Efficacy of Online Multi-Player Versus Single-Player Exergames on Adherence Behaviors Among Children: A Nonrandomized Control Trial.

Background: Exergames have the potential to significantly increase physical activity in children. Studies to date have shown mixed results and often rely on self-reported data. Multi-player gaming may augment participation. Purpose: The purpose of the study was to examine children's adherence behaviors in multi-player online exergames compared to a single-player condition within a home environment. Methods: Seventy-two children, aged 9-12 years, who were not meeting physical activity guidelines at baseline, were allocated to the multi-player or single-player condition. Six-week cycle-based exergaming trials took place 5 day/week in the early evening with online game supervision. Bike use was objectively recorded via game logs. Results: Adherence was high throughout the trial. Play session duration was M = 37.65 (SD = 15.39) min/day, and overall play duration was M = 133.45 (SD = 81.27) min in Week 1 and M = 77.23 (SD = 84.09) min in Week 6. Total physical activity was significantly higher at 6 weeks compared to baseline (p = .01, ηp2 = .13). There was no significant difference in play duration between conditions (p = .57, ηp2 = .01). Conclusion: This trial objectively demonstrated that exergames can promote high adherence levels. Multi-player capabilities did not augment adherence levels. Introducing new games throughout the trial may have motivated participants to keep playing, regardless of whether play was against real or artificial opponents. Weekly play duration decreased due to a significant drop in play frequency. For children who enjoy exergames, innovative solutions to promote more frequent exergame play are needed. Clinical This Registration: NCT02032667.

Effects of home-based exergaming on child social cognition and subsequent prediction of behavior.

The use of exergames may be one viable way to increase child physical activity, but investigation of its effects on motivation over time and prediction of adherence have seen little research attention. The purpose of this study was to compare the effect of two cycling exergame interventions (single-player, multi-player) among children aged 9-12 years on motivational variables (theory of planned behavior) and to explore whether these variables could predict objective assessment of playtime across 6 weeks. Sixty-nine insufficiently active children were recruited through advertisements within the community/schools and randomized to either the single play condition (n = 30) or multi-player condition (n = 39). Exergaming use was recorded objectively via game logs and motivational variables were assessed after a familiarization session, at 2 weeks, and at 4 weeks. Participants played the exergames M = 133.45 (SD = 81.27) minutes in week 1 to M = 77.23 (SD = 84.09) minutes in week 6. The two exergame conditions did not result in differences among theory of planned behavior variables (P > .05). Mean levels of these constructs declined across the first 4 weeks (P < .05), with the exception of injunctive norm. Positive bivariate associations (P < .05) between game play and perceived control (0-6 weeks), and intention (weeks 3-4 and weeks 5-6) were identified, but only affective attitude (assessed at week 2) predicted (P < .05) game play (3-4 weeks) in a multivariate examination of the theory of planned behavior model. The results demonstrate that social cognitive motives wane across time when exposed to repeated exergame play.

Variants of unknown significance in BRCA testing: impact on risk perception, worry, prevention and counseling.

BACKGROUND: Sequence-based BRCA testing can identify variants of unknown significance (VUS). Relatively little is known about how well a test outcome of VUS is understood by patients and referring physicians, and whether genetic counselors have an interest in the development of VUS management guidelines. DESIGN: Self-administered questionnaires were completed by 36 VUS counselees, 75 women with a BRCA mutation and 33 with no mutation found (NMF). We also surveyed 24 genetic counselors and 22 referring family physicians. RESULTS: One-third of VUS failed to recall the clinical significance of their result. Incorrect recall was significantly higher among VUS with high-school-only education (70% versus 19%, P = 0.02). Risk perception, cancer worry and uptake of surveillance and risk-reducing surgeries among VUS counselees were more similar to NMF than to mutation carriers. Genetic counselors accurately predicted the difficulties counselees would have with a VUS result and identified the need for VUS management guidelines. Referring physicians unanimously stated that genetic testing was indicated for unaffected siblings of VUS carriers. CONCLUSIONS: While VUS seems to be correctly perceived by counselees as more similar to NMF than to a pathogenic mutation, miscomprehension of VUS is more common, particularly in counselees with lower education. VUS-related educational interventions for both VUS counselees and their referring physicians are needed. We encourage the development of national VUS-related guidelines for genetic counselors.

