The RBE for skin tumors and hair follicle damage in the rat following irradiation with alpha particles and electrons

Rat skin was irradiated with cyclotron-accelerated alpha particles with doses ranging from 210 rads to 6850 rads and monoenergetic electrons with doses ranging from 810 rads to 12,300 rads. The beams were modified so that the depth-dose curves were approximately identical with penetrations of about 1.0 mm. Tumors were counted every 4 weeks for 80 weeks, and at death or sacrifice the hair follicle damage was assessed by using "whole mounts" of separated epithelium. The RBE values determined from a comparison of the dose response curves were: acute skin injury, RBE = 3.0+/-1.0; hair follicle survival, RBE = 2.1 +/- 0.7; hair follicle damage, RBE = 2.6 = 0.4; tumor induction, RBE = 2.9+/- 0.5. Within the experimental error, these values were independent of the dose. For both types of radiation, the tumor incidence increased approximately as the square of time and at low doses approximately as the 4th power of dose. The histological characteristics of the tumors and the correlation between the incidence of tumors and damaged hair follicles were independent of the type of radiation. The results were consistent with the hypothesis that structural damage to the hair follicles is a factor in the tumor induction process.     

An experimental neurovascular island skin flap for the study of the delay phenomenon.

We present an experimental neurovascular island skin flap. It is a consistent, reproducible model which produces a definite pattern of surviving skin flap area versus skin flap necrosis. There is a constant, anatomically definable nerve and vascular supply to the flap. This model permits independent experimental manipulation of the neural, arterial, and venous supply to the skin. It is useful, therefore, for the study of the vascular mechanisms of the skin microcirculation. We also demonstrated that increased flap survival can be produced by a delay involving denervation alone (leaving the vascular supply intact) or by devascularization alone (leaving the nerve supply intact). We conclude that both the adrenergic denervation and the ischemia contribute to the production of the delay phenomenon. We suggest that sustained vasodilation--vascular smooth muscle relaxation--is the vascular mechanism that accounts for the delay phenomenon.     

Pulsed magnetic fields applied to a transferred arterial loop support the rat groin composite flap

Pulsed magnetic fields have been shown to stimulate neovascularization in the authors' laboratory. The rat groin composite flap was used to create a prospective randomized trial to test the effectiveness of these pulsed magnetic fields. The skin paddle to this flap is highly consistent, and the authors proposed using the flap to study how pulsed magnetic fields affect composite flap survival when the dominant vessel to the flap is divided and flap survival becomes dependent on a transferred vessel loop. Forty-three rats had the tail artery microsurgically anastomosed to the femoral artery and placed between the groin musculature and the abdominal skin. Pulsed magnetic energy of 1 gauss was applied for 8 (n = 14) or 12 (n = 8) weeks to the experimental groups. Control groups were treated in a comparable manner for 8 (n = 16) or 12 (n = 5) weeks. After the 8 or 12 weeks, all groups had an 8 x 4-cm skin flap raised, and the superficial epigastric artery, the main feeding vessel, was ligated. After 5 days, the total area of the flap and the area of necrosis were traced onto velum paper for each rat. The percent survival was calculated per rat, and a mean survival percentage was calculated per group. The experimental animals treated with pulsed magnetic fields for 8 weeks had statistically significant improved flap survival over the control animals. The study provides evidence that pulsed magnetic energy stimulates angiogenesis and suggests a possible use of this modality to create island vascular flaps in otherwise random vascular territories.     

Metabolic adaptations in delayed skin flaps. Glucose utilization and hexokinase activity.

The distribution of glucose and hexokinase activity was determined in the epithelial tissue of delayed bipedicled skin flaps in guinea pigs. The periods of "delay" were 1, 3, 7, 14, or 21 days. The flap survival was maximal (100% of the flap) when the flap elevation was performed either 7 or 14 days following the "delay" procedure. When the flap elevation was performed 1, 3, or 21 days following the "delay" procedure, the result was partial necrosis. A differential distribution of epithelial glucose was found within the bipedicled flaps. The lowest glucose level (30% of normal) was at a distance of 2 to 3.5 cm from the end of the caudal pedicle during the first day after the "delay" procedure. This decreased glucose content recovered toward normal levels during the later part of the "delay" period. The bipedicled flaps exhibited increased hexokinase activity during the 3-week period of the "delay," and the responses of hexokinase activity and tissue glucose levels to the "delay" procedure were reciprocal in the caudal half of the flaps.     

