scholarly journals Improved outcome in adult B-cell acute lymphoblastic leukemia

Blood ◽  
1996 ◽  
Vol 87 (2) ◽  
pp. 495-508 ◽  
Author(s):  
D Hoelzer ◽  
WD Ludwig ◽  
E Thiel ◽  
W Gassmann ◽  
H Loffler ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Intensive Therapy ◽  
Intrathecal Methotrexate ◽  
Intrathecal Therapy ◽  
High Dose ◽  
Male Predominance ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Wbc Count

A total of 68 adult patients with B-cell acute lymphoblastic leukemia (B-ALL) were treated in three consecutive adult multicenter ALL studies. The diagnosis of B-ALL was confirmed by L3 morphology and/or by surface immunoglobulin (Slg) expression with > 25% blast cell infiltration in the bone marrow (BM). They were characterized by male predominance (78%) and a median age of 34 years (15 to 65 y) with only 9% adolescents (15 to 20 y), but 28% elderly patients (50 to 65 y). The patients received either a conventional (N = 9) ALL treatment regimen (ALL study 01/81) or protocols adapted from childhood B-ALL with six short, intensive 5-day cycles, alternately A and B. In study B-NHL83 (N = 24) cycle A consisted of fractionated doses of cyclophosphamide 200 mg/m2 for 5 days, intermediate-dose methotrexate (IdM) 500 mg/m2 (24 hours), in addition to cytarabine (AraC), teniposide (VM26) and prednisone. Cycle B was similar except that AraC and VM26 were replaced by doxorubicin. Major changes in study B-NHL86 (N = 35) were replacement of cyclophosphamide by ifosphamide 800 mg/m2 for 5 days, an increase of IdM to high-dose, 1,500 mg/m2 (HdM) and the addition of vincristine. A cytoreductive pretreatment with cyclophosphamide 200 mg/m2, and prednisone 60 mg/m2, each for 5 days was recommended in study B-NHL83 for patients with high white blood cell (WBC) count (e 2,500/m2) or large tumor burden and was obligatory for all patients in study B-NHL86. Central nervous system (CNS) prophylaxis/treatment consisted of intrathecal methotrexate (MTX) therapy, later extended to the triple combination of MTX, AraC, and dexamethasone, and a CNS irradiation (24 Gy) after the second cycle. Compared with the ALL 01/81 study where all the patients died, results obtained with the pediatric protocols B-NHL83 and B-NHL86 were greatly improved. The complete remission (CR) rates increased from 44% to 63% and 74%, the probability of leukemia free survival (LFS) from 0% to 50% and 71% (P = .04), and the overall survival rates from 0% to 49% and 51% (P = .001). Toxicity, mostly hematotoxicity and mucositis, was severe but manageable. In both studies B-NHL83 and B-NHL86, almost all relapses occurred within 1 year. The time to relapse was different for BM, 92 days, and for isolated CNS and combined BM and CNS relapses, 190 days (P = .08). The overall CNS relapses changed from 50% to 57% and 17%, most probably attributable to the high-dose MTX and the triple intrathecal therapy. LFS in studies B-NHL83 and B-NHL86 was significantly influenced by the initial WBC count < or > 50,000/microL, LFS 71% versus 29% (P = .003) and hemoglobin value > or < 8 g/dL, LFS 67% versus 27% (P = .02). Initial CNS involvement had no adverse impact on the outcome. Elderly B- ALL patients (> 50 years) also benefited from this treatment with a CR rate of 56% and a LFS of 56%. It is concluded that this short intensive therapy with six cycles is effective in adult B-ALL. HdM and fractionated higher doses of cyclophosphamide or ifosphamide seem the two major components of treatment.

Role of cranial radiotherapy for childhood T-cell acute lymphoblastic leukemia with high WBC count and good response to prednisone. Associazione Italiana Ematologia Oncologia Pediatrica and the Berlin-Frankfurt-Münster groups.

