Relation between the duration of remission and hyperglycemia during induction chemotherapy for acute lymphocytic leukemia with a hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone/methotrexate-cytarabine regimen.
BACKGROUND
Hyperglycemia, which is not uncommon during the treatment of acute lymphocytic leukemia (ALL), has been shown to be an independent predictor of adverse outcomes among hospitalized patients with undiagnosed diabetes; it also may have the potential to affect leukemic cell proliferation through altered metabolism. The purpose of the current study was to determine the prevalence of hyperglycemia during induction chemotherapy for ALL using a regimen comprised of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD) and to determine its effect on survival, duration of disease remission, and treatment-related complications.


METHODS
Two hundred seventy-eight adult patients with previously untreated ALL who achieved a complete remission with the hyper-CVAD regimen were evaluated. Hyperglycemia was defined as > or = 2 glucose determinations of > or = 200 mg/dL during the first 30 days of induction chemotherapy. Induction chemotherapy was comprised of fractionated cyclophosphamide at a dose of 300 mg/m2 twice daily on Days 1-3, doxorubicin at a dose of 50 mg/m2 on Day 4, vincristine at a dose of 2 mg on Days 4 and 11, and dexamethasone at a dose of 40 mg on Days 1-4 and Days 11-14 (hyper-CVAD). Hyper-CVAD, given in odd-number courses (Courses 1, 3, 5, and 7), was alternated with methotrexate and cytarabine (MTX/Ara-C), given in even-number courses (Courses 2, 4, 6, and 8). MTX/Ara-C was comprised of MTX at a dose of 200 mg/m2 over 2 hours followed by 800 mg/m2 over 22 hours on Day 1, Ara-C at a dose of 3 g/m2 every 12 hours for 4 doses over 2 days (Days 2 and 3), and intravenous methylprednisolone given at a dose of 50 mg twice daily on Days 1-3. The complete remission duration (CRD), survival, and treatment-related complications were determined for patients with and without hyperglycemia; differences between the two groups were assessed using standard statistical methods.


RESULTS
Hyperglycemia was found to occur in 103 patients (37%). Patients with hyperglycemia had a shorter median CRD (24 months vs. 52 months; P = 0.001) and a shorter median survival (29 months vs. 88 months; P < 0.001); they also were more likely to develop sepsis (16.5% vs. 8.0%; P = 0.03) or any complicated infection (sepsis, pneumonia, or fungal) (38.8% vs. 25.1%; P = 0.016) compared with patients without hyperglycemia.


CONCLUSIONS
Patients with hyperglycemia during induction chemotherapy for ALL with the hyper-CVAD regimen were found to have a shorter CRD, experience a significant increase in overall mortality, and be at an increased risk for developing complicated infections.
Weiser
Mary Ann
MA
Department of General Internal Medicine, Ambulatory Treatment and Emergency Care, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. mweiser@mdanderson.org
Cabanillas
Maria E
ME
Konopleva
Marina
M
Thomas
Deborah A
DA
Pierce
Sherry A
SA
Escalante
Carmen P
CP
Kantarjian
Hagop M
HM
O'Brien
Susan M
SM
D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000009:adverse effects* / Q000627:therapeutic use*; D003561:Cytarabine / Q000009:adverse effects / Q000627:therapeutic use; D003907:Dexamethasone / Q000009:adverse effects* / Q000627:therapeutic use*; D004317:Doxorubicin / Q000009:adverse effects* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000209:etiology*; D007239:Infections / Q000209:etiology; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality; D012074:Remission Induction; D013997:Time Factors; D014750:Vincristine / Q000009:adverse effects* / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D003561:Cytarabine; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; D008727:Methotrexate