Inpatient Exergames for Children with Cerebral Palsy following Lower Extremity Orthopedic Surgery: A Feasibility Study.

Objective: Evaluate the feasibility of implementing cycling-based exergames for children with cerebral palsy (CP) following lower extremity orthopedic surgery and explore its impact on pain and well-being.Methods: Ten children with CP were recruited; the first five received physiotherapy (comparison) and next five received fifteen exergame sessions over 3 weeks and physiotherapy (case) (NCT0376907). Feasibility indicators evaluated recruitment, questionnaire and exergame completion. Faces Pain Scale-Revised (FPS-R), PROMIS Pediatric Pain Interference Scale (PPIS), and KIDSCREEN-27 were administered. Wilcoxon signed-rank and effect size (r) tests evaluated within-group differences and between-group differences were assessed using Mann-Whitney U tests.Results: All feasibility indicators were met. Large effects for improved case group pain were identified (FPS-R r = 0.60, PPIS r = 0.58), as well as significant improvement in KIDSCREEN-27 total (U = 0.50, p = .05) and psychological well-being (U = 3.00, p = .01) scores, favoring the case group.Conclusions: Incorporating pediatric exergames is feasible and demonstrates potential for improving pain and well-being.

Canine cyclic neutropenia. A stem cell defect.

Two normal collie dogs were given 1,200 R total body irradiation followed by successful marrow grafts from their grey collie littermates with cyclic hematopoiesis. During observation periods of 97 and 41 days after grafting, both previously normal recipients showed regular cyclic fluctuations of their granulocyte and reticulocyte counts similar to those observed in their donors. These findings suggest that canine cyclic neutropenia is due to a defect in the marrow stem cell.

Balancing for Gross Motor Ability in Exergaming Between Youth with Cerebral Palsy at Gross Motor Function Classification System Levels II and III.

OBJECTIVE: To test how three custom-built balancing algorithms minimize differences in game success, time above 40% heart rate reserve (HRR), and enjoyment between youth with cerebral palsy (CP) who have different gross motor function capabilities. Youth at Gross Motor Function Classification System (GMFCS) level II (unassisted walking) and level III (mobility aids needed for walking) competed in a cycling-based exercise video game that tested three balancing algorithms. MATERIALS AND METHODS: Three algorithms: a control (generic-balancing [GB]), a constant non-person specific (One-Speed-For-All [OSFA]), and a person-specific (Target-Cadence [TC]) algorithms were built. In this prospective repeated measures intervention trial with randomized and blinded algorithm assignment, 10 youth with CP aged 10-16 years (X ± standard deviation = 12.4 ± 1.8 years; GMFCS level II n = 4, III n = 6) played six exergaming sessions using each of the three algorithms. Outcomes included game success as measured by a normalized game score, time above 40% HRR, and enjoyment. RESULTS: The TC algorithm balanced game success between GMFCS levels similarly to GB (P = 0.11) and OSFA (P = 0.41). TC showed poorer balancing in time above 40% HRR compared to GB (P = 0.02) and OSFA (P = 0.02). Enjoyment ratings were high (6.4 ± 0.7/7) and consistent between all algorithms (TC vs. GB: P = 0.80 and TC vs. OSFA: P = 0.19). CONCLUSION: TC shows promise in balancing game success and enjoyment but improvements are needed to balance between GMFCS levels for cardiovascular exercise.

Ability-Based Balancing Using the Gross Motor Function Measure in Exergaming for Youth with Cerebral Palsy.

