The findings were presented at the 2011 American Society of Hematology (ASH) meeting in San Diego last month.

In France, chemotherapy is typically administered in a hospital. However, the French National Health Service allows home administration of some chemo­therapy treatments after the first treatment cycle.

A group of French researchers, therefore, sought to investigate if Vidaza (azacitidine) could be safely administered at home.

Sixty-eight patients, including 51 with myelodysplastic syndromes (MDS), volunteered for this study after receiving their first cycle of chemotherapy in the hospital. Forty-eight of the study patients were treated with Vidaza.

The study participants were divided into two groups. One group continued to receive all doses of Vidaza administered at a hospital.  The other group received Vidaza at a hospital the first day of every treatment cycle, but all other doses of Vidaza in the treatment cycle were administered at home.

The researchers compared the number of treatment cycles the patients were able to complete, the dosage patients were able to tolerate, and problems with administration for both patient groups.

Results showed that over the 18-month study period, both groups received a similar median number of treatment cycles.

The two groups also experienced similar side effects, delays between treatment cycles, and hospitalizations between cycles.

The researchers also observed a high level of patient satisfaction in the home administration group.

They reported that all patients in the home administration group agreed to continue at-home treatment.

In some cases, home administration of Vidaza was not possible because of infection, low blood cell counts, or drug availability.

According to the researchers, further randomized studies are planned to compare the quality of life between patients receiving chemotherapy in the hospital or at home.

For more information, please see abstract 1719 at the ASH 2011 meeting website.

Treatment with a combination of Vidaza (azacitidine) and Revlimid (lenalidomide) has previously been shown to be effective in higher-risk myelodysplastic syndromes (MDS) patients with or without chromosomal abnormalities.

The two new studies on the combined use of Vidaza and Revlimid were presented at the 2011 American Society of Hematology (ASH) meeting last month.

Phase 2 Trial: Simultaneous Treatment With Vidaza And Revlimid

Dr. Mikkael Sekeres of the Cleveland Clinic presented results from a Phase 2 trial showing high efficacy of the Vidaza-Revlimid combination therapy in higher-risk MDS patients who had not been previously treated with either drug.

The study included 36 patients with a median age of 68 years. They had been diagnosed a median of eight weeks before signing up for the trial.

The patients were treated with 75 mg/m² of Vidaza daily for the first five days of a 28-day treatment cycle.  They also received 10 mg of Revlimid daily for the first 21 days of the treatment cycle.

Patients could receive a maximum of seven cycles of combination therapy, after which they could choose to continue treatment with Vidaza alone.  The study participants received a median of five treatment cycles.

Overall, 72 percent of patients responded to the Vidaza-Revlimid combination treatment after a median of three months: 42 percent of patients achieved a complete response lasting for a median of 16 months, plus 28 percent of patients showed improved blood cell counts.

The patients who experienced a complete response had a median overall survival of 27 months; 50 percent of these patients progressed to acute myeloid leukemia at a median of 20 months.

The most common severe side effects included low white blood cell counts with fever (31 percent), heart problems (11 percent), lung problems (11 percent), infections (8 percent), blood clots (6 percent), and central nervous system bleeding (6 percent).

Three patients (8 percent) died during the trial.

Phase 1 Trial: Vidaza Treatment Immediately Followed By Revlimid Treatment

Results of a recent Phase 1 study of Vidza followed by high-dose Revlimid were summarized in a poster presentation. The results show that the combination may be effective and safe in certain higher-risk MDS patients.

This study included 28 patients with MDS, chronic myelomonocytic leukemia, or acute myeloid leukemia.

Study participants could be any age if they were unresponsive to their previous treatment (22 patients).  Patients were also accepted if they were older than 60 years and had not received prior treatment for their condition (six patients).  The median age of the study participants was 65 years.

The patients received 75 mg/m² Vidaza intravenously (in the vein) for the first five days of a 28-day treatment cycle.

