Table 2.
Summary of Hematological Changes Following LD-RT, HD-RT, Chemotherapy, and Chemoradiation.
| Cancer type | Dose/fractionation regimen | Hematological toxicities | Reference | ||
|---|---|---|---|---|---|
| Leukocytes | Thrombocytes | Erythrocytes/hemoglobin | |||
| LD-RT | |||||
| CLL | TBI of 3–10 cGy/fraction, 3–5 fractions/week, 100–400 cGy total | Thrombocytopenia in 15% | Anemia in 5% | Johnson 28 | |
| Lympho-sarcoma | TBI of 15–210 cGy in 2 fractions/week for 5 weeks | Mildly depressed | Occurred to some degree in all patients, treatment interruption in 1/3 | Mildly depressed | Chaffey et al 29 |
| NHL | Regimen A: TBI of 10 cGy/fraction, 5 fractions/week for 2–3 weeks Regimen B: TBI of 15 cGy/fraction twice a week for 5 weeks |
Thrombocytopenia in 34% | Mendenhall et al 30 | ||
| NHL | TBI of 10 cGy/fraction, 3 fractions/week, 180–220 cGy total | Average increase in grade of 2.2
(WHO) 3% grade 1 6% grade 2 |
Average increase in grade of 2.1
(WHO) 1 patient grade 3 |
Lybeert et al 31 | |
| NHL | Two cycles of TBI in 4 20 cGy fractions, 160 cGy total | <3.9x103 cells/µL in 45.7% | <100x103 cells/µL in
54.3% <50x103/µL in 73.7% 71.4% requiring platelet transfusion |
Hemoglobin <10 g/dL in 20% | Safwat et al 32 |
| Advanced NHL | Two TBI treatment schedules, 150 cGy total | Median nadir of 3.7x103 cells/µL | Median nadir of 77x103 cells/µL | Choi et al 33 | |
| Advanced lymphoma | TBI of 150 cGy total in 2–3 fractions/week | <2x103 cells/µL in 17.6% | <50x103 cells/µL in 17.6% | Hoppe et al 25 | |
| Low-grade NHL | TBI of 10 cGy/fractions, 3 fractions/week, 250 cGy total | 44% of patients developed grade 3 (WHO) toxicity and 16% grade 4 | Meerwaldt et al 23 | ||
| Advanced lymphocytic lymphoma | TBI of 10 cGy/fraction for 5 weeks, 150 cGy total | Severe or life-threatening
granulocytopenia in 73% patients One death due to infection |
Severe or life-threatening thrombocytopenia in 73% patients | Rubin et al 24 | |
| Lymphoma | TBI or HBI of 10–15 cGy/fraction, 2–3 fractions/week, 150 cGy total | Mild decrease in blood counts, none fell below normal ranges | Sakamoto et al 34 | ||
| Low grade localized follicular NHL | Two courses of 75 cGy separated by 2 weeks. Four weeks after TBI, involved areas treated with 40 Gy in 20 fractions | Granulocyte mean nadir of 3.9x103 cells/µL | Mean nadir of 124x103 cells/µL | Hemoglobin mean nadir of 13.4 g/dL | Richaud et al 35 |
| Oat cell carcinoma of the bronchus | TBI of 10 cGy/fractions, 5 fractions/week, 100 cGy total | No reported toxicity | Qasim et al 36 | ||
| HD-RT | |||||
| Head and neck, chest, or pelvis | 45–70 Gy | Leukocytes: Mean decrease of
14-15% Neutrophils: Mean decrease of 14-28% Lymphocytes: Mean decrease of 51-68% |
Zacharia et al 40 | ||
| Gynecologic malignancy | 45 Gy, whole pelvis | Grade 2 (CTCAE) leukopenia in
10.2% Grade 2 granulocytopenia in 1.9% |
Grade 2 hemoglobin toxicity in 1.2% | Brixey et al 41 | |
| Prostate or bladder | Prostate cancer: 76 Gy Bladder cancer: 60–70 Gy |
Leukocyte counts reduced by
33.02% Neutrophil counts reduced by 23.78% Lymphocyte counts reduced by 62.19% and the only parameter with greater than grade 2 (CTCAE) toxicity. 19% of patients experienced grade 3 toxicity |
Miszcyk and Majewski 42 | ||
| Testicular or ovarian | 30–40 Gy in 13–14 fractions to the pelvis and paraaortic lymph nodes | Lymphocyte decline from 2.4x103 cells/µL to 0.6x103 cells/µL | Decreased 60% from initial mean of 315x103 cells/µL to 195x103 cells/µL | Campbell et al 43 | |
