scholarly journals Lymphoblastic lymphoma in adults: results of a pilot protocol

Blood ◽  
1981 ◽  
Vol 57 (4) ◽  
pp. 679-684 ◽  
Author(s):  
CN Coleman ◽  
JR Cohen ◽  
JS Burke ◽  
SA Rosenberg
Keyword(s):  
Lymphoblastic Leukemia ◽  
Abdominal Mass ◽  
Lymphoblastic Lymphoma ◽  
Myelogenous Leukemia ◽  
High Dose ◽  
Actuarial Survival ◽  
Female Ratio ◽  
Cns Disease ◽  
Cns Relapse ◽  
Male Female Ratio

Abstract Thirteen adult patients with histologically confirmed lymphoblastic lymphoma were treated with an intensive chemotherapy program consisting of induction with cyclophosphamide, adriamycin, vincristine, and prednisone (modified CHOP); consolidation and central nervous system (CNS) prophylaxis with methotrexate intrathecally and by high-dose intravenous injection, citrovorum factor and L-asparaginase; reinforcement with CHOP; and maintenance with 6-mercaptopurine and methotrexate. Treatment duration was 1 yr. A 14th patient with T-cell acute lymphoblastic leukemia was also treated at presentation by the same regimen. Thirteen patients had at least a mediastinal mass or abnormal cells in the bone marrow; one presented with CNS disease. The median age was 22 yr (range 16--50), and male--female ratio was 2.5:1. All patients had a rapid complete clinical response. Of the 13 patients without initial CNS disease, 4 have relapsed, 3 with primary CNS relapse and 1 with a recurrent abdominal mass. Five patients have died, 2 from drug toxicity, 2 from CNS relapse, and 1 from chronic myelogenous leukemia, which was diagnosed simultaneously with the lymphoblastic lymphoma. The median follow-up is 19 mo, and all patients have completed their planned therapy. At 3 yr, the actuarial survival is 61% and relapse-free survival is 56%.

scholarly journals Lymphoblastic lymphoma in adults: results of a pilot protocol

Blood ◽  
1981 ◽  
Vol 57 (4) ◽  
pp. 679-684
Author(s):  
CN Coleman ◽  
JR Cohen ◽  
JS Burke ◽  
SA Rosenberg
Keyword(s):  
Lymphoblastic Leukemia ◽  
Abdominal Mass ◽  
Lymphoblastic Lymphoma ◽  
Myelogenous Leukemia ◽  
High Dose ◽  
Actuarial Survival ◽  
Female Ratio ◽  
Cns Disease ◽  
Cns Relapse ◽  
Male Female Ratio

Thirteen adult patients with histologically confirmed lymphoblastic lymphoma were treated with an intensive chemotherapy program consisting of induction with cyclophosphamide, adriamycin, vincristine, and prednisone (modified CHOP); consolidation and central nervous system (CNS) prophylaxis with methotrexate intrathecally and by high-dose intravenous injection, citrovorum factor and L-asparaginase; reinforcement with CHOP; and maintenance with 6-mercaptopurine and methotrexate. Treatment duration was 1 yr. A 14th patient with T-cell acute lymphoblastic leukemia was also treated at presentation by the same regimen. Thirteen patients had at least a mediastinal mass or abnormal cells in the bone marrow; one presented with CNS disease. The median age was 22 yr (range 16--50), and male--female ratio was 2.5:1. All patients had a rapid complete clinical response. Of the 13 patients without initial CNS disease, 4 have relapsed, 3 with primary CNS relapse and 1 with a recurrent abdominal mass. Five patients have died, 2 from drug toxicity, 2 from CNS relapse, and 1 from chronic myelogenous leukemia, which was diagnosed simultaneously with the lymphoblastic lymphoma. The median follow-up is 19 mo, and all patients have completed their planned therapy. At 3 yr, the actuarial survival is 61% and relapse-free survival is 56%.

scholarly journals Immunophenotypic study of acute leukemia by flow cytometry at BPKMCH.