They then received 10 mg to 75 mg of Revlimid starting on the sixth day of the treatment cycle for five consecutive days or 75 mg of Revlimid for ten consecutive days

The study participants completed a median of 1.5 treatment cycles.

The researchers were able to evaluate five of the six patients who had not received prior treatment; 60 percent of these patients achieved a complete response.  They were treated with 25 mg or 50 mg of Revlimid for five consecutive days following Vidaza treatment.

None of the previously treated patients responded to the sequential treatment; 47 percent maintained stable disease.

The most common side effects included fatigue, loss of appetite, constipation, rash, fever, and weight loss.

No dose-limiting side effects were observed, so the maximum tolerable Revlimid dose was not determined.

One of the patients who received 75 mg of Revlimid for ten days after Vidaza treatment died.  The remaining six patients in this treatment group continued treatment without any severe side effects.

A Phase 2 trial is currently under way to study the effects of 50 mg of Revlimid for ten consecutive days after Vidaza treatment in 40 newly diagnosed patients.

For more information, please see abstract 607 and abstract 2613 at the ASH 2011 meeting website.

The study authors found that the efficacy and safety of the combination therapy were similar to those of other treatment regimens commonly tested in clinical trials.

They concluded that their findings support treatment for patients who are ineligible for clinical trials, and they suggested that current eligibility criteria for Phase 1/2 clinical trials be reexamined.

Dr. Guillermo Garcia-Manero of the MD Anderson Cancer Center in Houston presented these findings at the 2011 American Society of Hematology (ASH) conference in San Diego earlier this month.

In order for a patient to be eligible to participate in most clinical trials for myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML), the patient must display acceptable overall health, kidney function, and liver function. Patients also cannot have any other co-existing diseases.

Researchers at the MD Anderson Cancer Center found that MDS and AML patients who are not eligible for clinical trials have a median survival of less than 60 days if they do not receive treatment.

In the present study, the researchers aimed to evaluate the influence of therapy on survival outcomes for MDS and AML patients who do not qualify to participate in clinical trials. All 30 patients in the study were treated with Vidaza (azacitidine) and Zolinza (vorinostat) for a median of 3.5 cycles. The researchers chose this combination therapy because they consider it to be safe and it has shown significant activity in both MDS and AML patients.

Vidaza is approved by the U.S. Food and Drug Administration (FDA) as a treatment for patients with MDS. Zolinza also is approved by the FDA, but as a treatment for specific kind of lymphoma. It can be prescribed, however, by a physician as a treatment for other conditions – such as MDS – if the physician feels there is sufficient evidence to justify such use of the drug.

The median patient age in the MD Anderson study of the Vidaza-Zolinza combination treatment was 74 years, and 53 percent of the patients had MDS. In addition, 53 percent had another type of cancer. The remaining patients had another co-existing disease, including chronic liver disease, liver failure, heart dysfunction, chronic bronchitis and emphysema, or poor overall health.

The overall response rate was 30 percent, with 27 percent achieving a complete response. Half of the patients who did not register a response to the treatment regimen nevertheless had stable disease for more than eight weeks.

The median survival was seven months, and 80 percent of patients survived longer than 60 days.

Thirty percent of the patients are still alive as of the date the trial data were analyzed in preparation for the ASH meeting. All of the deaths during the study were due to progression of the patient’s primary disease.

The researchers pointed out that the therapy was well tolerated since only one patient (3 percent) developed a serious, non-blood-related side effect (nausea and vomiting).

For more information, please see abstract 608 at the ASH 2011 meeting website.

In addition, the study authors found that patients who had a complete response to the combination therapy experienced significantly longer overall survival than those who did not.

Dr. Thomas Schroeder of Heinrich Heine University in Duesseldorf, Germany, presented the clinical trial findings at the 2011 American Society of Hematology (ASH) conference in San Diego last week.

In patients with myelodysplastic syndromes (MDS), relapse after stem cell transplantation is associated with a poor disease prognosis.

Previous research has shown that MDS and acute myeloid leukemia (AML) patients who relapse after transplant often respond to treatment with Vidaza (azacitidine).