1997 ◽  
Vol 15 (8) ◽  
pp. 2786-2791 ◽  
Author(s):  
V Conter ◽  
M Schrappe ◽  
M Aricó ◽  
A Reiter ◽  
C Rizzari ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Lymphoblastic Leukemia ◽  
Group Versus ◽  
Rank Test ◽  
Intrathecal Methotrexate ◽  
Intrathecal Therapy ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Wbc Count ◽  
The Impact

PURPOSE The ALL-BFM 90 and AIEOP-ALL 91 studies share the same treatment backbone and have 5-year event-free survival (EFS) rates close to 75%. This study evaluated the impact of differing presymptomatic CNS therapies in T-cell acute lymphoblastic leukemia (T-ALL) patients with a good response to prednisone (PGR) according to WBC count and Berlin-Frankfurt-Münster (BFM) risk factor (RF). PATIENTS A total of 192 patients (141 boys; median age, 7.5 years) with T-ALL, PGR, RF less than 1.7, and no CNS leukemia diagnosed between 1990 and 1995 were enrolled onto the ALL-BFM 90 (n = 123) or AIEOP-ALL 91 (n = 69) study. Presymptomatic CNS therapy consisted of cranial radiation (CRT) and intrathecal methotrexate (I.T. MTX) (11 doses) in the BFM study and of extended triple intrathecal therapy (T.I.T.) (17 doses) in the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) study. Patients were divided into a low-WBC group (WBC count < 100,000/microL) and a high-WBC group (WBC count > 100,000/microL). EFS was compared using the log-rank test. RESULTS For patients treated with CRT and I.T. MTX (BFM group), the 3-year EFS rate was 89.8% (SE = 3.5) for 99 patients in the low-WBC group versus 81.9% (SE = 8.2) in the high-WBC group (difference not significant). Conversely, for patients treated with T.I.T. alone (AIEOP group), the EFS rate was 80.6% (SE = 5.6) in 55 patients with a low WBC count versus 17.9% (SE = 11.0) in 14 patients with a high WBC count (P < .001). CONCLUSION These data suggest that CRT may not be necessary in PGR T-ALL patients with a WBC count less than 100,000/microL; on the contrary, in patients with a high count, extended T.I.T. may be inferior to CRT and I.T. MTX.

scholarly journals Favorable outcome of B-cell acute lymphoblastic leukemia in childhood: a report of three consecutive studies of the BFM group

Blood ◽  
1992 ◽  
Vol 80 (10) ◽  
pp. 2471-2478 ◽  
Author(s):  
A Reiter ◽  
M Schrappe ◽  
WD Ludwig ◽  
F Lampert ◽  
J Harbott ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Residual Disease ◽  
Short Pulse ◽  
Lymphoblastic Leukemia ◽  
Pulse Therapy ◽  
Intrathecal Therapy ◽  
High Dose ◽  
Increased Risk ◽  
Cell Acute Lymphoblastic Leukemia

Abstract In 1981 the BFM group introduced a new treatment strategy for B-cell acute lymphoblastic leukemia (B-ALL). A cytoreductive prephase (prednisone/cyclophosphamide) was followed by eight 5-day courses of chemotherapy. Fractionated cyclophosphamide, methotrexate (MTX) 0.5 g/m2 (24-hour infusion), and MTX intrathecally were administered at each course and cytosine arabinoside (ARA-C)/teniposide (VM-26) was given alternately with doxorubicin. In study ALL-BFM-83, central nervous system (CNS) chemotherapy was intensified by adding dexamethasone, while MTX/ARA-C was administered intraventricularly. Therapy duration was reduced to six courses. In study ALL-BFM-86, MTX 0.5 g/m2 was replaced by high-dose (HD) MTX, 5 g/m2 (24-hour infusion), and MTX/ARA-C/prednisolone intrathecal therapy was introduced. Doses of ARA-C and VM-26 were increased and fractionated, cyclophosphamide was partially replaced by ifosfamide, and vincristine was added. CNS irradiation was 24 Gy for prevention and 30 Gy for overt disease in studies ALL-BFM-81 and -83, but was omitted in ALL-BFM-86. In all, 87 patients were enrolled, 22 (8 CNS-positive) in study All-BFM-81, 24 (7 CNS-positive) in study ALL-BFM-83, and 41 (0 CNS-positive) in study ALL- BFM-86. The estimated 5-year duration of event-free survival (EFS) was 43% in study ALL-BFM 81, 50% in study ALL-BFM-83, and 78% in study ALL- BFM-86 (minimal follow-up, 25 months). Nineteen of 24 relapses occurred while on therapy or shortly thereafter. In study ALL-BFM 81, the CNS was the most frequent site of failure. In ALL-BFM-83, there were no isolated CNS relapses, but more bone marrow (BM) relapses occurred. In ALL-BFM-86, localized manifestations were the predominant site of failure, no isolated BM relapses occurred, and only one CNS relapse was diagnosed. No single parameter exerted a consistent influence on outcome with one exception. The presence of residual disease after the first two courses was correlated with an increased risk of therapy failure. We conclude that an intensive, short-pulse therapy delivered within a 4-month period is highly effective in the treatment of B-ALL. In addition to fractionated cyclophosphamide/ifosfamide, a 24-hour infusion of HD MTX 5 g/m2 in conjunction with an i.th. therapy is an important component for prevention of both systemic and CNS relapses. CNS irradiation is not needed for CNS-negative patients.