2013 ◽  
Vol 3 (5) ◽  
pp. 345-350
Author(s):  
S Shrestha ◽  
J Shrestha ◽  
CB Pun ◽  
T Pathak ◽  
S Bastola ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Acute Leukemia ◽  
Acute Myelogenous Leukemia ◽  
Lymphoblastic Leukemia ◽  
Bone Marrow Examination ◽  
Myelogenous Leukemia ◽  
Female Ratio ◽  
Flow Cytometric ◽  
Male Female Ratio ◽  
Acute Myelogenous

Background: Immunophenotyping of acute leukemia is one of the most important clinical applications of fl ow cytometry. The aim of this study was to determine the immunophenotyping profi le of acute leukemia, by means of a fl ow cytometric method, using monoclonal antibodies all marked with a fl uorochrome, in four colour systems to assess their distribution according to type of leukemia (lymphoid B or T / myeloid). Materials and Methods: We retrospectively collected data of immunophenotyping from 52 acute leukemia patients at the department of pathology in B.P. Koirala Memorial Cancer Hospital from January 2010 to December 2011. Diagnosis was based on peripheral blood and bone marrow examination for morphology, cytochemistry and immunophenotypic studies. Results: Out of total 52 cases of acute leukemia diagnosed by fl ow cytometry over a two year period, there were 31 cases (59.6 %) of acute lymphoblastic leukemia, 20 cases (38.4 %) of acute myelogenous leukemia and one case (1.9 %) of bi-phenotypic acute leukemia. Leukemia was diagnosed among adults in 44.2 % whereas among children with age less than or equal to 15 years in 55.7 %. Thirty eight (73%) were male and 14 (27 %) were female with a male: female ratio of 2.7:1. For acute myelogenous leukemia, it was found that M0 (5.0 %), M1 (20%), M2 (60%), M3 (15%), M4 (5.0 %) were detected. CD13 and CD33 were the most useful markers in the diagnosis of acute myelogenous leukemia. The most common subtype was AML-M2. Of the 31 cases with acute lymphoblastic leukemia, 20 cases (64.5 %) were identifi ed as B-ALL and 11 cases (35.5%) as T-ALL. Aside from cytoplasmic CD3 (cCD3) and CD7 were the most sensitive antigens present in all cases of T-ALL. All cases of B-ALL showed expression of pan B-cell markers CD19 and CD22, but 15 (75 %) of 20 cases expressed CD10. Conclusion: Flow cytometric immunophenotyping was found to be especially useful in the correct identifi cation and diagnosis of acute myeloid or lymphoblastic leukemia and its subtypes. In combination with French-American-British (FAB) morphology and immunophenotyping, we were able to diagnose and classify all patients with acute leukemia in this study. Journal of Pathology of Nepal (2013) Vol. 3, No.1, Issue 5, 345-350 DOI: http://dx.doi.org/10.3126/jpn.v3i5.7856

High-Dose Methotrexate and Early Intensification of Therapy Do Not Improve 3 Year EFS in Children and Adolescents with Disseminated Lymphoblastic Lymphoma. Results of the Randomized Arms of COG A5971

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3610-3610 ◽  
Author(s):  
Minnie Abromowitch ◽  
Amanda Termuhlen ◽  
Myron Chang ◽  
Sherrie L. Perkins ◽  
Thomas Gross ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lymphoblastic Leukemia ◽  
Bone Marrow Involvement ◽  
Disease Free Survival ◽  
Lymphoblastic Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Cns Disease ◽  
Dose Methotrexate ◽  
Significant Difference

