bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sucessful Management of Pregnancy and Remission-Induction of a Patient with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ALL) by Means of Imatinib Mesilate and HyperCVAD.
Authors: Suzuki Toshiya , Abe Yu , Mori Yuki , Nakagawa Yasunori , Saito Keiko , Matsumoto Yoko , Miyauchi Akito , Sugimoto Mitsuhiro , Suzuki Kenshi 
Published: October 2019

Abstract
A 31-year-old female at 25 weeks and 5days of gestation was referred to the hematology department because of thrombocytopenia. Complete blood cell count was as follows; WBC 3,600/ml(blast 8%), RBC 393x104/ml, Hb11.7g/dl, Hct 34%, and Plt 4.4x104/ml. Bone marrow examination revealed peroxidase negative blasts increased 90% in the marrow. The result of karyotype analysis: 47, XX, t(2;7)(p11.2;p13), ider(9)(q10), t(9;22)(q34;q11), der(22)t(9;22), +der(22)t(9;22) [27/30] ;46, XX[3/30]. FISH analysis showed 88.5% of marrow cells were positive for bcr-abl chimeric DNA. To save mother and baby, we decided to operate cesarean section. A 716-gram healthy female was born at 26 weeks and 2days of gestation age. The day after operation, 600mg/day of imatinib mesilate started. One week after operation, the first course of hyperCVAD chemotherapy dose-reduced to 60% (CPA300mg, VCR 2mg, DOX 50mg, Dex 40g) started with 600mg of imatinib mesilate. Intra-thecal MTX 15mg, Ara-C 40mg, and PSL 20mg injection was given on day 8. Bone marrow was examined on day 21. Marrow blast cells were 0%. Karyotype analysis was normal. FISH analysis showed 2.5% cells had bcr/abl chimeric DNA. Major toxicities of the chemotherapy was not observed. She maintains complete remission until now. She has been treated with second course of modified hyperCVAD(MTX 1,000mg, Ara-C 2,000mg, mPSL 50mg) and is being prepared for unrelated umbilical cord blood stem cell transplantation. The baby grows heathy and no major hematological problems has been observed. Here we report the successful management of pregnancy and remission-induction of a mother with Ph+positive ALL at 25-weeks and 5days of gestation by means of imatinib mesilate and hyperCVAD.
Phase I/II Study of Clofarabine Plus Cyclophosphamide in Adults with Relapsed and Refractory Acute Lymphoblastic Leukemia (ALL).
Authors: Faderl Stefan , Thomas Deborah A. , Gandhi Varsha , Borthakur Gautam , Huang Xuelin , Plunkett William , Burger Jan , Cortes Jorge , O’Brien Susan , Ravandi Farhad , Bretz Jennie , Kwari Monica , Kantarjian Hagop M. 
Published: October 2019

Abstract
Clofarabine (CLO) is a nucleoside analog with activity in pediatric ALL salvage where it has received FDA approval. Less experience with CLO exists in adult ALL. As CLO inhibits DNA repair following exposure to DNA damaging agents, we designed a phase I/II study of the combination of CLO with cyclophosphamide (CY) for therapy of adult patients (pts) with primary refractory or relapsed ALL. Pts with NYHA class ≥ 3 and a cardiac ejection fraction < 45% were excluded. The continual reassessment method (CRM) was applied to determine MTD from 4 dose levels. The starting dose level was CLO 40 mg/m2 i.v. daily x 3d and CY 200 mg/m2 i.v. q12h x 3d. For cohort 2, the dose of CY was increased to 300 mg/m2. Cohorts 3 and 4 maintained these doses with the treatment duration extended to 4 and 5 days, respectively. Additional samples for clinical pharmacology were obtained from consenting pts prior to and following CY on d1 and d2 and prior to CLO on d2.Thirteen pts have been enrolled. Median age was 34 yrs (range 21–72 yrs). Eight pts had pre-B ALL, 2 pts T ALL/LL, 1 pt mature B ALL, and 2 pts biphenotypic acute leukemias. Karyotype was abnormal in 9 pts (no Ph). Median number of prior regimens was 2 (1–6). Two (15%) pts were primary refractory. Median remission duration to initial induction was 11 mos (0–29.8 mos). Three patients were treated in cohort 1 and 10 in cohort 2. Four pts in cohort 2 experienced DLTs (≥ grade 3): elevation of creatinine/renal failure (1), diarrhea (1), transaminase elevations (2), and hyperbilirubinemia (2). Twelve patients were evaluable for response. One pt (70 yrs, prim. refr. pre-B ALL, complex karyotype) of cohort 1 achieved CR after 2 courses, which lasted for 10.3 months. Four pts died on study from infectious complications (days 2, 15, 34, and 41, respectively). Although no MTD has been defined yet and accrual continues in cohort 2, it appears unlikely that the MTD will exceed the dose levels of cohort 2. More information on efficacy will be obtained in the phase II extension part of the study.