Some retrospective studies also have shown encouraging results for combination therapy involving Vidaza and donor lymphocyte infusion.

Donor lymphocyte infusion, often abbreviated DLI, is a procedure in which a stem cell transplant patient receives an infusion of donated white blood cells. The cells usually are donated by the original stem cell transplant donor.

In the present study, German researchers evaluated the efficacy and safety of Vidaza and donor lymphocyte infusion in MDS and AML patients. The combination therapy was used as a salvage therapy after the patients relapsed following transplantation.

Of the 30 patients included in the study, 92 percent had AML and 8 percent had MDS. At a median of 160 days after transplant, all patients experienced relapse.

Patients received 100 mg/m² of Vidaza daily on days 1 through 5 of a 28-day treatment cycle followed by donor lymphocyte infusion after every second treatment cycle.

Patients received a median of three treatment courses of Vidaza, and 73 percent of patients received a donor lymphocyte infusion, with a median of one infusion.

Overall, 47 percent of the patients responded to the treatment, with 23 percent achieving a complete response and 7 percent achieving a partial response. Of the patients who achieved a complete response, 71 percent maintained long-term complete response (median of 605 days) without any additional therapies.

At a median follow-up period of 645 days, 17 percent of the patients are still alive. The median overall survival time is 117 days. Patients who achieved a complete response to the trial regimen had significantly longer survival times than those who did not (not yet reached versus 83 days).

The primary causes of death were progressive disease (40 percent), infection (13 percent), and bleeding (7 percent). Five patients underwent a second stem cell transplant, but all have died.

Graft-versus-host disease, a common transplant-related complication in which the donor stem cells recognize the recipient’s immune system as foreign and attack it, occurred in 42 percent of patients (37 percent acute, 5 percent chronic).

All patients in the trial experienced serious to life-threatening low blood cell counts, but only 37 percent were considered to be treatment-related. Other common side effects included infection and bleeding.

For more information, please see abstract 656 at the ASH 2011 meeting website.

Dr. Thorsten Braun of the Avicenne Hospital in Bobigny, France, presented the trial results during an oral session at the 2011 meeting of the American Society of Hematology (ASH) earlier this week.

Patients who fail Vidaza (azacitidine) treatment typically have poor prognoses (see the related Beacon news).

Previous studies have shown that Clolar (clofarabine), a drug currently approved for the treatment of acute lymphoblastic leukemia, can be effective in MDS patients who have failed treatment with Vidaza (see the related Beacon news).  However, the treatment has been associated with significant side effects.

In the current study, the authors examined whether lower doses of Clolar and an extended, alternate-day treatment schedule would also be effective and safe in this patient population.

The study enrolled 19 patients from November 2009 to July 2011.  Nine patients received 5 mg/m² of Clolar, and ten patients received 7.5 mg/m² of Clolar.

Patients from each Clolar dosage group were treated either daily for the first five days of a 28-day cycle (standard schedule) or on days 1, 3, 5, 8, and 10 of the 28-day cycle (extended, alternate day schedule).

After one treatment cycle, six patients (32 percent) responded to treatment; two of them were treated with 5 mg/m² of Clolar on the extended, alternate day schedule and four with 7.5 mg/m² of Clolar.

Of the two patients treated with 5 mg/m² of Clolar, one experienced a complete bone marrow response.  The other patient had improved platelet and red blood cell counts.

Of the four patients treated with 7.5 mg/m² of Clolar, two treated on the standard schedule achieved a com­plete bone marrow response including improved platelet and red blood cell counts. The other two patients were treated using the extended, alternate day schedule.  One patient achieved a complete response, while the other patient achieved a partial response.

Three patients treated with 5 mg/m² of Clolar and four patients treated with 7.5 mg/m² of Clolar were hospitalized for fever or bleeding.

Of the patients treated using the standard schedule, one patient treated with 5 mg/m² of Clolar died at the end of the second treatment cycle, and one patient treated with 7.5 mg/m² of Clolar experienced prolonged low platelet counts.