OBJECTIVE: To test if the gross motor function measure (GMFM) could be used to improve game balancing allowing youth with cerebral palsy (CP) with different physical abilities to play a cycling-based exercise videogame together. Our secondary objective determined if exergaming with the GMFM Ability-Based algorithm was enjoyable. MATERIALS AND METHODS: Eight youth with CP, 8-14 years of age, GMFM scores between 25.2% and 87.4% (evenly distributed between Gross Motor Function Classification System levels II and III), competed against each other in head-to-head races, totaling 28 unique race dyads. Dyads raced three times, each with a different method of minimizing the distance between participants (three balancing algorithms). This was a prospective repeated measures intervention trial with randomized and blinded algorithm assignment. The GMFM Ability-Based algorithm was developed using a least squares linear regression between the players' GMFM score and cycling cadence. Our primary outcome was dyad spread or average distance between players. The GMFM Ability-based algorithm was compared with a control algorithm (No-Balancing), and an idealized algorithm (one-speed-for-all [OSFA]). After each race, participants were asked "Was that game fun?" and "Was that game fair?" using a five-point Likert scale. RESULTS: Participants pedaled quickly enough to elevate their heart rate to an average of 120 ± 8 beats per minute while playing. Dyad spread was lower when using GMFM Ability-Based balancing (4.6 ± 4.2) compared with No-Balancing (11.9 ± 6.8) (P < 0.001). When using OSFA balancing, dyad spread was (1.6 ± 0.9), lower than both GMFM Ability-Based (P = 0.006) and No-Balancing (P < 0.001). Cycling cadence positively correlated to GMFM, equal to 0.58 (GMFM) +33.29 (R2adj= 0.662, P = 0.004). Participants rated the games a median score 4/5 for both questions: "was that game fun?" and "was that game fair?." CONCLUSION: The GMFM Ability-Based balancing decreased dyad spread while requiring participants to pedal quickly, facilitating interaction and physical activity.

Total body irradiation and autologous marrow transplantation as consolidation therapy for spontaneous canine lymphoma in remission.

Seventeen dogs with spontaneous generalized lymphoma in complete clinical remission induced with combination chemotherapy were given 1100 R total body irradiation (TBI) and autologous marrow grafts as consolidation therapy. Marrow was obtained immediately before TBI, stored at 4 degrees C, and infused immediately after TBI. Two dogs died because of failure to regain adequate marrow function, 8 died after developing recurrent lymphoma and 2 died of miscellaneous causes. Five dogs are alive in unmaintained complete clinical remission 200-663 days after initiation of chemotherapy. In a comparable group of 8 dogs in complete remission after combination chemotherapy but not given consolidation therapy, none remained in remission beyond 113 days. These results indicate that high dose TBI in conjunction with autologous marrow grafting results in prolonged remission duration in dogs with spontaneous lymphoma.

Erythropoietic reserve in marrow-transplanted dogs.

The effect of marrow transplantation on erythropoiesis was studied in three normal dogs (T0), three irradiated dogs receiving compatible marrow (T1), and three irradiated dogs (T2) who donated their marrow to a recipient animal and then at a later date underwent a marrow transplant from the initial marrow recipient. Plasma iron turnover was measured (a) under basal conditions, (b) after plasma iron was elevated by iron infusion, and (c) after hemolytic anemia had been produced by phenylhydrazine. Basal plasma iron turnover in T0, T1, and T2 animals averaged 1.3, 1.0, and 1.3 mg/dl whole blood/day. Turnover of the three groups increased to 7.1, 6.2, and 6.4 mg/dl whole blood/day after the induction of anemia by phenylhydrazine. These values were converted from the transferrin saturation present at the time of the measurement to the calculated turnover at 100% saturation, thereby expressing the maximum capacity of tissues to assimilate iron. After this correction, the calculated maximum uptake was shown to be increased over basal by 3.7, 4.0, and 3.8 times. To validate this approach, an additional comparison was made between baseline turnovers at elevated levels of plasma iron and anemic animals at similarly elevated plasma iron levels. The increment of the three groups was shown to be 3.7, 3.9, and 4.0 times basal. These studies illustrate the use of a refined method of ferrokinetic evaluation of erythropoiesis and indicate that the proliferative reserve in transplanted animals is unimpaired.

Transfusion of autologous cytotoxic cells leads to failure of unrelated, DLA-nonidentical marrow grafts.

