Response of all 10 patients on cladribine therapy
. | A . | B . | C . | D . | E . | F . | G . | H . | I . | J . |
|---|---|---|---|---|---|---|---|---|---|---|
| Mean daily dose of cladribine mg/kg* | 0.12 | 0.12 | 0.12† | 0.12 | 0.13 | 0.10 | 0.10 | 0.13 | 0.13 | 0.10 |
| Tryptase, μg/L | ||||||||||
| Before | 120 | 34 | 200 | 100 | 497 | 270 | 224 | 170 | 92 | 163 |
| Best response | 44 | 16 | 124 | 55 | 171 | 153 | 144 | 12 | 70 | 43 |
| Urinary MH, μM/M creatinine | ||||||||||
| Before | 489 | 447 | 453 | 1478 | 4868 | 1220 | 4094 | 4652 | 6506 | 1928 |
| Best response | 166 | 96 | 125 | 269 | 340 | 537 | 880 | 248 | 184 | 124 |
| Urinary MIMA, μM/M creatinine | ||||||||||
| Before | 34.3 | 4.7 | 5.2 | 9.5 | 39.4 | 10.9 | 23.7 | 30.6 | 58.6 | NT |
| Best response | 5.1 | 1.7 | 4.1 | 7.3 | 7.5 | 10.1 | 20 | 4.3 | 2.5 | NT |
| Skin % UP | ||||||||||
| Before | > 50 | > 50 | > 50 | > 50 | 50 | 0 | 0 | 0 | > 50 | > 50 |
| Best response | < 5 | 10 | 10 | < 5 | < 5 | NA | NA | NA | < 5 | < 5 |
| Bone marrow | ||||||||||
| Before | 15% | 10% | 10% | 20% | >75% | 15% | 60% | 1%-15% | > 60% | 35% |
| Best response | 10% | 0% | 0% | < 5% | 20% | 5% | 30% | 1%-5% | Too early | < 5% |
| Main complaint | Collapse | Abd pain | Itching | Collapse | Weight loss | Fatigue | Flushes | — | Anaphylaxis | Diarrhea |
| Before | ++++ | ++++ | ++++ | ++++ | −11 kg | ++++ | +++ | — | Requiring IC | +++ |
| Best response | + | ++ | + | + | +12.5 kg | ++ | 0 | Under control | 0 | |
| Main complaint | Flushing | Bone pain | Fatigue | Diarrhea | Pancytopenia | Fever | Fatigue | — | Cardiomegaly; AF | Malabsorption |
| Before | ++++ | ++++ | ++++ | ++++ | Hb, 9.4; Thr, 117 | ++ | +++ | — | Therapy resistant | Gl mast cells |
| Best response | + | + | + | 0 | Hb, 13.6; Thr, 217 | 0 | + | Heart size decreased, AF controlled | Resolved; weight increased 10 kg | |
| Main complaint | Abd pain | Headache | Abd pain | Flushing | Fatigue | Splenomegaly | Splenomegaly | — | Fatigue | Skin symptoms |
| Before | ++++ | ++ | ++++ | ++++ | +++ | 17 cm | 17 cm | — | +++ | +++ |
| Best response | + | + | + | 0 | 0 | 16.5 cm | 15 cm | 0 | 0 | |
| Main complaint | — | — | — | — | Lymphadenopathy | — | — | — | — | Lymphadenopathy |
| Before | — | — | — | — | Paraaortic | — | — | — | — | Mesenterial |
| Best response | Resolved | Resolved | ||||||||
| Response22 | NA | NA | NA | NA | Major response | NA | Good PR | NA | NA | Major, incomplete |
| Time to best response | 9-12 mo | 6-9 mo | 6-9 mo | 6-9 mo | 6 mo | 3 mo | 3-6 mo | 3 mo | 2-3 mo | 8 mo |
| Response associated hematologic disorder | NA | NA | NA | Allogeneic SCT for MDS and pancytopenia | Normal hemogram, persistent abnormal MKC | Persistent Atypical CML with +8 | NA | Persistent atypical CML | NA | NA |
| Follow-up since end of therapy | Continuing response (+15 mo) | Continuing response (+5 mo) | Continuing response (+5 mo) | Not applicable, allogeneic SCT after 9 mo | Progression after 11 mo; 2nd response on re-treatment | Not applicable; change to IFN + Hydrea | No change | NA (only 3 cycles received) | Too early | Continuing response (+3 mo) |
| Adverse events | FUO; anemia requiring transfusion | None | None | Persistent pancytopenia requiring many transfusions | None | None | FUO; HZV; anemia requiring transfusions | Sweet syndrome/toxicodermia | None | Vena jugularis interna thrombosis |
. | A . | B . | C . | D . | E . | F . | G . | H . | I . | J . |
|---|---|---|---|---|---|---|---|---|---|---|
| Mean daily dose of cladribine mg/kg* | 0.12 | 0.12 | 0.12† | 0.12 | 0.13 | 0.10 | 0.10 | 0.13 | 0.13 | 0.10 |
| Tryptase, μg/L | ||||||||||
| Before | 120 | 34 | 200 | 100 | 497 | 270 | 224 | 170 | 92 | 163 |
| Best response | 44 | 16 | 124 | 55 | 171 | 153 | 144 | 12 | 70 | 43 |
