Autolymphocyte Therapy – A Promising Adjuvant Therapy Trial

Current Use and Availability

Please Note: Currently ALT is only available as a clinical trial for prevention of recurrence in stage III and IV patients who have no evidence of disease (read on for more details on entry requirements). I think it is both relatively promising because there are some prior positive results, and especially appropriate for use as adjuvant therapy because of its minimal side effects.

What Is Autolymphocyte Therapy?

Autolymphocyte therapy (ALT) is a form of immunotherapy. It involves removal of some of your lymphocytes (white blood cells) using a process similar to a blood donation. These cells are then taken to the laboratory where they are grown in a “soup” of immune factors which stimulate the cells to make them more effective tumor killing cells and greatly increases their numbers. More than 120 billion ALT cells are prepared in the lab over a two-week period at which time they are harvested and frozen until needed for treatment. In this trial, patients receive 10 billion ALT cells once a month for 6 months and then every third month up to two years. The patient is not given any IL-2.

Side Effects of ALT

In the published literature, ALT has been said to have very minimal and generally transient side effects. On the KIDNEY-ONC mailing list we have had quite a few patients use this therapy, and three have suffered possible side effects, although in two of the three cases there is no clear evidence the problems were actually caused by the ALT treatment.

  • One patient suffered a serious infection. There is always a risk of infection or contamination with IV infusions and the use of biological products, I expect that they are extra careful about this now.
  • One patient suffered persistent fatigue after ALT. Fatigue is a common problem and there is no way to determine if the fatigue was actually caused by the ALT in an individual case.
  • One patient was diagnosed with a serious autoimmune neurological disease called Myasthenia Gravis after starting ALT. This disease is quite treatable but not curable. Myasthenia Gravis being an autoimmune disease raises the question of whether the immune stimulating effect of ALT somehow triggered the immune attack on normal tissue which causes the disease, however Myasthenia Gravis has not previously been associated with ALT therapy and again there is no way to know if ALT was the cause in any individual case. I understand from correspondence with Ann Lefever who is directing the current ALT trial, that no other cases of this disease have been reported in either any previous ALT trial or in this trial.

History of ALT and Prior Results

In a 1990 clinical trial published in the prestigious journal, The Lancet [Osband 1990], ALT doubled survival time of patients with metastatic RCC compared to no treatment, although, on the downside there were very few measurable tumor responses, and the therapy didn’t appear to offer the potential of cure. Another small, randomized trial with ALT, presented at the 1997 American Society of Clinical Oncologists (ASCO)[Sawczuk 1997] meeting and at the 1998 American Urological Association Meeting (AUA) [Sawczuk 1998], showed a prolongation of survival for patients without distant metastases but with positive regional lymph nodes. Such patients are at extremely high risk of recurrence. As far as I know this is the first positive result for adjuvant therapy for renal cell carcinoma in a randomized trial. Unfortunately, the company that was working on ALT therapy, Cytogen, formerly CellCor, cancelled the project.

Changes in ALT Therapy

ALT treatment has actually changed quite a bit since the original version published in 1990. In the original version, cells were harvested at each treatment and treated to activate them before re-infusion. Now, cells are only harvested once, and the harvested cells are stimulated and expanded in number, but are then frozen for future infusions as I described above. Among other things, this should make it a little easier on the patient. At the time of the original version, Interleukin-2 was not readily available as it is now, and so now the recipe for stimulating the cells includes adding IL-2 (Note that the IL-2 is washed away before the cells are infused – patients are not given IL-2 with this therapy!). I strongly suspect the preparation of the cells varies in other important ways from the early work, and hope to learn the details soon. One of the things I’d like to know is how the changes in treatment have been validated to make the treatment at least as potent as it was before.

The Current Trial and Preliminary Results

ALT is currently (4/02) being evaluated in a clinical trial as an adjuvant therapy at St. Luke’s Medical Center in Milwaukee. This clinical trial is open to stage III patients who have recently had a nephrectomy for RCC and who don’t have metastatic disease, and stage IV patients who are in complete remission. If you are stage IV, as long as you have No Evidence of Disease, you are potentially eligible. You should enroll in this trial within six months (and preferably three months) of your nephrectomy or achieving NED status.

According to a conversation with Dr. Ann LeFever, director of the Cellular Laboratory and one of the clinical trial investigators, an interim analysis of this ongoing trial was conducted in January 2001 and involved results from 45 patients. These survival of these patients was compared to demographically matched historical control groups of stage III and NED stage IV patients who were seen at St. Luke’s during the same time period as the clinical trial participants, but who received no adjuvant therapy, and instead were only observed for recurrence. There was a statistically significant increase in survival for stage IV patients compared to a historical control group, and for stage III patients there was also a difference that was approaching, but had not yet reached, significance. This doesn’t mean that ALT doesn’t make a difference for stage III patients. Instead, this data provided the basis for treating more stage III patients in order to define the efficacy of this treatment. Given the interim results were close to statistical significance, I think it’s likely, though not certain, that ALT makes a real difference for stage III patients. The data from the additional patients should answer the question.