scholarly journals Favorable outcome of B-cell acute lymphoblastic leukemia in childhood: a report of three consecutive studies of the BFM group

Blood ◽  
1992 ◽  
Vol 80 (10) ◽  
pp. 2471-2478 ◽  
Author(s):  
A Reiter ◽  
M Schrappe ◽  
WD Ludwig ◽  
F Lampert ◽  
J Harbott ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Residual Disease ◽  
Short Pulse ◽  
Lymphoblastic Leukemia ◽  
Pulse Therapy ◽  
Intrathecal Therapy ◽  
High Dose ◽  
Increased Risk ◽  
Cell Acute Lymphoblastic Leukemia

In 1981 the BFM group introduced a new treatment strategy for B-cell acute lymphoblastic leukemia (B-ALL). A cytoreductive prephase (prednisone/cyclophosphamide) was followed by eight 5-day courses of chemotherapy. Fractionated cyclophosphamide, methotrexate (MTX) 0.5 g/m2 (24-hour infusion), and MTX intrathecally were administered at each course and cytosine arabinoside (ARA-C)/teniposide (VM-26) was given alternately with doxorubicin. In study ALL-BFM-83, central nervous system (CNS) chemotherapy was intensified by adding dexamethasone, while MTX/ARA-C was administered intraventricularly. Therapy duration was reduced to six courses. In study ALL-BFM-86, MTX 0.5 g/m2 was replaced by high-dose (HD) MTX, 5 g/m2 (24-hour infusion), and MTX/ARA-C/prednisolone intrathecal therapy was introduced. Doses of ARA-C and VM-26 were increased and fractionated, cyclophosphamide was partially replaced by ifosfamide, and vincristine was added. CNS irradiation was 24 Gy for prevention and 30 Gy for overt disease in studies ALL-BFM-81 and -83, but was omitted in ALL-BFM-86. In all, 87 patients were enrolled, 22 (8 CNS-positive) in study All-BFM-81, 24 (7 CNS-positive) in study ALL-BFM-83, and 41 (0 CNS-positive) in study ALL- BFM-86. The estimated 5-year duration of event-free survival (EFS) was 43% in study ALL-BFM 81, 50% in study ALL-BFM-83, and 78% in study ALL- BFM-86 (minimal follow-up, 25 months). Nineteen of 24 relapses occurred while on therapy or shortly thereafter. In study ALL-BFM 81, the CNS was the most frequent site of failure. In ALL-BFM-83, there were no isolated CNS relapses, but more bone marrow (BM) relapses occurred. In ALL-BFM-86, localized manifestations were the predominant site of failure, no isolated BM relapses occurred, and only one CNS relapse was diagnosed. No single parameter exerted a consistent influence on outcome with one exception. The presence of residual disease after the first two courses was correlated with an increased risk of therapy failure. We conclude that an intensive, short-pulse therapy delivered within a 4-month period is highly effective in the treatment of B-ALL. In addition to fractionated cyclophosphamide/ifosfamide, a 24-hour infusion of HD MTX 5 g/m2 in conjunction with an i.th. therapy is an important component for prevention of both systemic and CNS relapses. CNS irradiation is not needed for CNS-negative patients.