Abstract The treatment of pediatric lymphoblastic lymphoma (LL) has developed in parallel with treatment strategies for childhood acute lymphoblastic leukemia using a BFM backbone. The excellent results of the NHL/BFM 90 trial prompted us to design this randomized factorial study to determine whether a regimen without high dose methotrexate (HDMTX) the CCG BFM will result in the same outcome as NHL/BFM-90 and whether intensification with anthracycline and cyclophosphamide would further improve disease free survival. From June 2000 to October 2005, 257 patients with Murphy’s Stage III and IV (excluding CNS disease) LL were randomized to one of the four regimens. All regimens used the BFM/NHL95 backbone. The CCG BFM regimen had intrathecal (IT) methotrexate throughout interim maintenance and maintenance without IV methotrexate. The NHL BFM utilized I.V. Methotrexate 5 Gms/m2 and intrathecal MTX every 2 weeks for four doses during interim maintenance without further intrathecal MTX during maintenance. One of each backbone regimens was further intensified with anthracycline and cyclophosphamide early in induction and delayed intensification. The median age was 10.3 years, 195 (76%) were males; 43 (17%) had >5% bone marrow involvement. Twelve patients with CNS disease were not randomized and received intensification and HD HDMTX with delayed CNS radiation (data not reported here). Major toxicities have been related to bone marrow suppression with 4 toxic deaths, 3 due to sepsis and 1 from cerebral hemorrhage. The frequency of grade III/IV neutropenia (alone, with fever or with infection), anemia, and thrombocytopenia were higher in the intensified arms during induction. Three of the four toxic deaths occurred on the intensified arms. The three years EFS of the HDMTX vs. none is 84.5% ± .3.5% vs. 82.7± 3.8 (ρ= 0.93) and the intensification vs. none is 83.4% ±3.7 vs 83.0% ± 3.6 (ρ= 0.66). Therefore, there was no significant difference between treatment arms. These results suggest that neither HDMTX nor early intensification improves EFS in LL. Future direction should focus on identifying biological factors early in therapy so alternative therapies may be investigated.

Liposomal Cytarabine (DepoCyte®) for the Prophylaxis and Treatment of Central Nervous System Involvement In Adult Acute Lymphoblastic Leukemia (ALL) - A Retrospective Analysis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2122-2122
Author(s):  
Beata Piatkowska-Jakubas ◽  
Wojciech Jurczak ◽  
Sebastian Giebel ◽  
Aleksandra Holowiecka-Goral ◽  
Maria Adamczyk-Cioch ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Systemic Chemotherapy ◽  
Lymphoblastic Leukemia ◽  
Central Nervous System Involvement ◽  
Concomitant Administration ◽  
Liposomal Cytarabine ◽  
Female Ratio ◽  
Cns Relapse ◽  
Male Female Ratio