Venothromboembolism (VTE) in Patients (pts) with Acute Lymphocytic Leukemia (ALL), Burkitt’s Leukemia/Lymphoma (BL) or Lymphoblastic Lymphoma (LL).
Authors: Vu Khanh D. , Hubbard Julie C. , Lin E. , Faderl Stefan H. , Cortes Jorge E. , O’Brien Susan M. , Kantarjian Hagop M. , Thomas Deborah A. 
Published: October 2019

Abstract
It has been reported that cancer increases the risk of VTE 4-6-fold. The incidence of VTE in cancer pts has been estimated at 1 in 200 per year and has been well documented in solid tumors. Far less is known about the incidence of VTE in pts with hematological malignancies although a recent publication (Blom et al, JAMA293:715, 2005) suggested that pts with hematological malignancies such as lymphoma and multiple myeloma may be at a higher risk of developing VTE than pts with solid tumors. The incidence and risk of VTE has not been well studied in acute leukemias, a population in which prophylaxis is underutilized given the thrombocytopenia associated with intensive chemotherapy. To evaluate the incidence of VTE in pts with hematological malignancies further and to assess the need for VTE prophylaxis, we conducted a retrospective chart review of 299 pts with ALL, BL, or LL who were seen at M.D. Anderson Cancer Center Center from November 1999 to May 2005. Pts received a hyper-CVAD based regimen (fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with methotrexate and high-dose cytarabine). The median observation period was 188 weeks (range 1–328 wks) and included post-consolidation chemotherapy, allogeneic stem cell transplant, and/or salvage chemotherapy. Among 298 evaluable pts, 52 (17%) had confirmed VTE by imaging studies. In 7 pts, VTE was the presenting sign of the malignancy. The median age of pts who developed VTE was significantly higher than of those who did not develop VTE, 48.5 yrs (range 19–75) vs. 42 yrs (range 15–83), respectively (p=0.04). With each year increase in age, the risk of having VTE increased approximately by 1.7% (p=0.059). ALL pts with Philadelphia chromosome (Ph) had a higher incidence of VTE than all other pts (p=0.02), and were 1.8 times more likely to have VTE than non-Ph ALL pts (p=0.007). Caucasian pts or those with history of prior VTE had a significantly higher incidence of VTE (p=0.03 and p=0.002, respectively). The risk was 2 fold higher for Caucasians and 12 fold higher for those with a prior history of VTE. At the time of VTE, platelet counts were below 50 x 109/L in 33%, 50–100 x 109/L in 10%, and greater than 100 x 109/L in 57%. VTE occurs in a significant proportion of pts with ALL, BL, and LL. Thrombocytopenia does not preclude the development of VTE. Older age, Ph positivity, race, and history of prior VTE were significantly associated with the development of VTE. Further analysis of other known risk factors such as the use of erythropoiesis-stimulating agents, hormonal therapy, and other comorbidities is underway to better refine the subpopulation at risk.