B Cell Aplasia In a Patient with Relapsed B Cell Acute Lymphoblastic Leukemia Following Re-Induction and Consolidation with Autologous T Cells Genetically Targeted to the CD19 Antigen

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3268-3268
Author(s):  
Marco L Davila ◽  
Clare Taylor ◽  
Xiuyan Wang ◽  
Jolanta Stefanski ◽  
Malgorzata Olszewska ◽  
...  
Keyword(s):  
Clinical Trial ◽  
T Cells ◽  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
B Cell ◽  
Induction Chemotherapy ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
Cell Acute Lymphoblastic Leukemia

Abstract Abstract 3268 Despite high initial remission rates following induction chemotherapy, most adults with B cell acute lymphoblastic leukemia (B-ALL) ultimately relapse and the overall prognosis is poor. In light of the overall poor outcomes seen with currently available chemotherapy regimens as well as allogeneic stem cell transplantation, novel and effective treatment approaches are needed for these patients. To this end, we have developed a program utilizing a patient's own T cells genetically modified ex vivo to express a chimeric antigen receptor (CAR), termed 19–28z, specific to the CD19 antigen expressed on normal B cells as well as most B-ALL tumors. In preclinical studies, human T cells modified to express the 19–28z CAR effectively eradicated systemic human B-ALL NALM-6 tumors in SCID-Beige mice. Based on these findings we have recently opened a phase I clinical trial (IRB #09-114) wherein patients with relapsed B-ALL are initially treated with re-induction chemotherapy followed by consolidation with high dose cyclophosphamide (3gm/m2) and a subsequent infusion of autologous T cells genetically modified to express the 19–28z CAR. Herein, we report the initial findings of the first patient treated on this clinical trial. This patient, a 67-year-old male, with B-ALL (normal cytogenetics), achieved a complete remission following induction chemotherapy with mitoxantrone and high-dose cytarabine. The patient remained in remission following treatment with vincristine (consolidation B) and cyclophosphamide (consolidation C). However, he was noted to have relapsed disease following consolidation cycle D with cytarabine and etoposide. At the time of relapse the patient was leukapheresed to obtain autologous T cells, and subsequently achieved a second remission following re-induction with a modified PEG-asparaginase, vincristine, and prednisone regimen. Upon recovery, the patient, as stipulated by the clinical trial, received lymphodepleting consolidation with high dose cyclophosphamide followed, 2 and 3 days later, by a split dose infusion of 3 × 106/kg autologous 19–28z+ T cells, the lowest planned T cell dose on this trial. Over the next 2 weeks, FACS and Q-PCR detected gene-modified T cells in the peripheral blood. Significantly, over the next 5 weeks, despite recovery of neutrophils and T cells, the patient exhibited a persistent B cell aplasia consistent with CD19-targeted cytotoxic activity of the infused autologous 19–28z+ T cells. The patient subsequently received an allogeneic stem cell transplant from a HLA-identical sibling effectively abrogating further analysis of modified T cell function. Despite this limitation, we conclude that following lymphodepleting chemotherapy, modified CD19-targeted T cells exhibit effective anti-CD19 cytotoxic activity, as demonstrated by the persistent B cell aplasia, in the clinical setting. These findings support the promise of this novel adoptive T cell therapy in patients with relapsed B-ALL. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Genetic Profile and Clinical Implications of PDGFRB Fusion in Adult B-Cell Acute Lymphoblastic Leukemia: A Retrospective Analysis

2021 ◽  
Author(s):  
Guofa Xu ◽  
Xie-bing Bao ◽  
Li-min Liu ◽  
Man Wang ◽  
Zhi-bo Zhang ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Kinase Inhibitor ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Intensive Therapy ◽  
Genetic Profile ◽  
Hematopoietic Stem ◽  
Car T ◽  
Cell Acute Lymphoblastic Leukemia