None of the patients treated on the extended, alternate day schedule experienced any severe side effects after the first cycle of treatment.

For more information, please see abstract 609 at the ASH 2011 meeting website.

Day 3

Monday was a busy day in terms of presentations related to myelodysplastic syndromes (MDS).  There were several sessions with oral presentations throughout the day and a poster session in the evening.

The day began with a session about genetic alterations in MDS.  During the session, researchers presented the latest findings on how alterations in patients’ genes and proteins may influence their MDS. In a session that ran at the same time, researchers presented findings about late complications in stem cell transplants.

The talks in the afternoon focused on treatment options for MDS patients. Some of the highlights are described here.

Dr. Mikkael Sekeres from the Cleveland Clinic presented final results from a Phase 2 trial that investigated a combination treatment of Vidaza (azacitidine) and Revlimid (lenalidomide) in high-risk MDS patients. Results showed that the combination treatment was effective and safe; 72 percent of patients responded to the treatment, with 42 percent achieving a complete response. The most common serious side effects were fever (31 percent), heart-related (11 percent), and lung-related (11 percent) (abstract).

Dr. Guillermo Garcia-Manero from the MD Anderson Cancer Center presented results from a trial of another Vidaza-based combination therapy. In this Phase 2 study, Vidaza was tested in combination with Zolinza (vorinostat), a so-called “HDAC inhibitor” that is currently approved for the treatment of a certain type of lymphoma, in patients who are not eligible for clinical trials. The researchers found that the combination of Vidaza and Zolinza was active and well tolerated in this patient population; 30 percent of patients responded to treatment and no major side effects were observed (abstract).

In addition, results were presented from a Phase 1/2 dose-finding study of low-dose Clolar (clofarabine) in high-risk MDS and acute myeloid leukemia (AML) patients who had failed Vidaza treatment. The researchers tested different dosing schedules and found that an every-other-day dosing schedule may work best in this patient population (abstract).

Presentations about the stem cell microenvironment in MDS were given during an oral presentation session late in the afternoon.

In the evening, the authors of poster research summaries were available to discuss their results.  There were posters about research into current MDS treatments as well as new drugs that are under development. Some of the highlights are described below.

In a Phase 1 trial, researchers investigated the safety of oral Dacogen (decitabine) in MDS patients. Patients received varying doses of Dacogen orally on the first day of the treatment cycle, followed by a one-hour infusion of 20 mg/² Dacogen on days 2 through 5 of a 28-day treatment cycle. The researchers found that the safety profile of oral Dacogen was similar to that of intravenous Dacogen (abstract).

Results of a Phase 1/2 trial suggest that oral Estybon (rigosertib, ON 01910.Na) is active and well tolerated in MDS patients. In the Phase 1 part of trial, researchers tested different dosing schedules and determined that 560 mg of Estybon twice daily was the maximum tolerated dose, which is now being investigated in the Phase 2 part of the trial (abstract).

German researchers investigated the efficacy of Revlimid as maintenance therapy in MDS and AML patients with chromosomal abnormalities who had undergone a stem cell transplant. After four cycles of treatment, 80 percent of patients discontinued treatment because they developed graft-versus-host disease, a transplant-related complication. The researchers speculated that Revlimid may have contributed to the onset of graft-versus-host disease (abstract).

French researchers conducted a retrospective analysis to determine the effect of chronic graft-versus-host disease on outcome in patients who received low-dose chemotherapy in combination with a donor stem cell transplant. Chronic graft-versus-host disease is a transplant-related complication that develops 100 days or more after the transplant. The researchers found that mild to moderate forms of the complication were associated with better overall survival than severe forms or not developing the complication at all (abstract).

Israeli researchers looked at an issue that often occurs during treatment of MDS with Vidaza.  Despite its effectiveness in high-risk patients, Vidaza is often associated with fever and infections. Results of a retrospective analysis by the Israeli researchers indicate that transfusion dependency prior to the first Vidaza treatment cycle, and low platelet counts (lower than 20,000) prior to each treatment cycle, may be the main risk factors for developing infections during Vidaza therapy (abstract).