Dogs conditioned with 9.2 Gy total body irradiation (TBI) and given histoincompatible marrow transplants have a high rate of graft failure. Engraftment can be achieved by using 18 Gy fractionated TBI as preparative regimen. In this study, we tested the effects of infusing, at the time of histoincompatible marrow transplantation, autologous cells that had been stored before beginning high-dose (18 Gy) TBI. Our aim was to identify the peripheral blood mononuclear cells (PBMC) that contribute to failure of marrow grafts. Marrow graft failure was observed in three of three dogs receiving a mean of 2.1 x 10(8) unfractionated autologous PBMC/kg body weight as well as in two of two dogs receiving a mean dose of 0.075 x 10(8) PBMC/kg. When the dose of PBMC was decreased to 0.01 x 10(8)/kg, engraftment was seen in two of two dogs. These experiments thus established a cell dose response for causing marrow graft failure; further studies evaluated which subset of cells mediated this effect. Infusion of 0.09 x 10(8) nylon wool-nonadherent, plastic-nonadherent PBMC/kg was effective in causing marrow graft failure in three of three dogs. In contrast, infusion of 0.03 x 10(8) autologous monocytes/kg, enriched threefold above the number contained in the lower dose of PBMC causing graft failure, was associated with engraftment in four of six dogs. Infusion of 0.13 x 10(8) PBMC/kg treated with L-leucyl-L-leucine methyl ester (Leu-Leu-OMe), a drug that depletes canine cytotoxic T-lymphocytes (CTL), natural killer (NK) cells, and monocytes, permitted engraftment in three of four dogs. These data suggest that cytotoxic lymphocytes mediate failure of histoincompatible marrow grafts.

Stimulation of canine hematopoiesis by recombinant human granulocyte-macrophage colony-stimulating factor.

The effect of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on canine hematopoiesis was evaluated. rhGM-CSF stimulated granulocyte-macrophage colony formation of canine marrow depleted of accessory cells up to tenfold. Stimulation of colony formation was abrogated by anti-rhGM-CSF antiserum or heat inactivation. rhGM-CSF also stimulated in vivo canine hematopoiesis both when given as continuous i.v. infusion and as intermittent s.c. injections. Neutrophil, monocyte, and lymphocyte counts were increased three- to eightfold above controls, whereas values for eosinophils, reticulocytes, and hematocrits were not changed. Bone marrow histology after 2 weeks of treatment with rhGM-CSF showed hypercellularity with myeloid hyperplasia and left-shifted granulocytopoiesis. After discontinuation of rhGM-CSF, peripheral leukocyte counts returned to control level within 3-7 days. Platelet counts decreased rapidly after starting rhGM-CSF, to 5000-15,000 platelets/mm3, and increased within 24 h after stopping rhGM-CSF treatment, whereas marrow histology after 2 weeks of rhGM-CSF application showed the normal number and morphology of megakaryocytes.

Treatment of canine malignancies by 1200 R total body irradiation and autologous marrow grafts.

Twenty-five dogs with malignant lymphoma (L) and 18 dogs with solid, nonhematologic tumors (ST) were treated with 1200 R total body irradiation (TBI). Rescue from the otherwise lethal hemopoietic toxicity by infusion of autologous marrow aspirated before TBI was attempted, and survival, response to TBI, and immune reactivity post-grafting were determined. Eight L dogs survived more than 14 days post TBI and marrow grafting, and 12 out of 19 evaluable dogs showed a decrease of 75 per cent or more in clinically detectable tumor. There was no evident relationship between clinical status or marrow status before TBI and survival of more than 14 days or tumor response to TBI. Seven of the 8 survivors ultimately developed recurrent tumor. Eight ST dogs survived more than 14 days. Only 4 of 14 evaluable ST dogs showed significant clinical response of their tumor to TBI. Humoral and cellular immune reactivity were significantly impaired during the 10-week period following TBI and marrow grafting in all dogs studied. These results indicate that therapy in addition to lethal doses of TBI is necessary to cure spontaneous L or to significantly affect ST in dogs. They also provide baseline data which are necessary to assess the immunotherapeutic effectiveness of allogeneic marrow grafts.

Effect of recombinant canine stem cell factor, a c-kit ligand, on hematopoietic recovery after DLA-identical littermate marrow transplants in dogs.