Conclusions from randomized trials are considered more reliable than conclusions from historically controlled trials, which reduces the certainty about these preliminary results (In the early stages of treatment development, the use of historical controls helps researchers determine which treatments show promise and should be pursued more aggressively.). At the same time, that the current trial is not randomized has the major advantage that you are guaranteed to get the treatment if you enroll. It would seem there is very little to lose by trying ALT, since it’s almost non-toxic, there is real evidence for it, and there is no proven adjuvant therapy for RCC!

For more information

  • Contact Information
    Immunotherapy Program
    St. Luke’s Medical Center
    2900 W. Oklahoma Ave.
    Milwaukee, WI 53215
  • Entry for This Trial in my Renal Cell Cancer Evaluated Trials Database – includes patient stories and additional information.


Note: Abstracts for the adjuvant trial and some additional commentary can be found in an annotated literature search for in my Renal Cell Cancer Evaluated Trials Database

Graham S, Babayan RK, Lamm DL, Sawczuk I, Ross SD, Lavin PT, Osband ME, Krane RJ
The use of ex vivo-activated memory T cells (autolymphocyte therapy) in the treatment of metastatic renal cell carcinoma: final results from a randomized, controlled, multisite study.
Semin Urol 1993 11(1):27-34 [PubMed Abstract (will open in new window)]
Krane RJ Carpinito GA Ross SD Lavin PT Osband ME
Treatment of metastatic renal cell carcinoma with autolymphocyte therapy. Low toxicity outpatient approach to adoptive immunotherapy without use of in vivo interleukin-2.
Urology 1990 35(5):417-22 [PubMed Abstract (will open in new window)]
Lavin PT, Maar R, Franklin M, Ross S, Martin J, Osband ME
Autolymphocyte therapy for metastatic renal cell carcinoma: initial clinical results from 335 patients treated in a multisite clinical practice.
Transplant Proc 1992 24(6):3059-64 [PubMed Abstract (will open in new window)]
Osband ME, Lavin PT, Babayan RK, Graham S, Lamm DL, Parker B, Sawczuk I, Ross S, Krane RJ
Effect of autolymphocyte therapy on survival and quality of life in patients with metastatic renal-cell carcinoma
Lancet 1990 335(8696):994-8 [PubMed Abstract (will open in new window)]

Comment: This randomized controlled study of ALT for metastatic disease is the best evidence for the therapy, though it doesn't address the question of adjuvant therapy. The Lancet is one of the world's top medical journals, and publication there lends considerable crediblity to the claims.

Saidi JA, Newhouse JH, Sawczuk IS.
Radiologic follow-up of patients with T1-3a,b,c or T4N+M0 renal cell carcinoma after radical nephrectomy.
Urology 1998 Dec;52(6):1000-3. [PubMed Abstract (will open in new window)]

Comment: This paper adds a just little to our information on the prior adjuvant trial, specifically the distribution of the patients' T stages. Oddly it's the only full paper I've found that even mentions the trial, and yet even this doesn't really describe it.

Sawczuk IS
Autolymphocyte therapy in the treatment of metastatic renal cell carcinoma.
Urol Clin North Am. 1993 May;20(2):297-301. [PubMed Abstract (will open in new window)]

Sawczuk IS, Graham SD, Miesowicz F, ALT Adjuvant Study Group
Randomized, controlled trial of adjuvant therapy with ex vivo activated T cells (ALT) in T1-3a,b,c or T4N+,M0 renal cell carcinoma
Proc Am Soc Clin Oncol (ASCO Meeting Abstract) 1997 16 : Abstract 326 [You can find this abstract on the ASCO website (I can’t link directly because ASCO won’t provide a stable URL)]

Comment: You can find this abstract along with my commentary in this literature search in the Renal Cell Cancer Evaluated Trials Database

Sawczuk I, Armentrout S, Habayan R, Graham S, Hotden S, Klarnet J, Kuzel T, Leong S, Smith JA, White C
Adjuvant Autolymphocyte Therapy In The Treatment OF T 1-3a,b,c OR T 4N+M0 Renal Cell Carcinoma
Proc American Urological Association 1998 Abstract 653

Comment: You can find this abstract along with my commentary in this literature search in the Renal Cell Cancer Evaluated Trials Database

This CancerGuide Page By Steve Dunn. © Steve Dunn
Page Created: January 27, 2003, Last Updated: January 21, 2004