Day 4

Yesterday was the final day of the ASH annual meeting. The MDS portion of the conference concluded in the morning with a session on advances in prognostic models for MDS, which are particularly relevant for physicians treating MDS.

Researchers from the MD Anderson Cancer Center in Houston introduced a new prognostic model for patients with therapy-related MDS that predicts overall and leukemia-free survivals. They argue that their model may help in the development of risk-adapted treatment strategies (abstract).

Results from another study were presented that validates a newly developed prognostic scoring system for low-risk MDS patients. In an independent patient population, researchers were able to identify low-risk MDS patients that are at an increased risk for disease progression with the help of the new model (abstract).

French researchers assessed the prognostic value of the revised International Prognostic Scoring System (IPSS), which was recently introduced, in MDS patients that were treated with Vidaza. They found that the revised scoring system could predict the response to Vidaza treatment but it did not find a difference in overall survival between intermediate-risk and poor-risk patients. According to the current IPSS model, intermediate-risk and poor-risk patients have significantly different overall survival times. The researchers suggested that more specific prognostic scoring systems may be necessary for patients treated with Vidaza (abstract).

Day 1

Saturday started off with an education session on myelodysplastic syndromes (MDS) that consisted of three talks. The program was repeated in the afternoon.  

The day ended with a large poster session, during which study results from hundreds of blood disorder-related studies were displayed on big posters attached to boards throughout the exhibition hall. Many posters were accompanied by a presenter or printouts of the poster for attendees to take with them.

There were a number of posters about current MDS treatments as well as new drugs that are under development. Some of the highlights are described below.

French researchers conducted a small study to see if home administration of Vidaza (azacitidine) is possible. They argued that home administration would significantly improve the quality of life of MDS patients. They found that home administration was safe and feasible. A similar median number of cycles and treatment delays were observed between patients who received Vidaza at the hospital and those who received Vidaza at home. Side effect levels and rates of hospitalization were also similar between the two groups (abstract).

Preliminary results from a Phase 1/2 study suggest that the HDAC inhibitor panobinostat, which is being developed by Novartis, is well tolerated and shows some clinical activity in combination with Vidaza in previously untreated MDS patients. The maximum tolerated dose was 30 mg of panobinostat in combination with a 5-day Vidaza schedule of 75 mg/m² daily (abstract).

Results of an analysis of five trials involving Revlimid (lenalidomide) for the treatment of MDS did not show any clear evidence that Revlimid is associated with an increased risk of secondary cancers in patients with lower-risk MDS with or without del(5q). According to the study authors, the rate of invasive secondary cancers among patients treated with Revlimid was what would be expected among persons in this age group (abstract). Concerns about an increased risk of secondary cancers were first raised at last year’s ASH meeting when study results showed an increased rate of secondary cancers in multiple myeloma patients who had received Revlimid as maintenance therapy (see related news).

Results of a small French study showed that Nplate (romiplostim), which is currently approved to increase platelet levels in patients with chronic immune thrombocytopenia, may be a treatment option for patients who experience low platelet counts after donor stem cell transplantation. Low platelet counts increased in all seven study participants who received Nplate therapy (abstract).

Results from a Korean analysis showed that for patients who receive Vidaza or Dacogen (decitabine) before donor stem cell transplantation, outcomes after stem cell transplantation were better for patients who started the transplant process while still responding to Vidaza or Dacogen than for patients who had progressed. These findings suggest that stem cell transplantation should be initiated while the patient is still responding to Vidaza or Dacogen therapy (abstract).