Abstract Background:To investigate the pathogenesis, genetic changes, treatment and prognosis of adult B-cell acute lymphoblastic leukemia (B-ALL) with platelet-derived growth factor receptor B (PDGFRB) fusion. Method：Clinical characteristics, treatment process and prognosis of 7 adult B-ALL patients with PDGFRB fusion were presented respectively, and the PDGFRB fusion was confirmed by fluorescence in situ hybridization, RNA sequencing and Polymerase Chain Reaction. Results: 7 adult B-ALL patients with PDGFRB fusion were presented respectively. There were 5 males and 2 females, with a median age of 21 (range, 17-39) years and a median white blood cell count of 7.85 (range, 2.30-111.25) ×10^9/L. The fusion partners were EBF1, SMIM3 and TERF2. Three of 7 cases received tyrosine kinase inhibitor (TKI) targeted therapy, and 4 of 7 cases received chimeric antigen receptor T -cell (CAR-T) therapy. A total of 6 (85.71%) cases underwent haploid hematopoietic stem cell transplantation (Haplo-HSCT). Overall response rate was 71.43% (4/7), and the common adverse reactions during induction were febrile neutropenia and nausea. Seventy-five percent (3/4) and 100% (6/6) of patients were minimal residual disease negative after CAR-T and Haplo-HSCT. To the last follow-up, 2 of 7 cases relapsed in 2 and 7 months after remission, respectively, and the estimated 36 months of Event-free survival and Overall survival was 75.0% and 66.7%.Conclusions: intensive therapy combined with CAR-T or TKI is needed to achieve deep remission, and sequential Haplo-HSCT may improve the prognosis of adult B-ALL with PDGFRB fusion.

HiC-COM: a 2-month intensive chemotherapy regimen for children with stage III and IV Burkitt's lymphoma and B-cell acute lymphoblastic leukemia.

1991 ◽  
Vol 9 (1) ◽  
pp. 133-138 ◽  
Author(s):  
M R Schwenn ◽  
S R Blattner ◽  
E Lynch ◽  
H J Weinstein
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Transverse Myelitis ◽  
Stage Iv ◽  
Burkitt’S Lymphoma ◽  
Burkitt's Lymphoma ◽  
Stage Iii ◽  
High Dose ◽  
Cell Acute Lymphoblastic Leukemia

We designed a protocol that included 2 months of intensive Cytoxan (cyclophosphamide; Bristol-Myers Co, Evansville, IN), high-dose methotrexate (MTX), high-dose cytarabine (ara-C), and vincristine (HiC-COM) to improve event-free survival (EFS) for patients with advanced-stage Burkitt's lymphoma and B-cell acute lymphoblastic leukemia (ALL). We also wished to test the feasibility of rapidly cycling Cytoxan and high-dose ara-C based on signs of early marrow recovery. Twenty patients including 12 with stage III Burkitt's lymphoma and eight with stage IV Burkitt's lymphoma or B-cell ALL were entered onto this pilot study. The rate of complete remission was 95%. Four patients have relapsed. The 2-year actuarial EFS was 75% (median follow-up, 37 months). Two of the initial five patients developed transverse myelitis, which we believe may have been secondary to the concomitant administration of intrathecal (IT) and high-dose systemic ara-C. We conclude that this short but intensive regimen is highly effective for patients with advanced Burkitt's lymphoma and B-cell ALL. EFS has improved over previous less intensive regimens, and is comparable to regimens of longer duration.

scholarly journals Infantile T-cell Acute Lymphoblastic Leukemia: a Case Report

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Natasha Baig ◽  
Sadia Muhammad ◽  
Sumaira Shaikh
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Treatment Guidelines ◽  
Lymphoblastic Leukemia ◽  
Young Patients ◽  
Cell Lineage ◽  
High Dose ◽  
Treatment Protocols ◽  
Male Predominance ◽  
Cell Acute Lymphoblastic Leukemia

Introduction: Acute lymphoblastic leukemia (ALL) is the most common malignancy in children, with a male predominance. Pediatric acute lymphoblastic leukemia is usually of B-cell lineage; T-cell leukemia is uncommon and extremely rare under one year of age. Mixed-lineage leukemia gene rearrangement is the best-known hallmark of infantile leukemia and is a poor prognostic indicator. While multi-agent high dose chemotherapy remains the first line of treatment for pediatric T-ALL, there are numerous side effects of these regimens, and most patients undergo relapse. Due to the rarity of the disease, treatment protocols for infantile T-ALL have not been established to date. Clinical description: We present a case of a 7-month-old Pakistani male that presented with fever and cough and was subsequently diagnosed with T cell acute lymphoblastic leukemia. T-ALL was diagnosed on flow cytometry. Due to poor prognosis, the patient was assigned palliative care. Practical implications: Management of infantile leukemia has yet to be studied in-depth. With a lack of clear treatment guidelines, the approach towards these patients remains challenging. Further research and clinical trials in this area of study are paramount to improving clinical outcomes for these young patients.

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