Abstract Abstract 2122 Background: Central nervous system involvement in Acute Lymphoblastic Leukemia can be either primary, present at diagnosis or associated with relapse of the disease. Prevention and treatment of CNS relapse is an essential component of all ALL chemotherapy regimens. Liposomal cytarabine (DepoCyte) is a sustained release formulation of Ara-C with a homogeneous distribution throughout the neuroaxis and a prolonged half-life maintaining cytotoxic concentrations in the CSF for more than 14 days. DepoCyte obtained superior response rates, improved patient quality of life and improved the time to neurological progression compared to standard cytarabine in a randomized clinical trial (Glantz et al 1999). Materials and Methods: A retrospective analysis was carried out to evaluate feasibility, safety and efficacy of DepoCyte in the prophylaxis and treatment of ALL patients. 45 patients who received 50mg liposomal cytarabine either as a prophylaxis (N=24) or treatment (N=21) between March 2006 – December 2009 in 4 centers in Poland were included in the analysis. Baseline characteristics of patients who completed CNS prophylaxis with DepoCyte: median age 34 (range: 18–67 years), male/female ratio 16/8, B-cell ALL (n=17), T-cell ALL (n=4), Ph-positive ALL (n=3). In the treatment group median age was 35 (range 18–60), male/female ratio 12/9, B-cell ALL (n=15), T-cell ALL (n=3) and Ph-positive ALL (n=3). Results: In the prophylaxis group the average number of DepoCyte administrations was 2.6 (range 2–4). Oral or IV Dexamethasone for 5 days was given to all patients to prevent symptoms of arachnoiditis. With a median follow-up of 12 months (range: 3–27) only 1 pt developed combined systemic and CNS relapse. 25% of patients (6/24) experienced mild and transitory adverse events: headache (n=3), brain edema during methotrexate-containing consolidation (n=1) and post-puncture syndrome (n=2). In the treatment group 8 pts were in first isolated CNS relapse and 13 pts were in combined CNS and systemic relapse. All patients had neurological symptoms and blast cells identified in the cerebrospinal fluid with average cellularity 713/μL (range 20–2500/μL). In 2 patients CNS disease was confirmed by computed tomography. DepoCyte was administered intrathecally together with systemic chemotherapy in 18 patients. The treatment was planned to avoid concomitant administration of DepoCyte and other cytotoxic agents that cross the BBB. All patients received concurrent dexamethasone for prophylaxis of arachnoiditis. Neurological and cytological responses were obtained in all 21 pts (16 CRs and 5 PRs). No serious adverse events with DepoCyte were reported. Mild headache was the most commonly reported toxicity (10/21pts, 47.6%). 2 out of 21 (9.5%) heavily pretreated patients developed transient sacral radiculopathy. Conclusions: 1) Implementation of liposomal cytarabine as IT prophylaxis in ALL patients reduces the total number of IT injections, is feasible and effective and has a favorable tolerance profile. 2) DepoCyte used for the treatment of leukaemic meningitis with concurrent systemic chemotherapy is a highly effective and feasible treatment in isolated and combined CNS relapse in ALL. 3) DepoCyte is generally well tolerated when concurrent dexamethasone is administered to alleviate symptoms of arachnoiditis and concomitant administration of agents that cross the BBB is avoided. Reference: Glantz M et al. Randomized trial of a slow release versus a standard formulation of cytarabine for the intrathecal treatment of lymphomatous meningitis. J Clin Oncol 1999; 17: 3110-17. Disclosures: No relevant conflicts of interest to declare.

Outcome of 136 Children with Advanced Lymphoblastic Lymphoma Receiving an BFM-Type Therapy with Intensified Maintenance: A Report from the Japanese Pediatric Leukemia/Lymphoma Study Group ALB-NHL03 Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3049-3049
Author(s):  
Shosuke Sunami ◽  
Masahiro Sekimizu ◽  
Tetsuya Takimoto ◽  
Tetsuya Mori ◽  
Tetsuo Mitsui ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Lymphoblastic Leukemia ◽  
Lymphoblastic Lymphoma ◽  
High Dose ◽  
Induction Phase ◽  
Pediatric Leukemia ◽  
Cns Disease ◽  
Stage 4 ◽  
Mediastinal Disease ◽  
Significant Difference