Liver Engraftment by Transplanted Human Progenitor Cells with High Aldehyde Dehydrogenase Activity in a Novel Model, NOD/SCID/MPSVII Mice.
Authors: Zhou Ping , Hohm Sara , Hess David A. , Nolta Jan A. 
Published: October 2019

Abstract
Hematopoietic stem cells (HSC) have been reported to generate cells other than the blood lineage and thus hold enormous promise for repairing damaged tissues. Evidence from our lab and others suggests that hepatocytes can be derived from HSC. However, the frequency of HSC-derived hepatocytes varies tremendously among various studies which use different stem cell subsets and different mouse models. Therefore, the significance of hematopoietic stem cell contribution to the repair of liver damage is still controversial. To further explore this potential, we used the beta-glucuronidase (GUSB)-deficient NOD/SCID/MPSVII mouse model for better identification of engrafted human cells. We and others have previously shown that lineage depleted (lin−) human umbilical cord blood-derived cells with high aldehyde dehydrogenase activity (ALDHhi) are enriched for primitive HSC. In the current studies, ALDHhi lin− cells were transplanted into irradiated NOD/SCID/MPSVII mice. One month after transplantation, carbon tetrachloride (CCl4) was administrated into the mice twice a week for 4 weeks to induced liver damage. In this model, ALDHhi lin− cells gave rise to robust hematopoietic reconstitution (71%±13.1 in bone marrow, 12.8%±4% in peripheral blood and 10.7%±8.8% in spleen) while ALDHlolin− cells failed to engraft. In the liver, engraftment of human cells in mice tansplanted with ALDHhi lin− cells was demonstrated by the presence of human Alu DNA using PCR. CD45+ cells were detected by both FACS (2.11%±1.1) and by immunohistological staining in the liver sections. GUSB expression was frequently evident in kuffer cells adjacent to blood vessels and to a lesser extent in the liver parenchyma. GUSB+ cells were more abundant than CD45+ cells. Most interestingly, human liver-specific a-1-antitrypsin mRNA was detected in the recipient murine livers by RT-PCR analysis. Human albumin- expressing cells were also found in these livers, although such cells were rare as compared to human CD45+ or GUSB+ cells. In contrast, human cells were not detected in the livers of mice tansplanted with ALDHlolin− cells in any of our assays. Thus, ALDH-expressing progenitor cells demonstrated potent engraftment of variable cellular phenotypes, suggesting that these adult progenitor cells should be further explored in transplantation models of tissue damage. Our data also support the idea that hematopoietic stem cells may home to the injured liver and release trophic factors that hasten tissue repair, while direct differentiation of these stem cells to hepatocytes or fusion of these cells with hepatocytes is rare and contributes to a lesser extent to liver repair.
Minimal Residual Disease (MRD) after Frontline Therapy in Adolescent and Young Adult (AYA) Patients with Acute Lymphoblastic Leukemia (ALL) Treated on Two Separate Regimens.