Treatment with Vidaza or Dacogen may also be a good treatment alternative for patients who are older or cannot tolerate donor stem cell transplantation. When researchers from the MD Anderson Cancer Center in Texas retrospectively compared outcomes for patients who received treatment with Vidaza or Dacogen to patients with similar characteristics who had received a stem cell transplant, they found that the median survival was 26 months for patients receiving a stem cell transplant and 25 months for patients treated with Vidaza or Dacogen. The eight-year overall survival rates were 24 percent and 23 percent, respectively (abstract).

Another analysis from the National Institutes of Health looked at the role of immunosuppressive therapy in MDS. In some types of MDS, the immune system attacks the bone marrow and prevents it from making healthy blood cells. As a result, scientists have recently proposed immunosuppressive therapy as a possible treatment for MDS. This therapy employs drugs that reduce the immune system’s response, thereby allowing the bone marrow to produce more blood cells. The analysis showed that the overall response rate to immunosuppressive therapy was 41 percent. Response rates were higher in patients younger than 60 years old and patients with lower-risk MDS.  The number of immature blood cells and the duration of transfusion dependence did not affect response (abstract).

Day 2

Yesterday was the second full day of the ASH annual meeting. The MDS sessions included a series of talks in the afternoon and a poster session in the evening.

The talks in the afternoon focused on treatment options for MDS patients.

Results of a Phase 1/2 extension study showed that Nplate improved platelet counts in 37 percent of lower-risk MDS patients. However, Nplate also led to an increase in immature blood cell counts and increased risk of progression to acute myeloid leukemia (AML), so the study was discontinued earlier this year (abstract).

After that, results results from a Phase 1 trial were presented showing that the investigational drug ARRY-614 has clinical activity in lower-risk, relapsed/refractory MDS patients. The goal of the study was to determine the maximum tolerated dose of ARRY-614. At the highest dose tested, 38 percent of patients showed blood cell count improvements. The most common side effects were rash and diarrhea (abstract).

In addition, results from a retrospective analysis were presented showing that Revlimid extends overall survival and is not associated with an increased risk of progression to AML in lower-risk, transfusion-dependent MDS patients with the chromosomal abnormality del(5q). The two- and five-year rates of AML progression were 7 percent and 23 percent for patients who received Revlimid, compared to 12 percent and 20 percent for patients who did not receive Revlimid. Median time to AML progression has not been reached for this patient group. The two- and five-year overall survival rates were 90 percent and 54 percent for patients who received Revlimid, compared to 74 percent and 41 percent for patients who did not receive Revlimid. Median overall survival was 5.2 years for patients who received Revlimid, compared to 3.8 years for patients who did not receive Revlimid (abstract).

The evening once again featured a poster session that included additional results from many MDS-related clinical trials. Some of the results are highlighted below.

In one study, researchers tested the combination of the HDAC inhibitor belinostat, which is being developed by the pharmaceutical company Spectrum Pharmaceuticals, in combination with Velcade (bortezomib) in patients with AML and MDS. They found that the combination was tolerated and showed modest activity. The maximum tolerated dose has not been reached yet (abstract).

In another study, researchers investigated the efficacy of Vidaza in MDS patients with the chromosomal abnormality del(5q) who had previously failed Revlimid treatment. They found that the response rates were similar to those reported in patients without the chromosomal abnormality, which led the researchers to conclude that Vidaza may be an effective salvage treatment for this patient population (abstract).

In a Phase 1 study, researchers evaluated Telintra (ezatiostat hydrochloride) in combination with Revlimid in lower-risk MDS patients with the chromosomal abnormality del(5q). Forty-three percent of patients responded at the highest dose recommended for further testing. According to the researchers, Telintra may enhance Revlimid’s efficacy and the combination was well tolerated (abstract).

In another Phase 1 trial, researchers tested quick, sequential administration of Vidaza and Revlimid because they hypothesized that this approach may be particularly useful for patients with high-risk MDS and AML. Patients received 75 mg/m² Vidaza on days 1 to 5, followed by Revlimid starting on day 6 for five to ten days of a 28-day treatment cycle. Different Revlimid doses were tested, but the maximum tolerated dose has not been reached yet. So far, 60 percent of previously untreated patients have achieved a complete response (abstract).