Postoperative irradiation after reconstructive surgery: comparative study of radiosensitivity between free-skin grafts and skin flaps

Radiation effects after reconstructive surgery (free-skin grafts and skin flaps) were studied in the rat, and the optimum time for irradiation was determined. The radiosensitivity of both free-skin grafts and skin flaps showed the same trend depending on time of irradiation after operation. The grafts or flaps irradiated in the hypervascular stage showed severe reactions to irradiation, whereas those irradiated in the hypovascular stage showed milder reactions in gross and microangiographic observation. Vascular damage should be given primary consideration when deciding the proper time for irradiation after reconstructive surgery. In general, free-skin grafts showed more severe reactions than skin flaps, especially in the grafts irradiated in the early stage after operation. The experimental results of this study cannot be readily transferred to a clinical setting, but they suggest that postoperative irradiation could be begun 3 to 4 weeks after operation with respect to graft or flap survival, and the results of the clinical cases almost coincide with these experimental results.     

Improvement of survival of skin flaps by combined gene transfer of hepatocyte growth factor and prostacyclin synthase

BACKGROUND: Increasing the local blood flow is a critical factor for long-term survival of skin flaps. Thus, a molecular therapy to increase the blood flow by means of an angiogenic factor is considered to be a useful strategy to improve skin flap survival. We focused on a combined strategy to stimulate not only angiogenesis, but also vasodilation of local microvessels, using co-transfection of the hepatocyte growth factor (HGF) and prostacyclin synthase (PGIS) genes to enhance the survival of random-pattern skin flaps. METHODS AND RESULTS: A 2 x 8 cm full thickness cranial pedicled random-pattern flap was made on the back of each 12-week-old male rat. At 3 days before operation, 400 microg of human HGF and PGIS naked plasmid DNA or control plasmid was transfected into the flaps by needle-less injection using a Shima Jet, resulting in successful expression of human HGF and PGIS in the skin flaps. Transfection of both genes into the distal half of skin flaps at 3 days prior to operation significantly increased the survival rate of skin flaps, while transfection all over the flaps did not. In addition, transfection prior to operation was more effective than simultaneous treatment. Moreover, co-transfection of these genes improved the survival area of skin flaps, accompanied by an increase in blood flow of skin flaps, even in a diabetic model. CONCLUSIONS: Overall, these results indicate that combination treatment with HGF and PGIS genes by Shima Jet could be an effective strategy to improve skin flap survival.     

Curcumin treatment enhances the repair and regeneration of wounds in mice exposed to hemibody gamma-irradiation

Hemibody irradiation in multiple fractionated doses is frequently used for the treatment of various neoplastic disorders. It produces both acute and late effects on the skin and subcutaneous tissues that have profound implications in the healing of surgical wounds. Because of the crucial practical importance of hemibody radiation exposure associated with skin wounds, it is imperative to investigate the efficacy of cost-effective herbal products in the reconstruction of irradiated wounds. Therefore, the effect of pretreatment of curcumin was studied on the healing of excision wound in mice exposed to 2, 4, 6, or 8 Gy of hemibody gamma-radiation. A full-thickness skin wound was created by removing the skin flap of the dorsum of 8- to 10-week-old Swiss albino mice partially (lower half, below the rib cage) exposed to 2, 4, 6, or 8 Gy of gamma-radiation. The progression of wound contraction was monitored periodically by capturing video images of the wound, where the first image of each wound from different groups was obtained 1 day after wounding and that day was considered as day 0. Eight animals were used in each group at each exposure dose for wound contraction studies. Furthermore, the effect of curcumin on mean healing time after exposure of mice to 2, 4, 6, or 8Gy of hemibody gamma-radiation was also evaluated, where eight animals were used in each group at each exposure dose. Collagen, hexosamine, DNA, nitric oxide, and histologic profiles were also evaluated during the course of healing of excision wounds at days 4, 8, and 12 after irradiation treated or not with curcumin before exposure to 0 or 6 Gy of gamma-radiation. Six animals were used in each group at each interval for each biochemical parameter studied, except for histologic evaluations, where four animals were used in each group at each interval. Exposure of mice to different doses of gamma-radiation resulted in a dose-dependent delay in contraction and wound-healing time of excision wound, whereas curcumin pretreatment caused a significant elevation in the rate of wound contraction and a decrease in the mean wound-healing time. Treatment with curcumin before irradiation enhanced the synthesis of collagen, hexosamine, DNA, nitrite, and nitrate, and histologic assessment of wound biopsy specimens revealed improved collagen deposition and an increase in fibroblast and vascular densities. The authors' study demonstrates that curcumin pretreatment has a conducive effect on the irradiated wound and could be a substantial therapeutic strategy for ameliorating radiation-induced delay in wound repair in cases of radiation-induced skin injuries.     