| Advanced pancreatic cancer | 59.4 Gy in 1.8 Gy fractions | Grade 1 (ECOG) hematologic
toxicity in 37.7% Grade 2 in 11.3% Grade 3 in 9.4% of patients |
Cohen et al 44 | ||
| High-risk early-stage cervical cancers | 49.3 Gy in 29 fractions | Leukopenia in 58% Grade 4 granulocytopenia (SWOG) in 1 patient |
Grade 1 (SWOG) thrombocytopenia in 8% | Grade 1 or 2 (SWOG) anemia in 22% | Peters et al 45 |
| Cervical cancer | 50–50.4 Gy in 25–28 fractions of EBRT, followed by 30–36 Gy in 5–7 fractions of intracavitary brachytherapy | Grade 3 (CTCAE) or greater in 16.3% | Wang et al 46 | ||
| Breast cancer (stage 1-3) | 60–65 Gy in 30–36 days | Leukocyte decrease from
4.81x103 cells/µL to 3.4x103
cell/µL 93% of patients experienced lymphopenia |
Normal post treatment | Standish et al 47 | |
| Early-stage breast cancer | 56 Gy | Grade 1 (CTCAE) in 11 patients | Grade 1 (CTCAE) in 2 patients | Freedman et al 48 | |
| Oat cell carcinoma of the bronchus | 40 Gy in 20 fractions | Leukopenia (<3 x103 cells/µL) in 23% | Thrombocytopenia (<50 x103 cells/µL) in 23% | Qasim et al 36 | |
| Chemotherapy | |||||
| Advanced NHL | CVP (cyclophosphamide, vincristine, and prednisone) or C-MOPP | 36% hospitalized due to leukopenia or infection | Thrombocytopenia in 30% with platelet counts <50 x103 cells/µL | Choi et al 33 | |
| Advanced lymphoma | Single alkylating agent (cyclophosphamide or chlorambucil) or combination chemotherapy (CVP) | Leukopenia <2x103 cells/µL in 11.8% of single agent and 17.6% of combination group | Severe thrombocytopenia <50 x103 cells/µL | Hoppe et al 25 | |
| Low-grade NHL | CHVmP (cyclophosphamide, hydroxorubicin, adriamycin, VM-26) | Grade 3 (WHO) toxicity in 8% | Meerwaldt et al 23 | ||
| Advanced metastatic breast cancer | AC (adriamycin and cyclophosphamide), or ACMF (adriamycin, cyclophosphamide, methotrexate, and 5-fluorouracil) | 8.3% hospitalized due to
leukopenia Leukocytes <3x103 cells/µL in 87.5% <1x103 cells/µL in 31% |
Kennealy et al 52 | ||
| Recurrent glioblastoma | PAC (procarbazine, 1-(2-chloroethyl)-3- cyclohexyl-1-nitrosourea (CCNU, lomustine), and vincristine) | Grades 1-4 (WHO) leukopenia in 72.1% | Schmidt et al 53 | ||
| Taxane and hormone refractory prostate cancer | Ixabepilone or MP (mitoxantrone and prednisone) | Grade 3/4 (CTCAE) neutropenia in 54% of
ixabepilone recipients and 63% of MP
recipients 7 febrile neutropenia and one death due to neutropenic sepsis |
Rosenberg et al 54 | ||
| Metastatic breast cancer | Paclitaxel and carboplatin | Grade 3/4 (CTCAE) neutropenia in 82% | Grade 3/4 (CTCAE) thrombocytopenia in 18% | Perez et al 55 | |
| Resected bile duct cancer | Gemcitabine | Grade 4 (CTCAE) neutropenia in 13.3% | Ebata et al 56 | ||
| Follicular and mantle cell lymphoma | CHOP (cyclophosphamide, vincristine, doxorubicin, and prednisone) vs MCP (mitoxantrone, chlorambucil, and prednisone) | Grade 3/4 (WHO) leukopenia in 48% of
CHOP Granulocytopenia in 42% MCP Grade 3/4 leukopenia in 67% Granulocytopenia in 58% 3% complication due to infection |
Nickenig et al 57 | ||
| Advanced thymic carcinoma | CODE (cisplatin, vincristine, doxorubicin, and etoposide) | Some degree of leukopenia in all
patients Neutropenia most common grade 4 toxicity (CTCAE) |
Yoh et al 58 | ||
| Non-small cell lung cancer (NSCLC) | Pemetrexed or docetaxel | Grade 3/4 (CTCAE) neutropenia in 40.2%