Authors: Rytting Michael , Thomas Deborah , Jorgensen Jeffrey , Kantarjian Hagop , Garris Rebecca , Muriera Brenda , O’Brien Susan 
Published: October 2019

Abstract
Retrospective and prospective studies have demonstrated that AYA patients (pts) with ALL have superior outcomes when treated with pediatric rather than adult-type regimens. Pediatric ALL regimens are therefore being applied as frontline therapy for adults up to age 30. Given the relatively favorable outcome for this group and the length of therapy employed, it will be several years before the superiority of this approach can be confirmed. MRD by multiparameter flow cytometry (MFC) might be an early measurement of treatment efficacy, since detection of MRD after initial induction has been shown to predict for decreased disease-free survival (DFS). MRD monitoring may thus provide an early indication of later success for different ALL regimens in AYA patients. MRD was measured by four color MFC using lineage specific antibodies in conjunction with antibodies directed at aberrant antigens. The limit of detection was one cell in ten-thousand. MRD data for 43 pts </= 30 years of age treated with the adult regimen of hyper CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone) with or without rituximab was compared with MRD data obtained from 13 pts treated with the pediatric ABFM regimen. The median age of the two groups was 22 years (range 15–30) and 20 years (range 14–28), respectively. MRD data on day 21 of therapy was available for 33 of 43 pts (77%) treated with hyer-CVAD; 22/33 (67%) were negative, 10/33 (30%) were positive, and one pt had insufficient cells for analysis. On day 90 of therapy, 21 of the 43 pts had data available, and all were MRD negative. All pts treated with the ABFM protocol had MRD assessments performed on day 29 of induction therapy; 8 (62%) were negative, 2 (15%) had suspicious cells in an insufficient sample, and 3 (23%) were positive. Of the 9 pts with MRD measurements on day 84 of therapy, all were negative except for 1 pt who relapsed before day 84. These preliminary data indicate that AYA pts with ALL receiving either hyper-CVAD or ABFM therapy have similar MRD status at the end of induction and after approximately 3 months of consolidation. Given the likely importance of MRD in predicting DFS, this comparison suggests that hyper-CVAD and ABFM may show similar outcomes in this population. Continued accrual and longer follow-up will be required to confirm this hypothesis.
A Case of Peripheral Neuropathy Combined with Leukoencephalopathy after Injection with Intrathecal Methotrexate and Vincristine.
Authors: Lee Hae-sang , Jung Hyun Joo , Park Jun Eun 
Published: October 2019

Abstract
Vincristine and methotrexate are the anchor drugs in the treatment of acute lymphocytic leukemia. The neurological complications caused by either vincristine or methotrexate have been well documented. A 10 year-old girl diagnosed acute lymphocytic leukemia without central nervous involvement and treated with CCG 1882 based therapy. She suffered from ascending paralysis from lower extremities without seizure or mental change three days after the fifth dose of vincristine and the fifth dose of intrathecal methotrexate during consolidation chemotherapy composed of 3-drug(vincristine, methotrexate, and L-asparaginase). Two days later, she developed dysarthria and respiratory discomfort. Her neurological examination showed a symmetric, flaccid, quadriparesis with loss of deep tendon reflex. But, she did not have sensory loss. We thought Guillain-Barre syndrome as first impression and carried out diagnostic evaluation. Viral study revealed no abnormality and cerebrospinal fluid study was not consistent with Guillain-Barre syndrome or infectious disease. Diffusion weighted magnetic resonance imaging showed a well-demarcated area of moderately high signal intensity in the white mater of the both parietal lobes. Neuromuscular conduction test revealed severe amplitude reduction in motor nerve action potential meaning on peripheral polyneuropathy. These findings were corresponded with drug-induced peripheral neuropathy and chemotherapy-related leukoencephalopathy that was detected incidentally. She did not receive further doses of vincristine and intrathecal methotrexate during the consolidation phase. There was gradual improvement of the weakness in the both lower and upper limbs for 3 months. She was recovery to walk with minimal support. We report peripheral neuropathy combined with subclinical leukoencephalopahty after injection with intrathecal methotrexate and vincristine.
Comparison of Different Chemotherapy Regimens in the Management of Acute Myeloid Leukaemia - 5 Years Experience from Pakistan.
Authors: Ullah Khalil , Ahmed Parvez , Raza Shahid , Mahmood Tariq , Khan Badshah 
Published: October 2019

Abstract
OBJECTIVES: This is a retrospective study in acute myeloid leukaemia (AML) patients carried out at Armed Forces Bone Marrow Transplant Centre Rawalpindi Pakistan between July 2001 and June 2006. Aim of the study was to evaluate outcome in AML patients treated with different remission induction and consolidation chemotherapy regimens in our population.
