Lymphocyte injection therapy in treatment of lymphedema

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Lymphocyte injection therapy in treatment of lymphedema

Postby patoco » Thu Sep 28, 2006 8:11 am

Lymphocyte injection therapy in treatment of lymphedema

Lymphedema People


An experimental treatment modality that was tested in the late 1980's and
early 1990's was the injection of lymphocytes of L-selectin (+) and CD(-) into the effected arms and legs of lymphedema patients.

After several years of reporting, the literature falls silent from 1994 until 1999 when the department of Cardiovascular Surgery of the University of Tokushima, Japan published a very brief followup item.

I have been unable to find any documentation on why the research was halted for several years; nor any explanation as to the mechanism of why the treatment produced some positive results.

Dr. Stanley Rockson, a well respected lymphedema doctor in the United States mentions the treatment only very briefly in his paper, Treatment Options published in 2000.

Here for your review are the available abstracts on the subject.


Investigation of the mechanism of lymphocyte injection therapy in treatment of lymphedema with special emphasis on cell adhesion molecule (L-selectin).

Lymphology. 1999 Dec;32(4):151-6.

Ogawa Y, Yoshizumi M, Kitagawa T, Kitaichi T, Katoh I, Hisaeda H, Himeno K.

Department of Cardiovascular Surgery, School of Medicine, University of Tokushima, Japan.

We previously employed intraarterial lymphocyte injection therapy in conjunction with standard non-operative treatment of peripheral lymphedema of various etiologies. In this study, we further evaluated the clinical outcome of this therapy in 46 patients with unilateral lymphedema of the extremities. The results showed combined therapy (lymphocyte injection with compression) was effective in 74% (34 of 46 patients) with dramatic reduction in lymphedema in 37% (17 of 46 patients). In the most recent 5 patients treated, we examined the expression of cell adhesion molecule of the lymphocytes (L-selectin) before, during and after lymphocyte injection therapy to study the putative pathomechanism of this treatment method. The expression of L-selectin, a lymphocyte-specific adhesion molecule, increased in the autologous lymphocytes obtained by a blood cell separator and in the lymphocytes from the peripheral blood after injection. Moreover, the lymphocyte fraction, which was positive for L-selectin and negative for CD3, a T-cell marker, decreased after lymphocyte injection. We postulate that the lymphocytes of L-selectin (+) and CD (-) remain in the affected swollen limb and play a role in an ill-defined immunologic responsiveness that potentiates reduction in edema.


Quantitative evaluation of intraarterial lymphocyte injection therapy for lymph edema using MR imaging.

Acta Radiol. 1994 Sep;35(5):405-8.

Harada M, Amano Y, Matsuzaki K, Hayashi Y, Nishitani H, Yoshizumi M, Yoshida O, Katoh I.
Department of Radiology, School of Medicine, University of Tokushima, Japan.

Five patients with unilateral leg lymph edema had intraarterial injections of lymphocytes in the affected leg with consequent improvement in 3. To assess the degree of lymph edema, T2 and intensity ratio between the 2 legs in STIR images were used. Mean and SD of T2 values in the subcutaneous tissue were measured using a triple echo sequence and found larger on the edematous side than in the opposite extremity. The mean T2 shortening obtained after the lymphocyte therapy correlated well with the reduction of limb circumference. Mean T2 reflects the fluid content, and SD of T2 the fluid distribution in the subcutaneous tissue. The degree of lymph edema and the effect of therapy can be evaluated quantitatively by measuring the value of the T2 relaxation time.

PMID: 8086242 [PubMed - indexed for MEDLINE] ... med_docsum


Autologous lymphocyte therapy for experimental canine lymphoedema: a pilot study.

Aust N Z J Surg. 1994 May;64(5):332-7.

Knight KR, Ritz M, Lepore DA, Booth R, Octigan K, O'Brien BM.
Microsurgery Research Centre, St Vincent's Hospital, Melbourne, Victoria, Australia.

Obstructive lymphoedema, an accumulation of protein-rich fluid in interstitial spaces, was created in five dogs by a combination of the irradiation of one groin and subsequent surgical ablation of any remaining lymphatics. The lymphoedema was stable for up to 2 years. The aim was to test the efficacy of intra-arterial injection of autologous lymphocytes as a therapy for lymphoedema. The hypothesis was that cytokines produced by lymphocytes mediate proteolysis by macrophage proteinases in the lymphoedematous limb to remove the excess protein and relieve the oedema. A concentrated lymphocyte-rich preparation was isolated from blood by the Ficoll-Paque method. These preparations were injected into the femoral artery four times at approximately 4 weekly intervals. Three months after the first injection of lymphocytes, lymphoedematous limbs showed a marked 69% reduction in the mean excess circumferences compared with opposite control limbs. After treatment, skin thickness and hydroxyproline content (both measures of fibrosis) as well as water content (a measure of oedema) had reduced significantly. In specimens of interstitial fluid and in skin homogenates acidic proteinase activity increased and the protein concentration decreased significantly compared with controls. It is concluded that increased proteolysis, possibly due to activated macrophages recruited to the lymphoedematous limb, may partly explain these results.

PMID: 8179530 [PubMed - indexed for MEDLINE] ... med_docsum


Intraarterial infusion of autologous lymphocytes for the treatment of refractory lymphoedema. Preliminary report.

Eur J Surg. 1994 Feb;160(2):105-9.

Nagata Y, Murata R, Mitsumori M, Okajima K, Ishigaki T, Ohya N, Fujiwara K, Abe M, Kumada K.
Department of Radiology, Kyoto University Hospital, Japan.

OBJECTIVE: To evaluate the results of the treatment of lymphoedema by intra-arterial infusion of autologous lymphocytes.

DESIGN: Open study.