Abstract BACKGROUND: Lymphoblastic lymphoma (LBL) accounts for 30% of childhood non Hodgkin’s lymphoma in Japan. From European and North American groups, favorable results have been reported, using treatment strategies for acute lymphoblastic leukemia, over 80% of event free survival rate even in advanced LBL. However there were few data on Japanese or Asian patients with LBL. Here we report final outcome of first nation-wide prospective study over one hundred cases with advanced childhood LBL from Japan. PATIENTS & METHOD: Patients with stage 3 or 4 LBL received for 9 weeks induction phase, which consisted of 7 drugs and triple IT , followed by three courses of high dose MTX(5g/m2). After high dose MTX, re-induction, early maintenance, and late maintenance phase were administered. With an attempt to intensify maintenance therapy,early maintenance was consisted by two cycles of four courses of six drugs(MTX, PSL,VCR, L-ASP, 6MP, THP#) and late maintenance was five cycles of five drugs(MTX, PSL,VCR, 6MP,AraC). We omitted local radiotherapy including prophylactic cranial radiotherapy except patient with initial central nervous system (CNS) disease. The total duration of the treatment was 24 month‚“. RESULTS: From November 2004 to October 2010, 154 children with newly diagnosed advanced stage LBL were entered in this study. A total of 136 cases were eligible. Ages ranged from four month to 15 years, with a median of 9.07 years. Of the 136 patients, 36 were girls and 100 were boys. The distribution of clinical stage 3 and stage 4 was 82 and 54 patients respectively. 94 patients had primary mediastinal disease. 41 patients had BM disease, 31 patients had CNS disease and 8 patients had BM and CNS disease. 104 patients (76.5%) had precursor T LBL (T-LBL), 31 patients (22.8%) had precursor B LBL (B-LBL), onepatient (0.7%) had bi phenotype LBL. The follow-up time ranged from 2.8 to 94 months, with a median 58 months. For the 136 patients analyzed in this study, 5-year OS was 82.9% and 5-year EFS was 77.9%. There was no significant difference in outcome by gender (5-year EFS, male 78.2% vs. female 73.0%), or by immunophenotype (5-year EFS, B-LBL 80.7% vs. T-LBL 76.9%). Of note, the 5-year EFS for stage 3 T-LBL patients were worse than that of stage 4 T-LBL patients (70.6% vs. 88.9%, P=0.031). There were also significant difference in 5-year EFS for T-LBL patients who achieved CR and CRu at end of induction, 86.9%, and 69.7% (P=0.034), respectively.Most events were observed as mediastinum enlargement before initiation of intensified maintenance therapy. CONCLUSIONS: Our firstnationwide study provided about 80% cure rate with only one case of toxic death in childhood advanced LBL. However, our intensified maintenance therapy could not improve survival outcome. Our result also emphasize the significant difference between T-LBL stage 3 and stage 4 and might suggest the difference in ethnicity for the composition of biological subgroup in T-LBL. THP: Pirarubicin Disclosures No relevant conflicts of interest to declare.

scholarly journals Value of High-Dose Cytarabine During Interval Therapy of a Berlin-Frankfurt-Munster–Based Protocol in Increased-Risk Children With Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma: Results of the European Organization for Research and Treatment of Cancer 58881 Randomized Phase III Trial

2001 ◽  
Vol 19 (7) ◽  
pp. 1935-1942 ◽  
Author(s):  
F. Millot ◽  
S. Suciu ◽  
N. Philippe ◽  
Y. Benoit ◽  
F. Mazingue ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Lymphoblastic Lymphoma ◽  
Phase Iii ◽  
Stage Iii ◽  
High Dose ◽  
Treatment Schedule ◽  
European Organization ◽  
Cns Relapse ◽  
Increased Risk

PURPOSE: The European Organization for Research and Treatment of Cancer 58881 study was designed to test in a prospective multicentric randomized trial the value of high-dose (HD) intravenous (IV) cytarabine (Ara-C) added to HD IV methotrexate (MTX) to reduce the incidence of CNS and systemic relapses in children with increased-risk acute lymphoblastic leukemia (ALL) or stage III and IV lymphoblastic lymphoma treated with a Berlin-Frankfurt-Munster (BFM)–based regimen. PATIENTS AND METHODS: After completion of induction-consolidation phase, children with increased-risk (risk factor > 0.8 or T-lineage) ALL or stage III and IV lymphoblastic lymphoma were randomized to receive four courses of HD MTX (5 g/m2 over 24 hours every 2 weeks) and four intrathecal administrations of MTX (Arm A) or the same treatment schedule with additional HD IV Ara-C (1 g/m2 in bolus injection 12 and 24 hours after the start of each MTX infusion) (Arm B). RESULTS: Between January 1990 and January 1996, 653 patients with ALL (593 patients) or lymphoblastic lymphoma (60 patients) were randomized: 323 were assigned to Arm A (without Ara-C) and 330 to Arm B (with Ara-C). A total of 190 events (177 relapses and 13 deaths without relapse) were reported, and the median follow up was 6.5 years (range, 2 to 10 years). The incidence rates of CNS relapse were similar in both arms whether isolated (5.6% and 3.3%, respectively) or combined (5.3% and 4.6%, respectively). The estimated 6-year disease-free survival (DFS) rate was similar (log-rank P = .67) in the two treatment groups: 70.4% (SE = 2.6%) in Arm A and 71.0% (SE = 2.5%) in Arm B. The 6-year DFS rate was similar for ALL and LL patients: 70.2% (SE = 1.9%) versus 76.3% (SE = 5.6%). CONCLUSION: Prevention of CNS relapse was satisfactorily achieved with HD IV MTX and intrathecal injections of MTX in children with increased-risk ALL or stage III and IV lymphoblastic lymphoma treated with our BFM-based treatment protocol in which cranial irradiation was omitted. Disappointingly, with the dose schedule used in this protocol, HD Ara-C added to HD MTX, although well tolerated, failed to further decrease the incidence of CNS relapse or to improve the overall DFS.