Nutrient blood flow in delayed axial pattern skin flaps in pigs.

Blood flow was investigated in 112 skin flaps (84 delayed and 28 undelayed) in 28 pigs. The flow was significantly (P less than 0.001) increased over the control flow with increasing delay intervals, reaching the greatest flow at one week after the delay (paralleling the increase in tissue survival). This increased blood flow persisted after definitive flap raising. The circulatory adjustments within the first week of the delay constitute the delay phenomenon, and they determine the ultimate viability of the skin flap in this model.     

Skin-sparing mastectomy and immediate autologous tissue reconstruction after whole-breast irradiation

Traditional breast conservation therapy consists of lumpectomy and whole-breast irradiation. Local recurrence after breast conservation is usually managed with salvage mastectomy. Skin-sparing mastectomy and immediate autologous tissue reconstruction is an accepted method of managing primary breast malignancies with exceptional aesthetic results. The purpose of this study was to evaluate this technique in the previously irradiated breast. This study is a retrospective review of all patients undergoing skin-sparing mastectomy and immediate reconstruction with autologous tissue after failed breast conservation therapy between 1995 and 1999. There were 11 patients with a mean age of 45 years (range, 34 to 58 years). Initial lumpectomy was performed for ductal carcinoma in situ in six patients and infiltrating carcinoma (ductal or lobular) in five patients. The interval from lumpectomy to salvage mastectomy ranged from 12 to 169 months (mean, 44 months). Reconstructive techniques included unipedicled transverse rectus abdominis musculocutaneous (TRAM) flap (n = 4), free TRAM flap (n = 4), and latissimus flap with immediate placement of a saline implant (n = 3). Flap survival was 100 percent, and there were no early flap complications. One patient developed partial-thickness mastectomy flap loss (3 x 3 cm), which was managed conservatively. There were no instances of full-thickness mastectomy skin loss. Late complications included capsular contracture (n = 2), fat necrosis (n = 1), and ventral hernia (n = 1). There was one late death from metastatic disease; the remaining patients were without evidence of disease at a mean of 48 months (range, 30 to 75 months). Aesthetic results were judged as excellent (n = 4), good (n = 5), fair (n = 1), and poor (n = 1). These results demonstrate that skin-sparing mastectomy and immediate autologous tissue reconstruction can be safely performed in patients with previous whole-breast irradiation. Clearly, patient selection is paramount with attention to the quality of the irradiated breast skin and the anatomic location of the recurrent disease. In this experience, the best results were seen after TRAM (pedicled or free) flap reconstruction.     

Drug treatment and flap survival

Some investigators found that isoxsuprine, propranolol, or heparin would increase skin-flap survival in loose-skinned animals. We evaluated the effects of these three drugs in the pig, an animal with skin circulation similar to that of humans. Four hundred ventrally based skin flaps that have a proximal axial portion and a distal random portion were made on the flanks of 40 pigs. There were eight study groups: control, isoxsuprine preoperatively and postoperatively, propranolol preoperatively and postoperatively, isoxsuprine postoperatively only, propranolol postoperatively only, heparin, single-stage surgical delay, and two-stage surgical delay. Flap survival was improved by the two-stage surgical delay when compared with the control flaps, flaps from pigs receiving a drug, or flaps from pigs having a single-stage surgical delay (p less than 0.001). When compared with the control flaps, neither isoxsuprine, propranolol, heparin, nor single-stage surgical delay significantly increased flap survival.     

