation may be beneficial in the treatment of LCDD. However, the impact of autologous stem cell transplantation on renal function is unclear. This study retrospectively reviewed the effect of autologous stem cell transplantation on renal function in six patients with LCDD. Two patients had concurrent multiple myeloma, and one patient was on hemodialysis prior to transplantation. Patients received chemotherapy with dexamethasone alone or dexamethasone plus thalidomide prior to transplantation. Conditioning was performed with high-dose intravenous melphalan. All patients survived transplantation, but one sustained multi-organ failure shortly afterwards and died. Another patient required temporary hemodialysis following transplantation. All surviving patients achieved a hematologic response, although one ultimately relapsed and required further chemotherapy. Renal parameters also improved. On average, proteinuria levels decreased by 83% in four patients and increased by 1% in one patient. Creatine clearance calculated by the Modification of Diet in Renal Disease (MDRD) Study prediction equation improved by an average of 40%. This review suggests that autologous stem cell transplantation may be an effective therapy for renal dysfunction associated with LCDD.
Clinical Characteristics of LCDD Patients at Presentation Characteristic Number or range Median *Modification of Diet in Renal Disease Study prediction equation Sex 4 male, 2 female Age (years) 35-61 44 Beta-2 microglobulin, μ/ml 3.58-11 4.12 Albumin, g/dl 1.8-4.2 3.85 Creatinine, mg/dl 1.8-5.4 2.45 MDRD*, ml/min 12-50 26.5 Serum M protein, g/dl 0 0 Serum free light chains, mg/dl (n = 5) 2.18-312 19.6 24-hour urine protein, mg 131-10,251 679