High-dose cytosine arabinoside therapy for refractory leukemia

Blood ◽  
1983 ◽  
Vol 62 (2) ◽  
pp. 361-369 ◽  
Author(s):  
RH Herzig ◽  
SN Wolff ◽  
HM Lazarus ◽  
GL Phillips ◽  
C Karanes ◽  
...  
Keyword(s):  
Cytosine Arabinoside ◽  
Liver Toxicity ◽  
Lymphoblastic Leukemia ◽  
Skin Toxicity ◽  
Maximum Tolerated Dose ◽  
Myelogenous Leukemia ◽  
High Dose ◽  
Antileukemic Activity ◽  
Duration Of Treatment ◽  
Platelet Recovery

Abstract Fifty-seven patients with refractory acute leukemia were treated with high-dose cytosine arabinoside to establish the maximum tolerated dose and duration and to determine the antileukemic activity. The maximum tolerated regimen was found to be 3 g/sq m every 12 hr for 6 days. At this dose, nonhematologic toxicity was limited to conjunctivitis in approximately half of the patients, and liver toxicity (transient elevations in transaminase, alkaline phosphatase, or bilirubin) was frequently observed, but neither was dose-limiting. Extending the duration of treatment to 8 days resulted in excessive diarrhea and skin toxicity (painful erythema with bullae), while increasing the dose to 4.5 g/sq m q. 12 hr for 6 days resulted in severe cerebellar toxicity. Myelosuppression was severe, but was not related to the intensity of treatment; granulocyte recovery occurred a median of 28 days (range 22- 40 days) after initiating therapy, and platelet recovery occurred after a median of 25 days (range 16–41 days). Antileukemic activity was evaluable in the 46 patients who survived at least 3 wk. Complete remissions were obtained in 1 of 6 patients with chronic myelogenous leukemia (CML) in accelerated phase and 1 of 3 acute lymphoblastic leukemia (ALL) patients. A more detailed analysis of response was possible for the 37 evaluable patients with acute nonlymphoblastic leukemia: 70% of these patients responded, with 51% complete remissions. The median unmaintained response was 4 mo (range 2–26+ mo). The complete response rate was higher in patients who received at least 12 doses of high-dose cytosine arabinoside compared to shorter regimens [17/28 (61%) versus 2/9 (22%), p less than 0.05]. Resistance to cytosine arabinoside in conventional doses was documented in 11 patients, 5 of whom responded (2 complete remissions) to high-dose regimens. We conclude that high-dose cytosine arabinoside in the maximally tolerated regimen of 3 g/sq m every 12 hr for 6 days has substantial antileukemic activity in patients refractory to standard therapy. Durable unmaintained remissions can be achieved, even in patients who fail to respond to cytosine arabinoside in conventional doses.

scholarly journals Sustained long-term hematopoiesis after myeloablative therapy with peripheral blood progenitor cell support

Blood ◽  
1995 ◽  
Vol 85 (12) ◽  
pp. 3754-3761 ◽  
Author(s):  
R Haas ◽  
B Witt ◽  
R Mohle ◽  
H Goldschmidt ◽  
S Hohaus ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Progenitor Cell ◽  
Lymphoblastic Leukemia ◽  
Peripheral Blood Progenitor Cell ◽  
Myelogenous Leukemia ◽  
High Dose ◽  
Platelet Recovery ◽  
Cd34 Cells