METHODS: During 5 years period between July 2001 to June 2006, 46 patients received treatment for AML at our centre. Twenty nine patients were males and 17 were females. Median age of patients was 21 years (range: 7–56 years). These 46 patients were categorized into two groups on the basis of type of leukaemia and chemotherapy given. In group-I 40 patients (group Ia: 23 patients of M1–M6, less M3 group Ib: 17 patients of AML M3) received anthracycline and cytarabin based chemotherapy. In group- II, six patients (AML- M3) received all trans retinoic acid (ATRA) based chemotherapy.
RESULTS: In group Ia, out of 23 patients, 14 patients (60.8%) achieved complete remission (CR) after remission induction chemotherapy,10 patients remained in CR after 3rd and 4th consolidation. Eleven patients died and five patients relapsed during treatment and follow up. In this group overall CR, relapse rate (RR) and mortality was 30.4% (7/23), 21.7% (5/23) & 48% (11/23) respectively. In group Ib out of 17 patients, 9 patients (53%) achieved CR after remission induction. Eleven patients died during treatment while one patient relapsed in this group. Overall CR, RR & mortality was 29.4% (5/17), 6% (1/17) & 55% (11/17) respectively. In group II all patients achieved CR (100%) after 1st course of chemotherapy. Two of these patients unfortunately died of uncontrolled sepsis during 1st consolidation, while remaining 4 patients 66.6% are on maintenance chemotherapy and are still in CR.
CONCLUSION: Overall CR, RR and mortality in all groups was 35% (16/46), 13% (6/46) and 52% (24/46) respectively at a median follow-up of 36 ± 8 months. Survival in AML-M3 patients treated with ATRA based chemotherapy is significantly superior than anthracycline based chemotherapy (66.6% vs 29.4%). Infection and chemotherapy toxicity being major causes of mortality.
Continuous Infusion of FLAG and Idarubicin for Patients Younger Than 60 Years with Resistant Acute Myeloid Leukemia; a Prospective, Multicenter Phase II Study.
Authors: Kim Hawk , Park Jae-Hoo , Lee Je-Hwan , Lee Jung-Hee , Joo Young-Don , Lee Won-Sik , Bae Sung-Hwa , Ryoo Hun Mo , Lee Kyoo-Hyung ,   Cooperative Study Group A for Hematology
Published: October 2019

Abstract
Continuous infusion (CI) of cytarabine and fludarabine can accentuate drug activities. We studied the feasibility and the efficacy of fludarabine and cytarabin as a continuous infusion plus idarubicin for resistant AML under 60 years old. Inclusion criteria were AML except for acute promyelocytic leukemia, patients with resistant acute myeloid leukemia (failure to achieve CR after initial induction chemotherapy including standard dose cytarabine; early relapse, occurring after a first CR lasting less than 12 months; relapse after allogeneic HSCT; relapses more than 2 times). Induction chemotherapy consists of idarubicin 12 mg/m2 iv infusion over 30 min (day 1–3), fludarabine 30 mg/m2/d and cytarabine 1000 mg/m2/d (day 1–5) as a 24-hour CI. G-CSF was added on day 1–5. Three more cycles of induction chemotherapy except for idarubicin were followed for consolidation. All 29 patients were enrolled. Median age was 40 (18–57). Disease status were primary refractory in 8 (27.6%), early relapse in 19 (65.5%), multiple relapse in 1 (3.4%), and relapse after SCT in 1 (3.4%). Translocation (8;21) and variants (8, 27.6%), and 2 or 3 abnormalities (7, 24.1%) were most common chromosomal abnormalities. Two patients (6.9%) could not complete induction. Twenty three patients had the early evaluation on median day 15 (14–42); median PB blast 0 (0–9.7) % and median bone marrow blast 0 (0–64) %. Median days for hematological recoveries in CR patients were follows: ANC > 500/mm3 (29 days); ANC >1000/mm3 (32 days); platelet >20K/mm3 (31.5 days); platelet>100K/ mm3 (43 days). Response for induction were CR in 8 (27.6%), CRp in 2 (6.9%), and treatment failure in 19 (65.5%, aplasia in 14, indeterminate course in 3, resistant in 2). Median days required for CR was 45 (37–63) days. Consolidation stopped in 9/11: 7 patients underwent SCT; 1 patient died during consolidation; 1 patient stopped due to toxicity; 1 patient due to other cause. Seven patients are alive and two were lost to follow-up. Nineteen patients died of infection (14 patients), toxicity during consolidation (1 patient), relapse after SCT (3 patients) and persistent disease (2 patients). Autolous SCT performed in 2 and allogeneic SCT in 5. Median overall survival in all and CR patients were 2.47 (95% CI 0.83–4.10) and 11.38 (95% CI 1.32–21.44) months, respectively. Relapse occurred after autologous SCT in 2/2 and after allogeneic SCT in 2/5. CI infusion of FLAG plus idarubicin was effective for eradicating blasts with expense of high toxic death. Reduced doses are recommended for CI of FLAG plus idarubicin.
