Summary of the patients and mice analyzed for this study
Patient . | Disease Status . | No. Mice Injected . | No. Mice Developing Disease Symptoms* . | Latency† (Days ± SD) . | Evidence of MM Engraftment . | No. of Mice With at Least One Indication of MM Engraftment . | |||
---|---|---|---|---|---|---|---|---|---|
Human Cells (FACS) . | Histology . | Bone Lesions (X-ray) . | PatientSpecific RT-PCR . | ||||||
A. Peripheral Tissue | |||||||||
Patient 1 | Aggressive | 33 | 21/33‡ | 131 ± 62 | 17/24 | 12/17 | 13/16 | 12/15 | 30/33 |
Patient 2 | Aggressive | 5 | 5/5 | 110 ± 65 | 3/5 | 1/3 | 3/5 | 3/5 | 5/5 |
Patient 3 | Aggressive | 2 | 2/2 | 60, 120 | ND | 0/2 | 1/2 | NA | 1/2 |
Patient 4 | Aggressive | 5 | 3/5 | 63 ± 21 | 0/1 | 0/4 | 1/3 | 3/4 | 3/5 |
Patient 5 | Aggressive | 3 | 3/3 | 75 ± 1 | 3/3 | 3/3 | 3/3 | 3/3 | 3/3 |
B. G-CSF mobilized blood | |||||||||
Patient 6 | Minimal | 7 | 4/7 | 103 ± 46 | 0/1 | 0/4 | 4/7 | 0/7 | 4/7 |
Patient 7 | Minimal | 5 | 0/5 | 1/1 | 0/4 | 2/4 | 1/4 | 3/5 | |
Patient 8 | Minimal | 3 | 0/3 | 0/1 | 0/3 | ND | NA | 0/3 | |
Patient 9 | Minimal | 13 | 3/132-153 | NT | ND | 0/13 | 2/6 | 7/13 | 9/13 |
Patient 10 | Minimal | 3 | 2/3 | 42, 140 | 0/2 | 0/2 | 2/3 | 0/3 | 2/3 |
Patient 11 | Minimal | 6 | 0/6 | 0/5 | 0/6 | 3/4 | 0/6 | 3/6 | |
Patient 12 | Minimal | 3 | 3/3 | 157 ± 20 | ND | 0/3 | 1/2 | 2/2 | 2/3 |
C. Secondary transfers | 6 | 2/6 | 77, 71 | 1/1 | 1/1 | 3/6 | 4/6 | 4/6 | |
D. Total number of injected mice assayed for the indicated property | 46/88 | 44 | 65 | 61 | 68 | 65/94 |
Patient . | Disease Status . | No. Mice Injected . | No. Mice Developing Disease Symptoms* . | Latency† (Days ± SD) . | Evidence of MM Engraftment . | No. of Mice With at Least One Indication of MM Engraftment . | |||
---|---|---|---|---|---|---|---|---|---|
Human Cells (FACS) . | Histology . | Bone Lesions (X-ray) . | PatientSpecific RT-PCR . | ||||||
A. Peripheral Tissue | |||||||||
Patient 1 | Aggressive | 33 | 21/33‡ | 131 ± 62 | 17/24 | 12/17 | 13/16 | 12/15 | 30/33 |
Patient 2 | Aggressive | 5 | 5/5 | 110 ± 65 | 3/5 | 1/3 | 3/5 | 3/5 | 5/5 |
Patient 3 | Aggressive | 2 | 2/2 | 60, 120 | ND | 0/2 | 1/2 | NA | 1/2 |
Patient 4 | Aggressive | 5 | 3/5 | 63 ± 21 | 0/1 | 0/4 | 1/3 | 3/4 | 3/5 |
Patient 5 | Aggressive | 3 | 3/3 | 75 ± 1 | 3/3 | 3/3 | 3/3 | 3/3 | 3/3 |
B. G-CSF mobilized blood | |||||||||
Patient 6 | Minimal | 7 | 4/7 | 103 ± 46 | 0/1 | 0/4 | 4/7 | 0/7 | 4/7 |
Patient 7 | Minimal | 5 | 0/5 | 1/1 | 0/4 | 2/4 | 1/4 | 3/5 | |
Patient 8 | Minimal | 3 | 0/3 | 0/1 | 0/3 | ND | NA | 0/3 | |
Patient 9 | Minimal | 13 | 3/132-153 | NT | ND | 0/13 | 2/6 | 7/13 | 9/13 |
Patient 10 | Minimal | 3 | 2/3 | 42, 140 | 0/2 | 0/2 | 2/3 | 0/3 | 2/3 |
Patient 11 | Minimal | 6 | 0/6 | 0/5 | 0/6 | 3/4 | 0/6 | 3/6 | |
Patient 12 | Minimal | 3 | 3/3 | 157 ± 20 | ND | 0/3 | 1/2 | 2/2 | 2/3 |
C. Secondary transfers | 6 | 2/6 | 77, 71 | 1/1 | 1/1 | 3/6 | 4/6 | 4/6 | |
D. Total number of injected mice assayed for the indicated property | 46/88 | 44 | 65 | 61 | 68 | 65/94 |
Disease symptoms, referred to in the text as end stage disease, which required that the animals be killed for humanitarian reasons, included hunched posture, ruffled coat, failure to eat and drink normally, lethargy, and sometimes hind limb paralysis. Other evidence of disease was also detected on autopsy, including visible tumor masses and/or easily fractured bones and/or white bone marrow.
Latency indicates the mean number of days within which injected animals exhibited symptoms of physical distress. It does not include those animals which died in less than 21 days after injection (a total of 17 mice), presumably of radiation-induced death; however, these animals were included in tests for human cells, bone lesions or clonotypic cells. A total of 10 mice, nearly all from the groups injected with G-CSF mobilized blood cells, were found to have engrafted human cells as identified by β2 microglobulin transcripts and/or by the presence of Ig VDJ transcripts detected using consensus primers to FR2/Jh, but had no detectable clonotypic transcripts in patient-specific RT-PCR assays.
ND = not done, NT = not tested, NA = clonotypic sequence not available.
Of 33 mice injected, 22 received IV, 6 IC, and 5 IO injections. Seven of the IV-injected mice died within the first 2 weeks and are not included among those that became sickly after injection. Fourteen of 15 IV-injected, 5 of 6 IC-injected, and all 5 IO-injected mice became symptomatic. Latency was calculated as the aggregate mean for all 3 groups.
Values for each injection type are given in results.
For this patient, all the mice were killed for experimental reasons between 1 to 3 months after injection, before exhibiting any symptoms.