A retrospective analysis of long-term hematopoiesis was performed in a group of 145 consecutive patients who had received high-dose therapy with peripheral blood progenitor cell (PBPC) support between May 1985 and December 1993. Twenty-two patients had acute myelogenous leukemia, nine had acute lymphoblastic leukemia, 43 had Hodgkin's disease, 57 had non- Hodgkin's lymphoma, and 14 patients had multiple myeloma. Eighty-four patients were male and 61 female, with a median age of 37 years (range, 16 to 58 years). In 46 patients, PBPC were collected after cytotoxic chemotherapy alone, while 99 patients received cytokines either during steady-state hematopoiesis or post-chemotherapy. Sixty patients were treated with dose-escalated polychemotherapy, and 85 patients had a conditioning therapy including hyperfractionated total body irradiation at a total dose of 14.4 Gy. The duration of severe pancytopenia posttransplantation was inversely related to the number of reinfused granulocyte-macrophage colony-forming units (CFU-GM) and CD34+ cells. Threshold quantities of 2.5 x 10(6) CD34+ cells per kilogram or 12.0 x 10(4) CFU-GM per kilogram became evident and were associated with rapid neutrophil and platelet recovery within less than 18 and 14 days, respectively. These numbers were also predictive for long-term reconstitution, indicating that normal blood counts are likely to be achieved within less than 10 months after transplantation. Conversely, 12 patients were autografted with a median of 1.75 x 10(4) CFU-GM per kilogram resulting in delayed recovery to platelet counts of greater than 150 x 10(9)/L between 1 and 6 years. Our study includes bone marrow examinations in 50 patients performed at a median follow-up time of 10 months (range, 1 to 85 months) posttransplantation. A comparison with normal volunteers showed a 3.2-fold smaller proportion of bone marrow CD34+ cells, which was paralleled by an even more pronounced reduction in the plating efficiency of CFU-GM and burst-forming unit-erythroid. No secondary graft failure was observed, even in patients autografted with relatively low numbers of progenitor cells. This suggests that either the pretransplant regimens were not myeloablative, allowing autochthonous recovery, or that a small number of cells capable of perpetual self-renewal were included in the autograft products.

scholarly journals Fractionated total body irradiation and high-dose etoposide as a preparatory regimen for bone marrow transplantation for 99 patients with acute leukemia in first complete remission

Blood ◽  
1993 ◽  
Vol 82 (9) ◽  
pp. 2920-2928 ◽  
Author(s):  
DS Snyder ◽  
NJ Chao ◽  
MD Amylon ◽  
J Taguchi ◽  
GD Long ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Complete Remission ◽  
Acute Leukemia ◽  
Lymphoblastic Leukemia ◽  
Myelogenous Leukemia ◽  
High Dose ◽  
Graft Versus Host ◽  
Acute Myelogenous ◽  
Total Body ◽  
First Complete Remission

Abstract Ninety-nine consecutive patients with acute leukemia in first complete remission under age 50 (median age 27 years; age range 1 to 47 years) with a histocompatible sibling donor were treated with fractionated total body irradiation (1,320 cGy) and high-dose etoposide (60 mg/kg) followed by allogeneic bone marrow transplantation. Sixty-one patients were diagnosed with acute myelogenous leukemia (AML), 34 patients with acute lymphoblastic leukemia (ALL), 3 patients with biphenotypic acute leukemia, and 1 patient with acute undifferentiated leukemia. Thirty of the 34 patients with ALL had at least one of the following high-risk factors: age greater than 30, white blood cell count at presentation > 25,000/microL, extramedullary disease, certain chromosomal translocations, or the need for greater than 4 weeks of induction chemotherapy to achieve first complete remission. Cumulative probabilities of disease-free survival and relapse at 3 years were 61% and 12%, respectively, for the 61 patients with AML and 64% and 12%, respectively, for the 34 patients with ALL. By stepwise Cox regression analysis, significant prognostic variables for patients with acute myelogenous leukemia were the presence of acute graft-versus-host disease and increasing age, whereas for patients with acute lymphoblastic leukemia, significant variables were age and the development of cytomegalovirus-associated interstitial pneumonia. Complications related to graft-versus-host disease and relapse of leukemia were the major causes of death.