OBSERVATIONS ON THE MICROFLORA OF MINCED CHICKEN MEAT IRRADIATED WITH 4 MeV CATHODE RAYS

SUMMARY: Experiments are described in which minced chicken meat, packed anaerobically, was irradiated at room temperature and in the frozen state with a wide range of doses of 4 MeV cathode rays. Sterility was achieved in 14 out of 15 samples which had received 2 × 10⁶ rads or more. Doses of 0·5 and 1·0 × 10⁶ rads allowed survival of a few bacteria/g, usually spore formers. Bacterial counts indicated an approximately logarithmic decrease in numbers at lower doses, while freezing reduced the bactericidal effect.
The storage life at 5° was prolonged only slightly by doses of 5 × 10⁴ and 10 × 10⁴ rads, and highly variable results were obtained with 17·5 × 10⁴ rads. A dose of 25 × 10⁴ rads, however, increased the storage life very considerably. The types of bacteria present initially, and after irradiation with low doses and storage at 5°, were studied. After storage for 12 days or more various types of nonsporing Gram-positive rods were predominant in almost all samples, both control and irradiated. Streptococci were also important where irradiation with 17·5 × 10⁴ and 25 × 10⁴ rads was followed by long storage.     

Effects of ionizing radiation (60Co gamma rays) on growth and morphogenesis ofHaworthia mirabilis,haw. Callus tissue

Summary The effects of γ-radiation on growth and morphogenesis ofHaworthia callus in vitro were determined. The doses ranged from 100 to 5000 rads. Survival, growth pattern, growth rate, and differentiation of vegetative buds and roots in both irradiated and nonirradiated callus were compared. Growth data up to 24 weeks for irradiated and control cultures were analyzed. The dose range between 800 to 2500 rads produced compact callus as compared to the controls which were friable. After 12 weeks all control cultures differentiated vegetative buds with roots, whereas callus exposed to 800 to 2500 rads continued to grow with little or no organogenesis. However, it was observed that the wet and dry weights of callus receiving 1000 to 1500 rads ultimately exceeded those of nonirradiated controls.     

A new flap design: neural-island flap

This report introduces the "neural-island flap" concept, which represents a consistent and reliable skin flap design supplied only by the intrinsic vasculature of a cutaneous nerve. In this study, the lateral femoral cutaneous nerve was selected as the pedicle of the neural-island flap, and a standard skin flap, which is the territory of the accompanying vessels (i.e., iliac branches of the iliolumbar artery and vein), was elevated on the lower dorsal region of the rats. In a total of 92 Wistar rats, three experiments were performed. In part I (n = 24), the vascular anatomy of the lateral femoral cutaneous nerve was established by the methods of dissection, microangiography, nerve mapping, perfusion with colored latex and India ink, and histologic analysis. In part II (n = 46), the role of the cutaneous nerve in supporting an acutely elevated skin flap was explored by creating five flap groups as follows: group 1, conventional flap (artery, vein, and nerve intact); group 2, neural island flap (only the nerve intact); group 3, neurocutaneous flap (vein and nerve intact); group 4, denervated flap (artery and vein intact); and group 5, skin graft. In part III (n = 22), the role of a preliminary surgical delay procedure to augment the survival of the neural island flap was investigated. Results of the anatomic studies indicated a consistent perineural vasculature by the accompanying iliolumbar artery. Skin flaps survived totally in groups where the artery and vein were intact, whereas mean survival rates for the neural island flap and the neurocutaneous flap were 38.2 +/- 3.1 percent and 44.5 +/- 3.8 percent, respectively (p > 0.05). Results of part III of the experiment demonstrated a significantly higher survival for the delayed neural island flap (94.5 +/- 5.5 percent) compared with the acutely elevated neural island flap (p < 0.05). The perineural and intraneural vessels were found to be greatly dilated after a delay procedure, demonstrated by direct observation, microangiography, histologic analysis, dye injection study, and scanning electron microscopy. On the basis of this promising series of experiments, a clinical technique was developed using the sural neural-island flap. The flap was used to reconstruct lower extremity defects in four cases. A delay procedure was accomplished in the first stage by elevating a fasciocutaneous flap from the midcalf region based on a posterior skin bridge and the sural nerve. After a 2-week delay period, a sural neural-island flap was created based on the nerve and transposed to the defect. Flap survival was complete in all cases, with a satisfactory result. The authors conclude that this report proves for the first time that a robust and reliable skin flap can be created pedicled only by the intrinsic vasculature of a cutaneous nerve, after a proper surgical delay. The so-created neural-island flap design offers two novel advantages: (1) a very narrow pedicle and (2) a pedicle without any restriction to a specific pivot point, in addition to the previously described unique advantages of preservation of a major artery and avoidance of microvascular anastomoses.     