We studied the effect of recombinant canine stem cell factor (rcSCF) on hematopoietic recovery, incidence of graft failure, graft-vs.-host disease (GVHD), and survival after marrow transplantation from dog leukocyte antigen (DLA)-identical canine littermates. Ten animals received 100 microg rcSCF/kg/day b.i.d. by subcutaneous injection on days 1 through 10 after 920 cGy total body irradiation and transplantation of a mean of 3.7x10(8) marrow cells/kg body weight. None of the dogs received GVHD prophylaxis. All animals showed hematopoietic engraftment. The median number of days to achieve 1000 neutrophils/mm3 was 9; 100 monocytes/mm3 were reached after 15 days, 500 lymphocytes/mm3 after 21 days, and 20,000 platelets/mm3 after 16 days. One animal developed GVHD involving skin, gut, and liver and died of bacterial pneumonia 21 days after transplantation. The remaining nine dogs were observed for a median of 37 days (range 29-84 days) posttransplantation until they were killed. Facial edema was seen in three dogs during the first 2-3 days of rcSCF administration. These results show that within the limits of this study it appears to be safe to administer SCF after DLA-identical littermate marrow transplants in dogs. Comparison with previously published data in the same model showed that neutrophil and monocyte recovery was significantly faster in dogs receiving SCF treatment compared with dogs without growth factor treatment (recovery to achieve 1000 neutrophils/mm3: median 9 days vs. 13 days, p = 0.002; recovery to 100 monocytes/mm3: median 15 days vs. 105 days, p = 0.0002). Otherwise, no significant differences were seen. Results obtained with SCF treatment were similar to those previously obtained in the same model with recombinant human granulocyte colony-stimulating factor (rhG-CSF) treatment except that recovery of lymphocytes to 500/mm3 appeared to be more rapid in G-CSF-treated dogs (median 15 days vs. 21 days, p = 0.03).

Effect of reperfusion on myocardial infarct, and the accuracy of estimating infarct size from serum creatine phosphokinase in the dog.

This study was designed to determine the effect of coronary reperfusion on (1) myocardial infarct size and (2) the accuracy of previously reported methods for estimation of infarct size serum creatine phosphokinase (CPK) values. Thirty mongrel dogs, chronically prepared, were studied in the awake state, and were divided into four groups according to the period or left circumflex coronary artery (LCCA) occlusion. Group 1: permanent occlusion (24 h) in nine dogs; group 2: 45 min occlusion (eight dogs); group 3: 1 h occlusion (five dogs); and group 4: 3 h occlusion (eight dogs). Serial blood samples were drawn for 24 h following the beginning of occlusion and were used to determine total and isoenzyme levels of CPK, and lactic dehydrogenase isoenzymes. All dogs were sacrified 24 h after the beginning of occlusion and were anatomically examined. The extent of anatomical myocardial infarction was determined and compared with the extent of myocardial infarction as estimated from serial serum CPK values. Total serum CPK increased significantly in all groups and was associated with the appearance of CPK-MB isoenzyme and an increase in LDH1,2 (LDH1 greater than LDH2) in most dogs. Total serum CPK increased within an hour after reperfusion and the mean values in groups 2, 3, and 4 were significantly high (P less than 0.05) than serum CPK values in group 1 in the period from 110 min to 4 after occlusion. These data demonstrate that reperfusion after 45 min to 3 h of coronary occlusion results in an earlier appearance of total serum CPK. The anatomical infarction in group 1 averaged 28% +/- 3% (SEM) of the total heart and was significantly larger than infarct size in all groups with reperfusion. In contrast, estimated infarction calculated from total CPK in group 1 was not significantly different from the reperfused groups. Although there was correlation between estimated and anatomical infarction, the data in each group showed that anatomical infarct size could not be accurately estimated from total serum CPK.

Single dose or fractionated total body irradiation and autologous marrow transplantation in dogs: effects of exposure rate, fraction size, and fractionation interval on acute and delayed toxicity.