Transfusion dependency may be an important factor for the prognosis of MDS patients. When European researchers retrospectively analyzed data from an MDS and AML registry, they found that patients who required more than 20 units of transfusions had the highest death rate (30 percent), compared to patients who did not need transfusions (5 percent) (abstract).

When French researchers investigated the impact of incorporating the immunosuppressive therapy agent antithymocyte globulin (ATG) into the preparative treatment for donor stem cell transplantation, they found that ATG resulted in a lower rate of acute graft-versus-host disease, a common transplant-related complication. At the same time, ATG did not negatively affect relapse rates nor survival (abstract).

The most common side effects were low blood cell counts, which required close monitoring. However, the study authors concluded from these results that the side effects were acceptable when compared to conventional chemotherapy, which is often ineffective and intolerable in high-risk patients.

Previous research has shown that the combination therapy of Vidaza (azacitidine) and Revlimid (lenalidomide) is effective and safe in patients with higher-risk myelodysplastic syndromes (MDS) (see related Beacon news).

Vidaza destroys rapidly dividing cells by removing methyl groups from DNA. Revlimid promotes cell death by preventing the growth of new blood vessels needed for tumor survival.

Researchers have recently proposed that the complementary mechanisms of Vidaza and Revlimid may produce additional benefits not seen in single-agent therapy.

In the present study, French researchers report their experience with Vidaza and Revlimid as a first-line therapy in eight patients with high-risk MDS or acute myeloid leukemia (AML) with chromosomal abnormalities. All of the patients had three or more abnormalities in their chromosomes, which is called a complex karyotype. The median patient age was 66.5 years.

The median time from diagnosis to the start of treatment was 3.5 months.

Five patients received 75 mg/m² of Vidaza on days 1 through 5, and three patients received 75 mg/m² on days 1 through 7 of a 28-day cycle. In addition, the patients received 10 mg of Revlimid on days 1 through 21. One patient received 5 mg of Revlimid.

Six of the eight patients responded to treatment: three with a complete response and three with a partial response. The two remaining patients experienced disease progression during treatment.

The initial response occurred at a median of 10 weeks after the treatment started. Four of the six responders relapsed at a median of 12 weeks after their initial response. The other two responding patients are still alive and in complete remission. Both patients received a donor stem cell transplant.

The median overall-survival and progression-free survival were 15 months and 9.5 months, respectively.

The major observed side effects were low blood cell counts. Seven of the eight patients experienced severe to life-threatening low platelet counts. Five patients developed severe to life-threatening low white blood cell counts, which often resulted in blood poisoning and, in two cases, hospitalization in the intensive care unit.

Five of the eight patients died. Two patients died because their disease was resistant to treatment. After initially responding to treatment, three patients died from disease progression.

For more information, please refer to the article in Leukemia (abstract).

Free Conference For MDS Patients And Their Families – On November 12, the MDS Foundation will host a free one-day conference for MDS patients and their families in Philadelphia. The conference will start at 10 a.m. with a patient support group discussion. In the afternoon, new therapies and treatment options for MDS will be presented and discussed.  Complimentary breakfast and lunch will be served. For more information, please see the MDS Foundation website.

Webinar: MDS And Health Insurance Coverage – On November 17, the Aplastic Anemia & MDS International Foundation (AA&MDSIF) is hosting a webinar to explain health insurance coverage rules to MDS patients and their families. The webinar, which starts at 3 p.m. ET, will also include information about prescription and co-pay assistance programs that may be of interest to MDS patients. Participants will have the opportunity to ask questions at the end of the webinar. For more information or to register, please see the AA&MDSIF website.

For a more detailed listing of MDS-related events, please check the MDS Beacon Events Calendar.

The German regimen involves four days of treatment with fludarabine, amsacrine, and high-dose cytarabine followed, several days later, by a single high dose of melphalan.

The researchers investigating this regimen found that 97 percent of the patients who received it achieved complete remission within one month following their stem cell transplant.