Effectiveness of hypoglycemic agents in guinea pigs exposed to mixed gamma-neutron radiations

The effect of 200, 1000, and 5000 rads of mixed gamma-neutron radiations on total blood reducing sugar and blood glucose levels in guinea pigs was investigated 2 and 24 hours, and 9, 22, and 60 days postirradiation. In addition, the effectiveness of insulin and tolbutamide in these animals was evaluated before and after irradiation. Glucose increased to a lesser degree and later than did the nonglucose fraction of the blood sugar. Insulin and tolbutamide were at least as effective in irradiated animals as in unirradiated ones except after 5000 rads, when tolbutamide was significantly less effective. These results suggest that: (1) insufficient insulin is released by the pancreas in response to elevated blood sugar levels following irradiation; (2) the pancreas does produce insulin at these times and is able to release it in response to tolbutamide; and (3) a decrease in insulin production occurs following supralethal doses of radiation.     

Wound healing in X-irradiated mammalian skin.

Certain parameters of wound healing were investigated in mouse skin given 950 rads and 3325 rads of X-irradiation at various times relative to wounding. Increased inflammation, delayed dermal regeneration, and delayed contraction were noted in all irradiated groups. The activation of surrounding hair follicles, a process that usually accompanies wounding in mouse skin, occurred earlier, over a shorter elapsed time, and over a greater area of skin in animals irradiated prior to wounding than in the controls or in those irradiated and wounded simultaneously. Epidermal mitotic activity in wounds made at the time of irradiation was initially depressed but recovered by the second postoperative day. Wounds in pre-irradiated animals gave an unexpected result. They responded with an immediate burst of mitotic activity without the usual 24-hr lag that was seen in controls. In the pre-irradiated specimens a substantial number of cells appeared to die after dividing.     

Role of nitric oxide in skin flap delay

Surgical delay of skin flaps before transfer is known to improve flap viability. This study attempts to elucidate the mechanism of vasodilation by exploring the effects of nitric oxide on the microcirculation of delayed skin flaps. Using a skin flap model in 22 CD-1 white mice, the diameter of two nonterminal choke arteries was measured using in vivo videomicroscopy. Vessel flow was also measured using an optical Doppler velocimeter. Similar measurements were recorded in several animals on the same vessels in which subcutaneous dissection without elevation was performed. Average vessel diameter ranged from 21.77 to 25.55 microm before skin flap delay. Average flow ranged from 1.72 to 2.44 nl/sec before delay. Next, each animal received an intraperitoneal dose of nitro-aminomethyl-1-arginine (L-NAME), a nitric oxide synthase inhibitor delivered by means of osmotic pump at a level of 0 (n = 13 arteries), 20 (n = 10), 50 (n = 8), or 100 mg/kg/day (n = 7). Flaps were re-elevated 72 hours later and the aforementioned measurements were repeated. Vessel diameter increased to 44.92 microm in the control (0 mg/kg L-NAME) animals. Flow increased to 7.66 nl/sec in the control animals. Vessel dilation and flow did not change significantly in the nonoperative vessels. As the dose of L-NAME increased in the treated animals, there was a significant decrease in vasodilation and flow (p = 0.015 and p = 0.03, respectively). The authors' results demonstrate that nitric oxide is an important element of vasodilation and contributor to the phenomenon of skin flap delay.     

Improved vitality of experimental random dorsal skin flaps in rats treated with enriched cell culture medium

A defined, serum-free cell culture medium supplemented with nonsteroidal anabolic hormones, insulin, thyroxin, and growth hormone was found to accelerate wound healing by stimulating vascularized granulation tissue formation, epithelialization, and angiogenesis. The aim of this work was to study the effect of cell culture medium on the survival rate of cephalically based random dorsal skin flaps in an animal model. A total of 77 Sprague-Dawley rats were randomized into five treatment groups: pharmacologic delay with cell culture medium, flap enhancement with cell culture medium, surgical delay, biological delay with saline, and control. Statistically significant differences in distal flap necrosis were found among all groups (p<0.003). The rats treated with cell culture medium before flap elevation showed a significant increase in flap viability: a survival rate of 83 percent, compared with the control group, which demonstrated a survival rate of only 58 percent (p<0.0001). The surgical delay and the groups treated with cell culture medium yielded similar results with no significant difference between them. This study indicates that preoperative injection of cell culture medium may play a role in decreasing skin flap necrosis.     