Dogs were given single dose or fractionated total body irradiation (TBI) and autologous marrow grafts to prevent death from myelosuppression. Acute and delayed non-marrow toxicities were compared. Fifty-six dogs were given single dose TBI at 2.1 (n = 13), 5 (n = 12), 10 (n = 15), or 20 (n = 16) cGy/min. Acute radiation toxicity and mortality was related to the exposure rate; radiation doses resulting in 50% mortality at 7 days (LD 50/7) at 2.1, 5, 10 and 20 cGy/min were 1,692, 1,499, 1,261, and 1,056 cGy respectively. Fifty-three dogs were given fractionated TBI, 200 cGy three times a day with 6-hour intervals at 2.1 (n = 13), 5 (n = 9), 10 (n = 13), or 20 (n = 18) cGy/min. The LD 50/7 at the four exposure rates were 1,628, 1,470, 1,184, and 1,320 respectively. Thus, for exposure rates of 2.1, 5, and 10 cGy/min, the tolerated doses were comparable for single dose and fractionated TBI. At 20 cGy/min dose fractionation appeared to offer some advantage, although this fractionation effect in part may have been due to random variation with small numbers of dog treated. Following recovery from the immediate TBI-related toxicity, eight dogs given single dose and four dogs given fractionated TBI died, generally from infections, 8-30 days following transplantation. There was a striking difference in regards to long-term survival dependent upon the TBI regimen. Among dogs given greater than or equal to 1,000 cGy of TBI and alive 30 days after transplant only 1 of 18 given single dose TBI became a long-term survivor compared to 19 of 22 given fractionated TBI. Causes of death included pancreatic fibrosis, malnutrition, hepatic failure, and a generalized wasting syndrome. All 5 dogs given a single dose of 800 cGy (at 20 cGy/min) became long-term survivors. Fourteen dogs were given increments of 150 cGy at 7 cGy/min every 3 hours for total doses of 1,500-2,400 cGy. The LD 50/7 was approximately 1,900 cGy. All 6 dogs alive at 30 days became healthy long-term survivors. Four dogs were given increments of 600 cGy at 2.1 cGy/min every 48 hours for a total dose of 1,800 cGy. All 4 dogs became long-term survivors. In conclusion, exposure rate and total dose are the most important parameters for acute toxicity associated with TBI. The effect of dose fractionation is minimal at low exposure rates and appears to be dependent also upon increment size and fractionation interval.(ABSTRACT TRUNCATED AT 400 WORDS)

Marrow grafts between DLA-identical and homozygous unrelated dogs: evidence for an additional locus involved in graft-versus-host disease.

Marrow transplants were carried out between unrelated donor-recipient pairs of dogs that were homozygous and identical for DLA-A, B, C, and D, i.e., mutually nonreactive in mixed leukocyte culture. Recipients were conditioned for transplantation by 1,200 R of total body irradiation and then treated with intermittent methotrexate for 102 days in order to prevent or delay graft-versus-host disease (GVHD). Of 13 dogs that received transplants, 4 are surviving with good grafts and no GVHD for more than 12 to 20 minutes. Nine died, 6 with GVHD between days 26 and 141, 1 with wasting on day 65, 1 with interstitial pneumonia on day 83, and 1 with graft rejection on day 23. In comparison, the survival of 17 DLA-identical littermates treated in the same manner was significantly better with 16 surviving without GVHD (P less than 0.01), while the survival of 54 DLA-nonidentical littermates was significantly worse with only two surviving without GVHD (P less than 0.025). These results are incompatible with the concept that solely the loci detected by mixed leukocyte culture and serotyping are responsible for GVHD. One or more additional loci appear to be involved. Knowledg e of this locus (loci) is important if marrow grafting between unrelated individuals is to be successful. However, results also indicate that an unrelated "compatible" marrow graft is more likely to succeed than a graft from an incompatible littermate.

Cure of malignant lymphoma in dogs with peripheral blood stem cell transplantation.

Twelve dogs with spontaneous malignant lymphoma in chemotherapy-induced remission were treated with total-body irradiation (TBI) and transplantation of autologous peripheral blood mononuclear cells collected following chemotherapy-induced expansion of the stem cell pool. Four animals (33%) died of transplant-related complications, five (41%) relapsed, and three (25%) are long-term disease-free survivors. Recovery to 1000 white cells/mm3 occurred by day 16 and dogs no longer required platelet transfusions by day 37. With the exception of delayed platelet recovery these results are virtually identical to those previously reported using autologous bone marrow transplantation for canine lymphoma. This study therefore suggests that autologous peripheral blood mononuclear cells collected following chemotherapy-induced expansion of the stem cell pool may offer a realistic alternative to autologous marrow transplantation in patients with malignant lymphoma for whom autologous marrow is not available.

