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M.B. Geyer et al.
DFS was defined as time from post-induction I or II disease assessment until morphologic relapse or death; patients without any of these events were censored on date of last follow-up. In order to compare OS between patients undergoing versus not undergoing allogeneic hematopoietic cell transplantation (alloHCT) in CR1, OS was measured from date of first confirmed CR. Statistical analyses were performed in R v3.5.0. A 2-sided P- value <0.05 was considered significant.
Results
Patients characteristics
Demographic and clinical characteristics of treated patients are summarized in Table 2. Of the 39 patients, 30 (77%) were men. Median age at the start of treatment was 38.7 years (range, 20.2-60.4 years); 18 (46%) patients were 40-60 years old. Lineage was B cell in 27 (69%) patients (ALL, n=24; LBL, n=3) and T cell in 12 patients (ALL, n=7; LBL, n=5). Three patients had central nervous system
(CNS)-2/3 cerebrospinal fluid (n=2) or parenchymal brain involvement (n=1) and 16 had extramedullary disease at diagnosis. Five of 12 patients with T-cell ALL/LBL demon- strated early T-precursor phenotype as previously defined.29 Cytogenetic findings associated with unfavor- able risk (per classification used in the CALGB 19802 study; Online Supplementary Table S3) were observed in five patients (11q23 rearrangement, n=2; trisomy 8, n=2; monosomy 7, n=1). Among 11 patients with B-ALL/LBL who underwent evaluation for fusions/re-arrangements characteristic of Philadelphia chromosome-like (“Ph-like”) ALL (see the Online Supplementary Methods), only one case was identified (FIP1L1-PDGFRA fusion).
Clinical responses
Thirty-eight of 39 (97%) patients achieved CR or CR with incomplete hematologic recovery (CRi) by the con- clusion of induction II. Following induction I, 36 of 38 (95%) of evaluable patients were in CR/CRi. Of the two patients who were not in CR/CRi, both had T-cell ALL;
Table 1. Treatment regimen. Regimen Block
Induction Phase I
Induction Phase II
Intensification I
Re-induction I
Intensification II
Re-induction II
Maintenance
(Monthly for 36 months total)
Agent
Daunorubicin Vincristine Pegaspargase Prednisone Methotrexate Hydrocortisone
Cyclophosphamide Cytarabine Mercaptopurine Vincristine Pegaspargase Prednisone Methotrexate Hydrocortisone2
Methotrexate
Leucovorin* Pegaspargase Prednisone
Daunorubicin Vincristine Pegaspargase Dexamethasone Methotrexate Hydrocortisone Cyclophosphamide Cytarabine Thioguanine
Same as intensification I Same as re-induction I Prednisone
Vincristine Methotrexate
Mercaptopurine Methotrexate Hydrocortisone
Dose
60 mg/m2
1.4 mg/m2 (cap 2 mg) 2,000 U/m2
60 mg/m2
12 mg
25 mg
1 g/m
75 mg/m2
60 mg/m2
1.4 mg/m2 (cap 2 mg) 2,000 U/m2
20 mg
12 mg
25 mg
3.5 g/m2 (B-cell) 5 g/m2 (T-cell) 25 mg 2,000 U/m2
20 mg
25 mg/m2
1.4 mg/m2 (cap 2 mg) 2,000 U/m2
10 mg/m2
12 mg
25 mg
1 g/m2
75 mg/m2
60 mg/m2
60 mg/m2
1.4 mg/m2 (cap 2 mg) 10 mg/m2
60 mg/m2 12 mg 25 mg
Route
IV push IVPB/IV push IVPB over 1-2h PO
IT
IT
IVPB IVPB
PO IVPB/IV push IVPB over 1-2h PO
IT
IT
IVPB over 3h IVPB over 3h IVPB q6h IVPB over 1-2h PO
IV push IVPB/IV push IVPB over 1-2h PO
IT
IT
IVPB IVPB
PO
PO
IV PO
PO IT IT
Days
1,2,3 1,8,15,22 15 1-28 8,15 8.15
1,29 1-4,8-11,29-32,36-39 1-14,29-42 1,15,29,43
15
15-22 1,15,29,43 1,15,29,43
1,15
1,15
24h from start of MTX 16 or 17
15-22
1,8,15 1,8,15,29,43 15 15-22,29-36 1,8,29 1,8,29 29 29-32,36-39 29-42
1-5 (q mon, mon. 1-12; q2 mon, mon. 13-24)
1 (q mon, mon. 1-12; q2 mon, mon. 13-36) 1,8,15,22 (held on days of IT MTX)
1-28, daily
1 (q3 mon, mon. 1-12) 1 (q3 mon, mon. 1-12)
*Leucovorin rescue following the day 15 dose of high-dose methotrexate was started prior to administration of pegaspargase. IVPB: intravenous piggy back; PO: by mouth; IT: intrathecal; MTX: methotrexate, mon: month; cap: capped; q2: calender quarter 2 (April, May, and June); q3: calender quarter 3 (July, August, and Septembe).
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haematologica | 2021; 106(8)