Central Nervous System Involvement in Adult Acute Lymphoblastic Leukemia (ALL) at Diagnosis and/or at First Relapse: Results from the GET-LALA Group.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4326-4326
Author(s):  
Oumedaly Reman ◽  
Arnaud Pigneux ◽  
Francoise Huguet ◽  
Norbert Vey ◽  
Andre Delannoy ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Lymphoblastic Leukemia ◽  
Central Nervous System Involvement ◽  
Unrelated Donor ◽  
Cns Involvement ◽  
Cns Disease ◽  
Cns Relapse ◽  
First Relapse ◽  
B Lineage

Abstract Outcome of adult ALL with central nervous system (CNS) involvement is not clearly defined. We studied 104 patients presenting with CNS involvement at diagnosis among 1493 patients (7%) included into the LALA-87 or LALA-94 trials, and 109 patients (9% of first remitters) presenting CNS disease at the time of first relapse among the 709 relapsing patients (15%) included initially in these trials. Treatment of patients presenting CNS involvement at diagnosis consisted in initial chemotherapy completed by 18 double or triple intrathecal injections associated with 15 to 20 Gy cranial irradiation, followed when possible by intensification by allogeneic or autologous stem cell transplantation (SCT). At diagnosis, 43 patients (41%) presenting with CNS involvement had T-lineage ALL, 53 (51%) had B-lineage ALL (of whom 9 were diagnosed as Philadelphia (Ph) chromosome positive ALL), 8 had undifferentiated ALL or unknown immunophenotype. Eighty-seven of 104 (84%) patients with CNS involvement at diagnosis achieved complete remission (CR). Fifty-three patients underwent SCT (25 allogeneic SCT from matched related or unrelated donor, 28 autologous SCT). Overall survival at 7 years was 34% in those with CNS involvement at diagnosis versus 29% (p = NS) for those without. DFS at 7 years was 35% versus 28% (p = NS). There were no significant differences between patients with CNS involvement and those without CNS involvement regarding T lineage ALL, B lineage ALL (including or not Ph ALL). There were also no significant differences regarding patients who underwent transplantation as consolidation intensification, while in patients receiving only chemotherapy patients without initial CNS involvement had a better outcome (p = 0.01). Among the 709 patients with primary relapse, 66 patients (61%) presented a CNS relapse combined with bone marrow relapse, whereas 17 relapses (15%) and 26 relapses (24%) were CNS relapses combined with another extramedullary relapse or isolated CNS relapses respectively. Median time to relapse was 6.7 months (range, 1–62) in patients with CNS relapse versus 11.2 months (1.7–111) in relapsing patients without CNS involvement. Eleven patients (10%) with CNS relapse had CNS involvement at diagnosis, while 98 patients were diagnosed with CNS disease only at the time of first relapse. Overall, 38 out of 109 patients with CNS relapse (35%) achieved CR. The median OS was 6.3 months. Outcome was similar in terms of CR proportion and OS in relapsing patients without CNS involvement. The 2-year OS rates did not show any difference among patients with CNS relapse who had CNS involvement at diagnosis and those with CNS disease only diagnosed at the time of first relapse.Overall, CNS leukemia in adult ALL is uncommon at diagnosis. Patients have a similar outcome than those who did not present with CNS involvement. However, patients benefit from intensification therapy by autologous or allogeneic SCT. CNS leukemia at first relapse are also uncommon but probably underestimated. Outcome is particularly poor as this of all adult ALL in first relapse.

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