Effect of time on sensitization to hemophoietic grafts by preceding blood transfusion.

Previous studies have shown that a single transfusion with whole blood from the intended marrow donor 10 days before 1,200 R of total body irradiation (TBI) and marrow grafting can immunize a dog and lead to rejection of the subsequent marrow graft. The present study explored the effect of time on immunization to marrow grafts by preceding blood transfusion. All receipents were given 1,200 R of TBI followed with 4 hr by a hemopoietic graft from an unrelated donor mismatched at the major canine histocompatibility complex. Two groups of recipients were studed. In group 1, 7 dogs were given a transfusion of blood from the marrow donor 24 hr before TBI, and 6 rejected the graft; in group 2, 16 dogs were given transfusion of blood from the marrow donor 3 months before TBI, and 8 rejected the graft. The frequency of rejection in both groups was significantly greater than in untransfused dogs mismatched with their donors at the canine major histocompatibility complex (11 rejections in 67 transplants). The results indicate that exposure to donor blood from 24 hr to 3 months before marrow grafting significantly increases the likelihood of graft rejection.

Effect of trimethoprim-sulfamethoxazole on hematological recovery after total body irradiation and autologous marrow infusion in dogs.

To test the effect of the combination of trimethoprim-sulfamethoxazole (TMP-SMX) on hematological recovery after bone marrow transplantation, dogs were conditioned with 1,200 R total body irradiation and then infused with autologous marrow. Twenty dogs were given TMP-SMX at doses equivalent to 10, 20, or 40 mg TMP/kg/day beginning on the day of marrow infusion and continued until the granulocyte count reached 10(3)/mul; in addition, one-half of the dogs received methotrexate, 0.4 mg/kg on days 1, 3, 6, and 11 and then weekly until termination of the study. Granulocyte and platelet changes were compared to those of dogs given 1,200 R, autologous marrow infusion, and no TMP-SMX. Dogs given 10 and 20 mg TMP/kg/day had normal granulocyte and platelet recovery after irradiation. Dogs given 40 mg TMP/kg/day showed a significant delay in granulocyte recovery and mildly delayed platelet recovery. This suggests that TMP-SMX in prophylactic doses (5 mg TMP/kg/day) can be given safely to human patients immediately after allogeneic marrow transplantation and thus probably prevent even very early cases of Pneumocystis carinii pneumonia, and possibly bacterial infections as well.

Marrow transplant studies in dogs with malignant lymphoma.

Ninety-five dogs with spontaneous malignant lymphoma in chemotherapy-induced remission were treated with total-body irradiation (TBI) and bone marrow transplantation. Among 38 dogs treated with 8.4 Gy delivered at 4 cGy/min, 9 (24%) became long-term disease-free survivors. Ten of the 38 (26%) died of transplant-related complications and the actuarial relapse rate was approximately 65%. Forty animals were treated with higher-dose TBI (13.5 Gy). The higher-dose TBI led to an increased incidence of transplant-related deaths (55% vs. 26%) and did not reduce the actuarial relapse rate. Eight animals were treated with 8.4 Gy at 4 cGy/min, allogeneic marrow from unrelated donors, and posttransplant immunosuppression with methotrexate and cyclosporine. Of 8 animals, 6 died within 2 weeks of transplant of infection and 2 died later of graft-versus-host disease. Finally, 9 dogs were treated with 8.4 Gy at 4 cGy/min, autologous marrow, and posttransplant methotrexate and cyclosporine. Six of these animals died within 2 weeks of transplant. These studies thus demonstrated that dogs with malignant lymphoma in remission can be cured with high-dose TBI and autologous marrow transplantation, that increasing the total dose of TBI led to increased toxicity without a decrease in the relapse rate, and that post-transplant therapy with methotrexate and cyclosporine was poorly tolerated in these animals.