Stem cell transplantation is currently the only potentially curative treatment available to patients with myelodysplastic syndromes (MDS).

In this procedure, patients first receive one or more drugs intended to either treat their MDS or kill off their existing stem cells, after which donor stem cells are transplanted into the patient.

Some patients also receive radiation therapy prior to transplant to help kill their existing stem cells.

There are differences of opinion, however, when it comes to what kind of preparative treatment should be used in MDS patients prior to stem cell transplantation.

In Europe, it is common for preparative treatment to include two types of therapies.

Initially, patients receive one or more rounds of “induction therapy,” which is intended to treat the patient’s MDS.  This therapy is continued until a patient’s MDS is in full or partial remission.

At that point, patients receive ”conditioning therapy,” which aims to kill off a patient’s existing stem cells.

In the U.S., physicians often skip induction therapy and instead go straight to conditioning therapy.  This approach shortens the time between diagnosis and transplant, which is considered important.

Previous research has shown that patients with higher-risk MDS experience the longest overall survival when transplants are performed soon after diagnosis.

In addition, higher-risk MDS patients often do not respond well to induction therapy, and they often get infections during induction therapy that can make them ineligible for a stem cell transplant.

An alternative approach to preparative therapy that is being explored is one that combines a brief round of induction therapy followed quickly by conditioning therapy and stem cell transplant.

One such approach that has been tried is a short induction regimen of fludarabine (Fludara), amsacrine (Amsidine), and high-dose cytarabine (Cytosar-U), followed by a conditioning regimen of low-dose total body irradiation and cyclophosphamide (Cytoxan) or busulfan (Busulfex).

According to the German authors of the current study, this quick sequential approach has shown promising results.

In the present study, the German researchers evaluated a modified version of the sequential regimen just described.  In their study, 30 previously untreated higher-risk MDS patients first received a four-day induction regimen of fludarabine, amsacrine, and high-dose cytarabine.

Then, to avoid the toxicity often seen with irradiation and cyclophosphamide or busulfan, the researchers used only high-dose melphalan (Alkeran), with or without thiotepa, as a conditioning regimen.

Following transplant, patients in the German study received granulocyte colony stimulating factor to stimulate the production of white blood cell counts. They also received Prograf (tacrolimus) and mycophenolate mofetil (Cellcept) to prevent graft-versus-host disease, a common transplant-related complication in which the donor stem cells recognize the patient’s immune system as foreign and attack it.

In addition, most of the 30 patients in the study received anti-thymocyte globulin (ATG)  for several days between induction and conditioning therapy to help prevent graft-versus-host-disease.

Patients received their transplants within a median of 134 days after diagnosis.

The German researchers found that all but one of the patients experienced improved blood cell counts after transplant. The median time for white blood cell and platelet recovery were 13 days and 17 days, respectively.

At 28 days after transplant, 97 percent of the patients were in complete remission.

At a median follow-up time of 28 months, 70 percent of patients were alive and disease-free.  Among those patients who received only melphalan during their conditioning regimen — as opposed to melphalan and thiotepa — 79 percent were alive and disease-free.

Thirteen percent of patients relapsed, but after receiving treatment with Vidaza (azacitidine) and white blood cell infusions, these patients are alive and disease-free.

Of the 30 patients included in the study, 73 percent experienced acute graft-versus-host disease, which develops within the first 100 days after the transplant; 63 percent of patients experienced chronic graft-versus-host disease, which occurs 100 days or longer after the transplant.

The most common severe, treatment-related complications were infections (53 percent), mouth ulcers (50 percent), and acute graft-versus-host disease (20 percent).

Thirty percent of patients died due to treatment-related complications. The researchers found that the risk of treatment-related death was related to the development of severe acute graft-versus-host disease.

Since the share of patients who died was particularly high among patients who received melphalan with thiotepa (67 percent), the study authors decided to remove thiotepa from the protocol early on in the trial.

For more information, please refer to the article in Biology of Blood and Marrow Transplantation (abstract).