| Urinary MH, μM/M creatinine | ||||||||||
| Before | 489 | 447 | 453 | 1478 | 4868 | 1220 | 4094 | 4652 | 6506 | 1928 |
| Best response | 166 | 96 | 125 | 269 | 340 | 537 | 880 | 248 | 184 | 124 |
| Urinary MIMA, μM/M creatinine | ||||||||||
| Before | 34.3 | 4.7 | 5.2 | 9.5 | 39.4 | 10.9 | 23.7 | 30.6 | 58.6 | NT |
| Best response | 5.1 | 1.7 | 4.1 | 7.3 | 7.5 | 10.1 | 20 | 4.3 | 2.5 | NT |
| Skin % UP | ||||||||||
| Before | > 50 | > 50 | > 50 | > 50 | 50 | 0 | 0 | 0 | > 50 | > 50 |
| Best response | < 5 | 10 | 10 | < 5 | < 5 | NA | NA | NA | < 5 | < 5 |
| Bone marrow | ||||||||||
| Before | 15% | 10% | 10% | 20% | >75% | 15% | 60% | 1%-15% | > 60% | 35% |
| Best response | 10% | 0% | 0% | < 5% | 20% | 5% | 30% | 1%-5% | Too early | < 5% |
| Main complaint | Collapse | Abd pain | Itching | Collapse | Weight loss | Fatigue | Flushes | — | Anaphylaxis | Diarrhea |
| Before | ++++ | ++++ | ++++ | ++++ | −11 kg | ++++ | +++ | — | Requiring IC | +++ |
| Best response | + | ++ | + | + | +12.5 kg | ++ | 0 | Under control | 0 | |
| Main complaint | Flushing | Bone pain | Fatigue | Diarrhea | Pancytopenia | Fever | Fatigue | — | Cardiomegaly; AF | Malabsorption |
| Before | ++++ | ++++ | ++++ | ++++ | Hb, 9.4; Thr, 117 | ++ | +++ | — | Therapy resistant | Gl mast cells |
| Best response | + | + | + | 0 | Hb, 13.6; Thr, 217 | 0 | + | Heart size decreased, AF controlled | Resolved; weight increased 10 kg | |
| Main complaint | Abd pain | Headache | Abd pain | Flushing | Fatigue | Splenomegaly | Splenomegaly | — | Fatigue | Skin symptoms |
| Before | ++++ | ++ | ++++ | ++++ | +++ | 17 cm | 17 cm | — | +++ | +++ |
| Best response | + | + | + | 0 | 0 | 16.5 cm | 15 cm | 0 | 0 | |
| Main complaint | — | — | — | — | Lymphadenopathy | — | — | — | — | Lymphadenopathy |
| Before | — | — | — | — | Paraaortic | — | — | — | — | Mesenterial |
| Best response | Resolved | Resolved | ||||||||
| Response22 | NA | NA | NA | NA | Major response | NA | Good PR | NA | NA | Major, incomplete |
| Time to best response | 9-12 mo | 6-9 mo | 6-9 mo | 6-9 mo | 6 mo | 3 mo | 3-6 mo | 3 mo | 2-3 mo | 8 mo |
| Response associated hematologic disorder | NA | NA | NA | Allogeneic SCT for MDS and pancytopenia | Normal hemogram, persistent abnormal MKC | Persistent Atypical CML with +8 | NA | Persistent atypical CML | NA | NA |
| Follow-up since end of therapy | Continuing response (+15 mo) | Continuing response (+5 mo) | Continuing response (+5 mo) | Not applicable, allogeneic SCT after 9 mo | Progression after 11 mo; 2nd response on re-treatment | Not applicable; change to IFN + Hydrea | No change | NA (only 3 cycles received) | Too early | Continuing response (+3 mo) |
| Adverse events | FUO; anemia requiring transfusion | None | None | Persistent pancytopenia requiring many transfusions | None | None | FUO; HZV; anemia requiring transfusions | Sweet syndrome/toxicodermia | None | Vena jugularis interna thrombosis |
MH indicates N-methylhistamine; MIMA, N-methylimidazoleacetic acid; %UP, percentage of body covered with urticaria pigmentosa; Abd, abdominal; IC, intensive care continuous monitoring; Thr, thrombocytes; AF, uncontrollable atrial fibrillation, finally requiring amiodarone; NA, not applicable (response criteria can only be applied to ASM patients); SCT, stem cell transplantation; MDS, myelodysplastic syndrome; MKC, megakaryocytes; CML, chronic myeloid leukemia; +8, trisomy 8; IFN, interferon-alpha; Hydrea, hydroxyurea; FUO, fever of unknown origin; HZV, herpes zoster varicella; and—, not applicable.
Cladribine was given in 6 cycles of 5 days each; per day 0.10 to 0.13 mg/kg was administered.
This patient had a weight of 135 kg. The dose was calculated for a body weight of 100 kg.