Effects of color temperature of fluorescent lamps on body temperature regulation in a moderately cold environment

A study on the effects of different color temperatures of fluorescent lamps on skin and rectal temperatures in a moderately cold environment involving (i) changes in skin temperature of 7 male subjects exposed to an ambient temperature ranging from 28 degrees C to 18 degrees C (experiment I) and (ii) changes in skin and rectal temperatures and metabolic heat production of 11 male subjects exposed to ambient temperature of 15 degrees C for 90 min (Experiment II) was conducted. In Experiment I, the reduction of mean skin temperature from the control value was significantly greater under 3000 K than under 5000 K or 7500 K lighting. In Experiment II, the reductions in mean skin temperature and rectal temperature were respectively greater and smaller under 3000 K than those under 5000 K or 7500 K lighting. However, metabolic heat production was not affected by color temperature conditions. The relationships between morphological and physiological parameters revealed that no significant relation of rectal temperature to body surface area per unit body weight was found only under 3000 K. Furthermore, while the mean skin temperature was independent on the mean skinfold thickness under 3000 K, a significant negative correlation between the rectal and mean skin temperatures was observed. Therefore, body heat loss might be suppressed effectively by increasing the vasoconstrictor tone under a color temperature of 3000 K, and the body shell was dependent only on morphological factors under 5000 K and 7500 K lighting.     

Sunless skin tanning with dihydroxyacetone delays broad-spectrum ultraviolet photocarcinogenesis in hairless mice

Sunless tanning with dihydroxyacetone (DHA) is not considered to be a sunscreen although it does absorb parts of the ultraviolet (UV) spectrum. We investigated the protection with topical application of DHA against solar UV-induced skin carcinogenesis in lightly pigmented hairless hr/hr C3H/Tif mice. Broad-spectrum UV radiation, simulating the UV part of the solar spectrum was obtained from one Philips TL12 and five Bellarium-S SA-1-12 tubes. Three groups of mice were UV-exposed four times a week to a dose-equivalent of four times the standard erythema dose (SED), without or with application of 5 or 20% DHA only twice a week. Similarly, three groups of mice were treated with DHA and irradiated with a high UV dose (8 SED), simulating a skin burn. Two groups (controls) were not irradiated, but either left untreated or treated with 20% DHA alone. The UV-induced skin pigmentation by melanogenesis could easily be distinguished from DHA-induced browning and was measured by a non-invasive, semi-quantitative method. Application of 20% DHA reduced by 63% the pigmentation produced by 4 SED, however, only by 28% the pigmentation produced by 8 SED. Furthermore, topical application of 20% DHA significantly delayed the time to appearance of the first tumor >or=1mm (P=0.0012) and the time to appearance of the third tumor (P=2 x 10(-6)) in mice irradiated with 4 SED. However, 20% DHA did not delay tumor development in mice irradiated with 8 SED. Application of 5% DHA did not influence pigmentation or photocarcinogenesis.In conclusion, this is the first study to show that the superficial skin coloring generated by frequent topical application of DHA in high concentrations may delay skin cancer development in hairless mice irradiated with moderate UV doses.     

A phase III comparison of methyl-CCNU + vincristine with or without BCG + allogeneic tumor cells in metastatic melanoma

Summary Sixty-two patients with metastatic malignant melanoma were randomized to treatment with either (a) methyl-CCNU (200 mg/m², PO every 8 weeks) plus vincristine (2 mg IV every 4 weeks), or (b) the same chemotherapy plus intradermal (ID) injections of irradiated (15,000 rads) allogeneic (fresh-frozen) melanoma cells (1–2×10⁸) admixed with BCG (Glaxo, 2–4.5×10⁶ organisms) every 2 weeks. Treatment cycles were repeated every 8 weeks until tumor progression. Seven (2 CR, 5 PR) objective remissions were noted among 31 patients (22.5%) treated with chemotherapy alone, whereas six (3 CR, 3 PR) objective remissions were noted among 31 patients (19%) treated with chemoimmunotherapy (P>0.05). The medians for remission duration (6 months) and survival (6.5 months) in the chemotherapy group did not differ significantly from the medians for remission duration (8 months) and survival (8 months) in the chemoimmunotherapy group. The patients manifested no unexpected toxicity. Hematologic toxicity was experienced by patients on both regimens; however, those receiving chemoimmunotherapy rebounded more quickly.