Impact of CRi on the Outcome of Elderly Patients with Acute Myeloid Leukemia.
Authors: Etienne Anne , Charbonnier Aude , Prebet Thomas , Coso Diane , Stoppa Anne-Marie , D’Incan Evelyne , Doglio Marie-Françoise , Sainty Danièle , Mozziconacci Marie-Joelle , Rey Jérome , Gastaut Jean-Albert , Vey Norbert 
Published: October 2019

Abstract
New international recommendations of response for treatment of acute myeloid leukemia (AML) include morphologic complete remission with incomplete blood count recovery (CRi). This response criteria was defined following evaluation of new drugs used for the treatment of AML in first relapse (Sievers et al., JCO2001;19:3244–3254). The objective of our study was to determine the outcome of elderly patients with newly diagnosed AML achieving CRi. Between 1995 and 2006, 240 patients aged 65 years or older with previously untreated acute non promyelocytic leukemia received a conventional anthracycline and cytarabine induction chemotherapy at a single institution. Median age was 71 years (range, 65–85). One hundred and nineteen patients achieved a complete response (CR) (50%), 15 patients achieved CRi (6%), 69 patients had persisting leukemia (29%), and 37 died during remission induction therapy (15%). Patients who reached a CR or CRi after 1 or 2 cycles of induction chemotherapy proceeded to consolidation. Only 9 patients in CRi received this consolidation chemotherapy course (60%) and none had intensification (intermediate-dose cytarabine and/or autologous stem cell transplantation) whereas for patients achieving CR, 88% (n=104) and 69% (n=82) had consolidation and intensification, respectively (p=0,01 and p=0,03). The median overall survival (OS) was respectively 9 and 18 months for patients in CRi and CR (p=0,08). OS was significantly lower for patients in CRi younger than 70 years (5 versus 17 months for CR, p=0,02). By landmark analysis, there was no difference in OS between patients in CRi and a group of 67 patients with induction failure surviving at less 40 days (p=0,14). Disease-free survival (DFS) and remission duration were not significantly different between patients in CRi and CR overall (5 and 8 months, and 5 and 7 months, respectively), but we found a difference for patients younger than 70 years (p=0,004 and p=0,009 for DFS and remission duration, respectively). There was significantly more multilineage dysplasia in patients achieving CRi (8 versus 33, p=0,009) and platelet count at diagnosis were lower (44 G/L versus 82 G/L). Cytogenetic did not differ between the two groups. Our results show that the outcome of elderly patients who achieved CRi is inferior to patients in CR, especially for patients younger than 70 years. Although this response criteria seems to indicate activity, we were not able to found a difference with patients who did not achieve CR. This result will be revaluated in a larger study. Our data also suggest that patients with CRi have different initial disease characteristics.
Figure Figure