of pemetrexed Grade 3/4 neutropenia in 5.3% of docetaxel |
Grade 3/4 (CTCAE) thrombocytopenia in less than 5% | Grade 3/4 (CTCAE) anemia in less than 5% | Hanna et al 59 |
| Hormone refractory prostate cancer | Docetaxel | Grade 3/4 (CTCAE) leukopenia in
16% Grade 3/4 neutropenia in 16% |
Grade 3/4 (CTCAE) anemia 4% | Beer et al 60 | |
| NSCLC | Gemcitabine and cisplatin | Leukopenia in 85% | Thrombocytopenia in 96% Grade 3/4 (WHO) in 59.6% |
All developed some grade of anemia | Van Zandwijk et al 61 |
| Locally advanced or metastatic pancreatic cancer | Gemcitabine and cisplatin | Leukopenia caused dose reduction in 17% and omission in 9% | Thrombocytopenia caused dose reduction in 65% and omission in 47% | Heinemann et al 62 | |
| Chemoradiation | |||||
| Craniospinal irradiation (CSI) | Vincristine with 31.5–36 Gy in 18–20 fractions | Leukopenia in 100% with 15% developing infection | Thrombocytopenia in 70% | Anemia in 95% with 25% requiring blood transfusion due to grade 2 (CTCAE) anemia | Petersson et al 64 |
| Anaplastic thyroid carcinoma | Doxorubicin and cisplatin with 40 Gy | Grade 4 (WHO) neutropenia in 70% | Grade 3/4 (WHO) thrombocytopenia in 13%, and 1 patient needed platelet transfusions | Grade 3/4 anemia in 27% causing 6 patients to require transfusion with hemoglobin | De Crevoisier et al 65 |
| Gynecologic malignancies | Various chemotherapies with 45 Gy and 9 Gy boost in 1.8 Gy fractions | Leukopenia in
53.8% Neutropenia/granulocytopenia in 15.4% Grade 4 (CTCAE) granulocytopenia and leukopenia occurred in 1 patient |
Anemia in 92.3% | Salama et al 66 | |
| Cervical cancer | Cisplatin with 45 Gy in 25 fractions. Boost dose of 50.4–59.4 Gy | Grade 1 (CTCAE) toxicities in 19.4%, grade 2 in 36.1%, and grade 3 in 27.8% | Beriwal et al 67 | ||
| Anal cancer | 5-fluorouracil (5-FU) and mitomycin-c (MMC) with 45–59.4 Gy | Grade 1–4 neutropenia in 69.2% 1 hospitalization due to neutropenia and pulmonary embolism |
Grade 1–4 thrombocytopenia in 46.2% | Grade 1–3 anemia in 76.9% Two patients needed RBC transfusions |
Milano et al 68 |
| Anal cancer | 5-fluorouracil (5-FU) and mitomycin-c (MMC) with 45–50.4 Gy | Addition of MMC to 5-FU increased hematologic toxicity from 3% to 18% | Flam et al 69 | ||
| Anal malignancies | Various chemotherapies with 54 Gy | Grade 1/2 leukopenia in
38%% Grade 3/4 leukopenia in 24% |
Grade 1/2 thrombocytopenia in
27%% Grade 3/4 thrombocytopenia in 2% |
Grade 1/2 anemia in 73%% Grade 3/4 leukopenia in 4% |
Pepek et al 70 |
| High-grade astrocytoma | Cisplatin and BCNU with 50–60 Gy in 17 fractions | Leukopenia in 40–77% Leukopenia <1.0 x103 cells/µL in 8–38% |
Thrombocytopenia in 68–89% | Anemia was frequent and commonly required transfusions | Kleinberg et al 71 |
| Bladder cancer | Gemcitabine or cisplatin with 50 Gy in 20 fractions | Grade 1-4 (CTCAE) toxicity in 87.5% | Turgeon et al 72 | ||
| Cervical cancer | Cisplatin with 50–50.4 Gy EBRT in 25–28 fractions, followed by 30–36 Gy intracavitary brachytherapy in 5–7 fractions | Grade 3/4 hematologic toxicity (CTCAE) in 62.5% | Wang et al 46 | ||
| Pancreatic cancer | 5-fluorouracil and mitomycin-c with 59.4 Gy in 1.8 Gy fractions | Grade 1–4 hematologic toxicity in 85.5% | Cohen et al 44 | ||
| Gynecologic malignancies | Various chemotherapies with 45 Gy | Grade 2 or greater leukopenia in
47.2% Neutropenia in 16.6% |
Anemia in 19.4% | Brixey et al 41 | |