SETTING: University Hospital. SUBJECTS: 13 patients with refractory lymphoedema.

INTERVENTIONS: Lymphocytes were separated from the patient's own blood using a blood cell separator; about 100 cc of lymphocyte dominant blood separated from this blood was immediately infused into the proximal artery of the affected limb. Infusion was practiced once a week, and repeated 4 to 6 times.

MAIN OUTCOME MEASURES: Change in size of the affected limb (defined as the difference between the affected limb and the normal limb after treatment), and softening of the edema (measured with a tension gauge).

RESULTS: In all 13 patients there was softening of the affected hard limb followed by a reduction in the size of the limb (mean 64%), and the ache and sensation of heat in the limb lessened. The reduction in size was maintained in 9 of the 13 patients for three months, despite returning to their normal activities.

CONCLUSION: Intra-arterial infusion of autologous lymphocytes is a promising treatment for refractory lymphoedema.

PMID: 8193206 [PubMed - indexed for MEDLINE] ... med_docsum


Reduction in arm swelling and changes in protein components of lymphedema fluid after intraarterial injection of autologous lymphocytes.

Lymphology. 1993 Dec;26(4):169-76

Egawa Y, Sato A, Katoh I, Natori Y, Monden Y.
Department of Surgery, School of Medicine, University of Tokushima, Japan.

The intraarterial arm injection of freshly isolated autologous lymphocytes to a patient with upper extremity secondary lymphedema brought about a rapid and remarkable reduction in arm swelling. The protein components in the edema fluid were analyzed by two-dimensional electrophoresis before and after lymphocyte injection. We observed the appearance of a novel protein spot, with an isoelectric point of 6.5, in an electropherogram as early as 30 minutes after the lymphocyte injection. Immunoblotting using antibody against human total serum proteins suggested that the novel protein was not derived from the serum. Because incubation in vitro of the lymphedema fluid with the isolated lymphocytes produced a new protein spot, corresponding to the novel protein observed in vivo, we suspect that the novel protein originated from limited hydrolysis of a unique protein present in the arm edema fluid. Significance of the novel protein and the role of limited proteolysis after lymphocyte injection in the management of lymphedema are examined.

PMID: 8121194 [PubMed - indexed for MEDLINE] ... med_docsum


Intraarterial lymphocyte-injection therapy for lymphedema of the leg: an examination using indium-111 oxine labeled autologous lymphocytes.

Tokushima J Exp Med. 1992 Dec;39(3-4):123-6.

Yoshizumi M, Katoh I, Yoshida O, Kitagawa T, Nishimura T, Fukumura Y, Matsumoto T, Nishitani H.
Department of Cardiovascular Surgery, University of Tokushima, Japan.

A 58-year-old female patient with lymphedema of the left leg was treated by repeated intraarterial lymphocyte-injection therapy. To elucidate whether the injected lymphocytes act at the affected site of the leg, we examined the distribution of the In-111 oxine labeled lymphocytes injected into the proximal artery to the affected leg in comparison with the distribution in the other, healthy, leg. The radioactivity of the affected leg was almost two times higher than that of the healthy leg during the first 30 min after injection, and it remained higher even after 24 hours. The circumference of the affected leg of the patient decreased steadily during her hospital stay. These results, together with the clinical findings, suggest that some of the intraarterially-injected lymphocytes remained in the affected leg at least 24 hours and might play some role in reducing the volume of lymphedematous fluid.

PMID: 1295129 [PubMed - indexed for MEDLINE] ... med_docsum


A method for following human lymphocyte traffic using indium-111 oxine labelling.

Clin Exp Immunol. 1981 Mar;43(3):435-42.

Wagstaff J, Gibson C, Thatcher N, Ford WL, Sharma H, Benson W, Crowther D.
A method is described whereby large numbers of human lymphocytes are separated from peripheral blood and labelled in vitro with indium-111 oxine. Following autologous reinjection, the distribution within the body is followed by means of serial blood samples, surface-probe counting and gamma camera imaging. The distribution of radioactivity following reinjection of heat-damaged labelled lymphocytes and free indium-111 oxine is different from that of 'normal' lymphocytes. The results suggest that the separation and labelling procedure does not cause significant physical damage to the lymphocytes The importance of restricting the specific lymphocyte activity to 20-40 microCi per 10(8) cells in order to minimize radiation damage to the lymphocytes is emphasized. Good resolution of lymphoid structures is obtained using gamma camera imaging and the changes recorded in organ distribution correlate well with data from animal models of lymphocyte migration. Thus, indium-111 oxine labelling of human lymphocytes provides a non-invasive method whereby the migratory properties of human lymphocytes can be followed.

PMID: 7285387 [PubMed - indexed for MEDLINE] ... med_docsum


Intraarterial lymphocytes injection for treatment of lymphedema.

Jpn J Surg. 1984 Jul;14(4):331-4

Katoh I, Harada K, Tsuda Y, Fujishima N, Egawa Y, Sugama M, Inoue K.
We noted a marked improvement of lymphedema in a patient with recurrence of cancer 3 years after amputatio recti and with post-thrombotic syndrome of the leg, as the result of injection of a suspension of lymphocytes administrated as therapy against advanced cancer. Subsequently lymphocytes-injections were given 39 times to 7 patients with lymphedema of one limb, of various causes. A suspension of lymphocytes was injected repeatedly into the proximal artery of the affected limb. In one patient, lymphocytes were injected 4 times at intervals of 1 or 3 weeks. In most cases, this injection resulted in a marked reduction in the swelling of the affected limb and improvement was seen for several weeks or months. In all cases, there was a marked, continuous softening of the tissue.

PMID: 6492508 [PubMed - indexed for MEDLINE] ... med_docsum

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